[Federal Register Volume 80, Number 173 (Tuesday, September 8, 2015)]
[Proposed Rules]
[Pages 53931-54061]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-21756]



[[Page 53931]]

Vol. 80

Tuesday,

No. 173

September 8, 2015

Part II





Department of Homeland Security





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6 CFR Part 46





Department of Agriculture





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7 CFR Part 1c





Department of Energy





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10 CFR Part 745





National Aeronautics and Space Administration





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14 CFR Part 1230





Department of Commerce





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15 CFR Part 27





Social Security Administration





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20 CFR Part 431





Agency for International Development





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22 CFR Part 225





Department of Justice





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28 CFR Part 46

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Department of Labor





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29 CFR Part 21





Department of Defense





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32 CFR Part 219





Department of Education





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34 CFR Part 97





Department of Veterans Affairs





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38 CFR Part 16





Environmental Protection Agency





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40 CFR Part 26





Department of Health and Human Services





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45 CFR Part 46





National Science Foundation





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45 CFR Part 690





Department of Transportation





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49 CFR Part 11





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Federal Policy for the Protection of Human Subjects; Proposed Rules

Federal Register / Vol. 80 , No. 173 / Tuesday, September 8, 2015 / 
Proposed Rules

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DEPARTMENT OF HOMELAND SECURITY

6 CFR Part 46

DEPARTMENT OF AGRICULTURE

7 CFR Part 1c

DEPARTMENT OF ENERGY

10 CFR Part 745

NATIONAL AERONAUTICS AND SPACE ADMINISTRATION

14 CFR Part 1230

DEPARTMENT OF COMMERCE

15 CFR Part 27

SOCIAL SECURITY ADMINISTRATION

20 CFR Part 431

AGENCY FOR INTERNATIONAL DEVELOPMENT

22 CFR Part 225

DEPARTMENT OF JUSTICE

28 CFR Part 46

DEPARTMENT OF LABOR

29 CFR Part 21

DEPARTMENT OF DEFENSE

32 CFR Part 219

DEPARTMENT OF EDUCATION

34 CFR Part 97

DEPARTMENT OF VETERANS AFFAIRS

38 CFR Part 16

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 26

DEPARTMENT OF HEALTH AND HUMAN SERVICES

45 CFR Part 46

RIN 0937-AA02

NATIONAL SCIENCE FOUNDATION

45 CFR Part 690

DEPARTMENT OF TRANSPORTATION

49 CFR Part 11


Federal Policy for the Protection of Human Subjects

AGENCY: Department of Homeland Security; Department of Agriculture; 
Department of Energy; National Aeronautics and Space Administration; 
Department of Commerce; Social Security Administration; Agency for 
International Development; Department of Justice; Department of Labor; 
Department of Defense; Department of Education; Department of Veterans 
Affairs; Environmental Protection Agency; Department of Health and 
Human Services; National Science Foundation; and Department of 
Transportation.

ACTION: Notice of proposed rulemaking.

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SUMMARY: The departments and agencies listed in this document propose 
revisions to modernize, strengthen, and make more effective the Federal 
Policy for the Protection of Human Subjects that was promulgated as a 
Common Rule in 1991. This NPRM seeks comment on proposals to better 
protect human subjects involved in research, while facilitating 
valuable research and reducing burden, delay, and ambiguity for 
investigators. This proposed rule is an effort to modernize, simplify, 
and enhance the current system of oversight. The participating 
departments and agencies propose these revisions to the human subjects 
regulations because they believe these changes would strengthen 
protections for research subjects while facilitating important 
research.

DATES: To be assured consideration, comments must be received at one of 
the addresses provided below, no later than 5 p.m. on December 7, 2015.

ADDRESSES: You may submit comments, identified by docket ID number HHS-
OPHS-2015-0008, by one of the following methods:
     Federal eRulemaking Portal:http://www.regulations.gov. 
Enter the above docket ID number in the ``Enter Keyword or ID'' field 
and click on ``Search.'' On the next Web page, click on ``Submit a 
Comment'' action and follow the instructions.
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions] to: Jerry Menikoff, M.D., J.D., OHRP, 1101 Wootton 
Parkway, Suite 200, Rockville, MD 20852.
    Comments received, including any personal information, will be 
posted without change to http://www.regulations.gov.

FOR FURTHER INFORMATION CONTACT: Jerry Menikoff, M.D., J.D., Office for 
Human Research Protections (OHRP), Department of Health and Human 
Services, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852; 
telephone: 240-453-6900 or 1-866-447-4777; facsimile: 301-402-2071; 
email: [email protected].

SUPPLEMENTARY INFORMATION:

Executive Summary

Purpose of the Regulatory Action
Summary of the Major Provisions of the Proposed Regulatory Actions
Estimated Costs and Benefits

I. The Rationale for Modernizing the Common Rule
    A. The Changing Nature of Research
    B. Public Comments, Expert Advice, Stakeholder Dialogue
    C. Guiding Principles for Proposed Changes
    1. Question for Public Comment
    D. Organization of the NPRM
II. Major Proposals To Modernize the Common Rule
    A. Proposed Changes to the Scope and Applicability of the 
Regulations
    1. Expanding the Definition of Human Subject to Cover Research 
With Non-identified Biospecimens (NPRM at Sec. Sec.  __.102(e) and 
__.101(b)(3)(i))
    a. NPRM Goals
    b. Current Rule
    c. ANPRM Discussion
    d. NPRM Proposal
    i. Alternative Proposals
    e. What would change in the definition of ``human subject'' 
under the primary proposal?
    f. Questions for Public Comment
    2. Explicit Exclusion of Activities From the Common Rule
    a. Exclusion of Activities That Are Deemed Not Research (NPRM at 
Sec.  __.101(b)(1))
    i. Program Improvement Activities (NPRM at Sec.  
__.101(b)(1)(i))
    (1) NPRM Proposal
    (2) Questions for Public Comment
    ii. Oral History, Journalism, Biography, and Historical 
Scholarship Activities (NPRM at Sec.  __.101(b)(1)(ii))
    (1) ANPRM Discussion
    (2) NPRM Proposal
    iii. Criminal Justice Activities (NPRM at Sec.  
__.101(b)(1)(iii))
    (1) NPRM Proposal
    iv. Quality Assurance and Quality Improvement Activities (NPRM 
at Sec.  __.101(b)(1)(iv))
    (1) NPRM Proposal
    v. Public Health Surveillance (NPRM at Sec.  __.101(b)(1)(v))
    (1) NPRM Proposal
    (2) Question for Public Comment
    vi. Intelligence Surveillance Activities (NPRM at Sec.  
__.101(b)(1)(vi))
    (1) NPRM Proposal
    b. Exclusion of Activities That Are Low-Risk and Already Subject 
to Independent Controls (NPRM at Sec.  __.101(b)(2))
    i. NPRM Goals
    ii. ANPRM Discussion
    iii. Educational Tests, Survey Procedures, Interview Procedures, 
or Observation of Public Behaviors (NPRM at Sec.  __.101(b)(2)(i))
    (1) NPRM Proposal
    (2) Questions for Public Comment
    iv. Research Involving the Collection or Study of Information 
That Has Been or

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Will Be Collected (NPRM at Sec.  __.101(b)(2)(ii))
    (1) Current Rule
    (2) ANPRM Discussion
    (3) NPRM Proposal
    (4) Questions for Public Comment
    v. Research Conducted by a Government Agency Using Government-
Generated or Government-Collected Data (NPRM at Sec.  
__.101(b)(2)(iii))
    (1) NPRM Proposal
    (2) Questions for Public Comment
    vi. Certain Activities Covered by HIPAA (NPRM at Sec.  
__.101(b)(2)(iv))
    (1) ANPRM Discussion
    (2) NPRM Proposal
    (3) Questions for Public Comment
    c. Applicability of Exclusions to the Subparts
    i. Current Rule
    ii. NPRM Proposals
    iii. Questions for Public Comment
    3. Proposed Exemptions (NPRM at Sec.  __.104)
    a. Making Exempt Research Determinations (NPRM at Sec.  
__.104(c))
    i. NPRM Goal
    ii. Current Rule
    iii. ANPRM Discussion
    iv. NPRM Proposal
    v. Questions for Public Comment
    b. Exemptions Subject to the Documentation Requirements of Sec.  
__.104(c) and No Other Section of the Proposed Rule
    i. Research Conducted in Established or Commonly Accepted 
Educational Settings (NPRM at Sec.  __.104(d)(1); current Rule at 
Sec.  __.101(b)(1))
    (1) NPRM Goal
    (2) Current Rule
    (3) NPRM Proposal
    (4) Questions for Public Comment
    ii. Research and Demonstration Projects Conducted or Supported 
by a Federal Department or Agency (NPRM at Sec.  __.104(d)(2); 
Current Rule at Sec.  __.101(b)(5))
    (1) NPRM Goal
    (2) Current Rule
    (3) ANPRM Discussion
    (4) NPRM Proposal
    (5) Questions for Public Comment
    iii. Research Involving Benign Interventions in Conjunction With 
the Collection of Data fFrom an Adult Subject (NPRM at Sec.  
__.104(d)(3))
    (1) NPRM Goal
    (2) Current Rule
    (3) ANPRM Discussion
    (4) NPRM Proposal
    (5) Questions for Public Comment
    iv. Taste and Food Quality Evaluation and Consumer Acceptance 
Studies (NPRM at Sec.  __.104(d)(4); Current Rule at Sec.  
__.101(b)(6))
    (1) Question for Public Comment
    c. Exemptions Subject to the Documentation Requirements of Sec.  
__.104(c) and the Privacy Safeguards Described in Sec.  __.105
    i. Questions for Public Comment
    ii. Research Involving Educational Tests, Surveys, Interviews, 
or Observation of Public Behavior if the Information Is Recorded 
With Identifiers and Even if the Information Is Sensitive (NPRM at 
Sec.  __.104(e)(1))
    (1) NPRM Goals
    (2) Current Rule
    (3) ANPRM Discussion
    (4) NPRM Proposal
    (5). Questions for Public Comment
    iii. Secondary Research Use of Identifiable Private Information 
(NPRM at Sec.  __.104(e)(2))
    (1) NPRM Goal
    (2) Current Rule
    (3) ANPRM Discussion
    (4) NPRM Proposal
    (5) Questions for Public Comment
    d. Exemptions Subject to the Documentation Requirements of Sec.  
__.104(c), the Privacy Safeguards Described in Sec.  __.105, Limited 
IRB Review as Described in Sec.  __.111(a)(9), and Broad Consent in 
Accordance With Sec.  __.116(c)
    i. NPRM Goals
    ii. Current Rule
    iii. ANPRM Discussion
    iv. NPRM Proposals
    (1) Exemption for the Storage or Maintenance of Biospecimens or 
Identifiable Private Information for Secondary Research Use (NPRM at 
Sec.  __.104(f)(1))
    (2) Exemption for Secondary Research Use of Biospecimens or 
Identifiable Private Information Where Broad Consent Has Been Sought 
and Obtained (NPRM at Sec.  __.104(f)(2))
    v. Questions for Public Comment
    e. Applicability of Exemptions to the Subparts (NPRM at Sec.  
__.104(b); Current Rule at Footnote 1)
    i. Current Rule
    ii. NPRM Proposals
    ii. Questions for Public Comment
    f. What would change in the exemptions?
    B. Proposed Changes To Obtaining, Waiving, and Documenting 
Informed Consent (Sec. Sec.  __.116 and__.117)
    1. Required Elements of Informed Consent (NPRM at Sec.  
__.116(a), (b))
    a. NPRM Goal
    b. Current Rule
    c. ANPRM Discussion
    d. NPRM Proposals
    e. What would change?
    f. Question for Public Comment
    2. Broad Consent to the Storage, Maintenance and Secondary 
Research Use of Biospecimens and Identifiable Private Information 
(NPRM at Sec.  __.116(c), (d))
    a. NPRM Goal
    b. Current Rule
    c. ANPRM Discussion
    d. NPRM Proposal
    e. What would change?
    f. Questions for Public Comment
    3. Waiver of Informed Consent or Documentation of Informed 
Consent (NPRM at Sec. Sec.  __.116(e), (f) and __.117)
    a. NPRM Goals
    b. Current Rule
    c. ANPRM Discussion
    d. NPRM Proposals
    e. What would change?
    f. Questions for Public Comment
    4. Posting of Consent Forms
    a. NPRM Goals
    b. NPRM Proposal
    c. What would change?
    C. Proposed Changes To Protect Information and Biospecimens 
(NPRM at Sec.  __.105)
    1. NPRM Goal
    2. Current Rule and Other Regulatory or Statutory Requirements
    3. ANPRM Discussion
    4. NPRM Proposals
    5. What would change?
    6. Questions for Public Comment
    D. Harmonization of Agency Guidance (NPRM at Sec.  __.101(j))
    1. NPRM Goal
    2. Current Rule
    3. ANPRM Discussion
    4. NPRM Proposal
    5. What would change?
    6. Question for Public Comment
    E. Cooperative Research (NPRM and Current Rule at Sec.  __.114) 
and Proposal To Cover Unaffiliated IRBs Not Operated by an 
Institution Holding a Federalwide Assurance (NPRM at Sec.  
__.101(a))
    1. NPRM Goal
    2. Current Rule
    3. Relevant Prior Proposals and Discussions
    4. NPRM Proposals
    5. What would change?
    6. Questions for Public Comment
    F. Changes To Promote Effectiveness and Efficiency in IRB 
Operations
    1. Continuing Review of Research (NPRM at Sec.  __.109(f); 
Current Rule at Sec.  __.109(e))
    a. NPRM Goal
    b. Current Rule
    c. ANPRM Discussion
    d. NPRM Proposals
    e. What would change?
    2. Expedited Review Procedures and the Definition of ``Minimal 
Risk'' (NPRM at Sec. Sec.  __.110 and __.102(j))
    a. NPRM Goal
    b. Current Rule
    c. ANPRM Discussion
    d. NPRM Proposal
    e. What would change?
    f. Questions for Public Comment
    G. Proposed Changes to IRB Operational Requirements
    1. Proposed Criteria for IRB Approval of Research (NPRM at Sec.  
__.111)
    a. NPRM Goals
    b. Current Rule
    c. ANPRM Discussion
    d. NPRM Proposals
    e. What would change?
    f. Questions for Public Comment
    2. Proposed Revisions To IRB Operations, Functions, and 
Membership Requirements
    a. NPRM Goal
    b. Current Rule
    c. NPRM Proposal
    d. What would change?
    e. Question for Public Comment
    H. Other Proposed Changes
    1. Proposal To Extend the Common Rule to All Clinical Trials 
(With Exceptions) (NPRM at Sec.  __.101(a)(1))
    a. NPRM Goals

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    b. Current Rule
    c. ANPRM Discussion
    d. NPRM Proposal
    e. What Would Change?
    f. Questions for Public Comment
    2. Changes to the Assurance Process (NPRM at Sec. Sec.  __.103 
and __.108; Current Rule at Sec.  __.103)
    a. NPRM Goal
    b. Current Rule
    c. NPRM Proposals
    d. What would change?
    e. Question for Public Comment
    3. Department or Agency Discretion About Applicability of the 
Policy (NPRM at Sec.  __.101(c), (d), (i)) and Discretion Regarding 
Additional Requirements Imposed by the Conducting or Supporting 
Department or Agency (NPRM and Current Rule at Sec.  __.124)
    a. NPRM Goals
    b. Current Rule
    c. NPRM Proposals
    4. Research Covered by This Policy Conducted in Foreign 
Countries (NPRM at Sec.  __.101(h))
    I. Effective and Compliance Dates of New Rule (NPRM at Sec.  
__.101(k))
    1. Effective Dates
    2. Transition Provisions
    a. Research Initiated Prior to the Effective Date of This 
Subpart (NPRM at Sec.  __.101(k)(1))
    b. Use of Prior Collections of Biospecimens (NPRM at Sec.  
__.101(k)(2))
III. Regulatory Impact Analyses
IV. Environmental Impact
V. Paperwork Reduction Act
VI. Summary of Comments Received on the 2011 Common Rule ANPRM
VII. Regulatory Text

Executive Summary

Purpose of the Regulatory Action

    Individuals who are the subjects of research may be asked to 
contribute their time and assume risk to advance the research 
enterprise, which benefits society at large. U.S. federal regulations 
governing the protection of human subjects in research have been in 
existence for more than three decades. The Department of Health, 
Education, and Welfare (HEW) first published regulations for the 
protection of human subjects in 1974, and the Department of Health and 
Human Services (HHS) revised them in the early 1980s. During the 1980s, 
HHS began a process that eventually led to the adoption of a revised 
version of the regulations by 15 U.S. federal departments and agencies 
in 1991. The purpose of this effort was to promote uniformity, 
understanding, and compliance with human subject protections as well as 
to create a uniform body of regulations across Federal departments and 
agencies (subpart A of 45 CFR part 46), often referred to as the 
``Common Rule'' for the Protection of Human Subjects.
    Since the Common Rule was promulgated, the volume and landscape of 
research involving human subjects have changed considerably. Research 
with human subjects has grown in scale and become more diverse. 
Examples of developments include: An expansion in the number and type 
of clinical trials, as well as observational studies and cohort 
studies; a diversification of the types of social and behavioral 
research being used in human subjects research; increased use of 
sophisticated analytic techniques for use with human biospecimens; and 
the growing use of electronic health data and other digital records to 
enable very large data sets to be analyzed and combined in novel ways. 
Yet these developments have not been accompanied by major change in the 
human subjects research oversight system, which has remained largely 
unchanged over the last two decades.
    The regulations are codified in each department or agency's title 
or chapter of the Code of Federal Regulations (CFR). The Common Rule 
was based on HHS' regulations, 45 CFR part 46, subpart A, and includes 
identical language in the separate regulations of each department and 
agency.
    Although they have not issued the Common Rule in regulations, three 
departments and agencies currently comply with all subparts of the HHS 
protection of human subjects regulations at 45 CFR part 46. These are 
the Central Intelligence Agency (CIA), the Department of Homeland 
Security (DHS), and the Social Security Administration (SSA). DHS, and 
SSA are joining this proposed rulemaking with the intent of codifying 
the final rule in their own agency regulations.
    Pursuant to Executive Order 12333 of December 4, 1981, as amended, 
elements of the Intelligence Community must comply with the guidelines 
issued by the Department of Health and Human Services regarding 
research on human subjects found in 45 CFR part 46. This proposed 
rulemaking does not supersede the Executive Order. The Office of the 
Director of National Intelligence and the CIA will continue to adhere 
to the HHS guidelines, pursuant to the Executive Order, when the final 
rule is implemented.
    DHS, created after issuance of the Common Rule, is required by 
statute (Pub. L. 108-458, title VIII, section 8306) to comply with 45 
CFR part 46, or with equivalent regulations promulgated by the 
Secretary of Homeland Security or his designee. This proposed 
rulemaking initiates the process of promulgating equivalent 
regulations, consistent with statute. Once DHS executes a final rule, 
DHS will comply with the DHS regulations as the requirements will be 
equivalent to compliance with HHS regulations at 45 CFR part 46, 
subpart A.
    SSA was separated from HHS in 1995 and, pursuant to the transition 
rules provided in Section 106 of title 1 of Public Law 103-296, must 
apply all regulations that applied to SSA before the separation, absent 
action by the Commissioner. Once the final rule is codified in SSA 
regulations, SSA will follow the SSA regulations instead of HHS 
regulations at 45 CFR part 46, subpart A. See Public Law 103-296 Sec.  
106(b), 108 Stat. 1464, 1476.
    Another department is joining this proposed rulemaking. The 
Department of Labor (DOL) is not a signatory to the current Common 
Rule, and is joining this proposed rulemaking in order to promulgate 
the Common Rule in DOL regulations and to apply the regulations to 
human subjects research that DOL may conduct or support, pending the 
scope of the final rule.
    Finally, note that there are two current Common Rule agencies that 
are not listed as part of this proposed rulemaking. The Department of 
Housing and Urban Development (HUD) supports this proposal, but due to 
certain statutory prepublication requirements governing HUD rules, HUD 
will adopt this proposal through a separate rulemaking. The Consumer 
Product Safety Commission (CPSC), subject to Commission vote, also 
intends to adopt this proposed rule through a separate rulemaking.
    On July 26, 2011, the Office of the Secretary of HHS, in 
coordination with the Executive Office of the President's Office of 
Science and Technology Policy (OSTP), published an advanced notice of 
public rulemaking (ANPRM) to request comment on how current regulations 
for protecting human subjects who participate in research might be 
modernized and revised to be more effective.\1\ The ANPRM sought 
comment on how to better protect human subjects who are involved in 
research while facilitating valuable research and reducing burden, 
delay, and ambiguity for investigators.
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    \1\ 76 FR 44512 (Jul. 26, 2011).
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    Since the publication of the ANPRM, science has continued to 
advance, as has the dialogue regarding the changing nature of research 
and the preferred balance of protections for research participants 
among the principles of respect for persons, beneficence, and justice. 
Important elements of that debate have centered on the appropriate 
level of transparency in government and medicine and how patient and 
research participant expectations should be incorporated into 
government policies.

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These factors have helped shape the development of the regulatory 
actions proposed in this NPRM.
    The proposal also benefits from public comments submitted in 
response to more recent policy proposals regarding specific topics such 
as informed consent through the Office for Human Research Protection 
(OHRP)'s Draft Guidance on Disclosing Reasonably Foreseeable Risks in 
Research Evaluating Standards of Care \2\ and the use of a single 
institutional review board (IRB) for multi-site research studies 
through the National Institutes of Health (NIH)'s Draft Policy on the 
Use of a Single Institutional Review Board for Multi-Site Research.\3\
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    \2\ 79 FR 63630 (Oct. 24, 2014).
    \3\ National Institutes of Health. (2014, December 14). Request 
for Comments on the Draft NIH Policy on the Use of a Single 
Institutional Review Board for Multi-Site Research. See more at: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-026.html#sthash.fmjlNRi6.dpuf. Retrieved from National Institutes of 
Health, Office of Extramural Research: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-026.html.
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    Finally, the NPRM more thoroughly addresses behavioral and social 
science research perspectives and the broader types of research 
conducted or otherwise supported by the other Common Rule agencies. 
Similarly, the proposal benefits from continuing efforts at HHS to 
harmonize human subjects policies, particularly between OHRP and the 
U.S. Food and Drug Administration (FDA).

Summary of the Major Provisions of the Proposed Regulatory Action

    The goals of the NPRM are to increase human subjects' ability and 
opportunity to make informed decisions; reduce potential for harm and 
increase justice by increasing the uniformity of human subject 
protections in areas such as information disclosure risk, coverage of 
clinical trials, and coverage of IRBs; and facilitate current and 
evolving types of research that offer promising approaches to treating 
and preventing medical and societal problems through reduced ambiguity 
in interpretation of the regulations, increased efficiencies in the 
performance of the review system, and reduced burdens on researchers 
that do not appear to provide commensurate protections to human 
subjects. It is hoped that these changes will also build public trust 
in the research system.
    An example of some major changes being proposed that will better 
protect research subjects and help build public trust are the rules 
relating to informed consent. With regard to informed consent in 
general (such as consent to participating in clinical trials), the 
rules would be significantly tightened to make sure that the process 
becomes more meaningful. Consent forms would no longer be able to be 
unduly long documents, with the most important information often buried 
and hard to find. They would need to give appropriate details about the 
research that is most relevant to a person's decision to participate in 
the study, such as information a reasonable person would want to know, 
and present that information in a way that highlights the key 
information. In addition, to assure that these rules do indeed change 
current practices, there will be a one-time posting requirement for the 
consent forms for clinical trials, so that anyone drafting a consent 
form will do so knowing that it will eventually be subject to public 
scrutiny.
    In addition, informed consent would generally be required for 
secondary research with a biospecimen (for example, part of a blood 
sample that is left over after being drawn for clinical purposes), even 
if the investigator is not being given information that would enable 
him or her to identify whose biospecimen it is. Such consent would not 
need to be obtained for each specific research use of the biospecimen, 
but rather could be obtained using a ``broad'' consent form in which a 
person would give consent to future unspecified research uses.
    The NPRM also attempts to strengthen the effectiveness and 
efficiency of the oversight system by making the level of review more 
proportional to the seriousness of the harm or danger to be avoided. 
Research that poses greater risk to subjects should receive more 
oversight and deliberation than less risky research. The NPRM seeks to 
avoid requirements that do not enhance protection and impose burden, 
which can decrease efficiency, waste resources, erode trust, and 
obscure the true ethical challenges that require careful deliberation 
and stakeholder input. Cumbersome and outdated regulatory standards 
overwhelm and distract institutions, IRBs, and investigators in ways 
that stymie efforts to appropriately address the real risks and 
benefits of research.
    The result of these types of changes, as the NPRM proposes to 
implement them, is that some studies that currently require IRB review 
would now become exempt. Some that are currently exempt would 
specifically be declared as outside the scope of the regulations 
(``excluded''), and thus would not require any administrative or IRB 
review. Further, in terms of determining when a study is exempt, a web-
based ``decision tool'' will be created. That decision tool will 
provide a determination of whether or not a study is exempt. That 
result, so long as the tool was provided with accurate information, 
will be presumed by the Common Rule agencies to be an appropriate 
determination of exempt status. Thus, it is expected that in many 
instances the tool would be used by the investigators themselves, thus 
obviating both the need for further review and the concern that the 
institution might be subjecting itself to future liability by allowing 
investigators to use the tool. For all of the excluded and exempt 
research activities, this NPRM also affirms the importance of applying 
the ethical principle of respect for persons, in addition to the 
importance of abiding by this principle in fully regulated non-exempt 
research involving human subjects.
    The following list encompasses the most significant changes to the 
Common Rule proposed in the NPRM:
    (1) Improve informed consent by increasing transparency and by 
imposing stricter new requirements regarding the information that must 
be given to prospective subjects, and the manner in which it is given 
to them, to better assure that subjects are appropriately informed 
before they decide to enroll in a research study.
    (2) Generally require informed consent for the use of stored 
biospecimens in secondary research (for example, part of a blood sample 
that is left over after being drawn for clinical purposes), even if the 
investigator is not being given information that would enable him or 
her to identify whose biospecimen it is. That consent would generally 
be obtained by means of broad consent (i.e., consent for future, 
unspecified research studies) to the storage and eventual research use 
of biospecimens.
    (3) Exclude from coverage under the Common Rule certain categories 
of activities that should be deemed not to be research, are inherently 
low risk, or where protections similar to those usually provided by IRB 
review are separately mandated.
    (4) Add additional categories of exempt research to accommodate 
changes in the scientific landscape and to better calibrate the level 
of review to the level of risk involved in the research. A new process 
would allow studies to be determined to be exempt without requiring any 
administrative or IRB review. Certain exempt and all non-exempt 
research would be required to provide privacy safeguards for 
biospecimens and identifiable private information. New categories 
include:
    a. certain research involving benign interventions with adult 
subjects;

[[Page 53937]]

    b. research involving educational tests, surveys, interviews or 
observations of public behavior when sensitive information may be 
collected, provided that data security and information privacy 
protections policies are followed;
    c. secondary research use of identifiable private information 
originally collected as part of a non-research activity, where notice 
of such possible use was given;
    d. storing or maintaining biospecimens and identifiable private 
information for future, unspecified secondary research studies, or 
conducting such studies, when a broad consent template to be 
promulgated by the Secretary of HHS is used, information and 
biospecimen privacy safeguards are followed, and limited IRB approval 
of the consent process used is obtained.
    (5) Change the conditions and requirements for waiver or alteration 
of consent such that waiver of consent for research involving 
biospecimens (regardless of identifiability) will occur only in very 
rare circumstances.
    (6) Mandate that U.S. institutions engaged in cooperative research 
rely on a single IRB for that portion of the research that takes place 
within the United States, with certain exceptions. To encourage the use 
of IRBs that are otherwise not affiliated with or operated by an 
assurance-holding institution (``unaffiliated IRBs''), this NPRM also 
includes a proposal that would hold such IRBs directly responsible for 
compliance with the Common Rule.
    (7) Eliminate the continuing review requirement for studies that 
undergo expedited review and for studies that have completed study 
interventions and are merely analyzing data or involve only 
observational follow-up in conjunction with standard clinical care.
    (8) Extend the scope of the policy to cover all clinical trials, 
regardless of funding source, conducted at a U.S. institution that 
receives federal funding for non-exempt human subjects research.
    In sum, the proposed modifications described above are designed to 
continue to uphold the ethical principles upon which the Common Rule is 
based, as applied to the current social, cultural, and technological 
environment.
    The legal authority for the departments and agencies that are 
signatories to this action is as follows:
    Department of Homeland Security, 5 U.S.C. 301; Public Law 107-296, 
sec. 102, 306(c); Public Law 108-458, sec. 8306. Department of 
Agriculture, 5 U.S.C. 301. Department of Energy, 5 U.S.C. 301; 42 
U.S.C. 7254. National Aeronautics and Space Administration, 5 U.S.C. 
301. Department of Commerce, 5 U.S.C. 301. Social Security 
Administration, 5 U.S.C. 301; 42 U.S.C. 289(a). Agency for 
International Development, 5 U.S.C. 301. Department of Justice, 5 
U.S.C. 301; 28 U.S.C. 509-510. Department of Labor, 5 U.S.C. 301; 29 
U.S.C. 551. Department of Defense, 5 U.S.C. 301. Department of 
Education, 5 U.S.C. 301; 20 U.S.C. 1221e-3, 3474. Department of 
Veterans Affairs, 5 U.S.C. 301; 38 U.S.C. 501, 7331, 7334. 
Environmental Protection Agency, 5 U.S.C. 301. Department of Health and 
Human Services, 5 U.S.C. 301; 42 U.S.C. 289. National Science 
Foundation, 5 U.S.C. 301. Department of Transportation, 5 U.S.C. 301.

Estimated Costs and Benefits

    Table 1 summarizes the quantified and non-quantified benefits and 
costs of all proposed changes to the Common Rule. Over the 2016-2025 
period, present value benefits of $2,629 million and annualized 
benefits of $308 million are estimated using a 3 percent discount rate; 
present value benefits of $2,047 million and annualized benefits of 
$291 million are estimated using a 7 percent discount rate. Present 
value costs of $13,342 million and annualized costs of $1,564 million 
are estimated using a 3 percent discount rate; present value costs of 
$9,605 million and annualized costs of $1,367 million are estimated 
using a 7 percent discount rate. Non-quantified benefits include 
improved human subjects protections in clinical trials and biospecimen 
research not currently subject to oversight; enhanced oversight of 
research reviewed by unaffiliated IRBs; increased uniformity in 
regulatory requirements among Common Rule agencies; standardization of 
human subjects protections when variation among review IRBs is not 
warranted; revised informed consent forms and processes; improved 
protection of biospecimens and individually identifiable private 
information; and increased transparency of Common Rule agency-supported 
clinical trials to inform the development of new consent forms. Non-
quantified costs include the time needed for consultation among Common 
Rule agencies before federal guidance is issued; and the time needed by 
investigators to obtain, document, and track the permissible uses of 
biospecimens and identifiable private information for secondary 
research use.

                     Table 1--Accounting Table of Benefits and Costs of All Proposed Changes
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits.....................            2,629             2,047               308               291
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Improved human subjects protections in clinical trials and biospecimen research not currently subject to
     oversight; enhanced oversight in research reviewed by unaffiliated IRBs; increased uniformity in regulatory
     requirements among Common Rule agencies; ethical benefit of respecting an individual's wishes in how his or
     her biospecimens are used in future research; standardization of human subjects protections when variation
     among review IRBs is not warranted; improved informed consent forms and processes; improved protection of
     biospecimens and individually identifiable private information; better ensuring availability of
     biospecimens for future research activities; and increased transparency of Common Rule-supported clinical
     trials to inform the development of new consent forms......................................................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs                                   13,342             9,605             1,564             1,367
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    Time for consultation among Common Rule agencies before federal guidance is issued; time for investigators
     to obtain consent for secondary use of biospecimens or identifiable private information....................
----------------------------------------------------------------------------------------------------------------


[[Page 53938]]

I. The Rationale for Modernizing the Common Rule

A. The Changing Nature of Research

    In the last two decades there has been a paradigm shift in how 
research is conducted. Evolving technologies, including imaging, mobile 
technologies, and the growth in computing power have changed the scale 
of information collected in many disciplines. Computer scientists, 
engineers, and social scientists are developing techniques to integrate 
different types of data so they can be combined, mined, analyzed, and 
shared. Research has also increased, evolved, and diversified in other 
areas, such as national security, crime and crime prevention, 
economics, education, and the environment, using a wide array of 
methodologies in the social sciences and multidisciplinary fields. The 
advent of sophisticated computer software programs, the internet, and 
mobile technology has created new areas of research activity, 
particularly within the social and behavioral sciences. In biomedical 
science, the Human Genome Project laid the foundation for precision 
medicine and promoted an environment of data sharing and innovation in 
analytics and technology, and drew attention to the need for policies 
that support a changing research landscape. New technologies, including 
genomic sequencing, have quickly led to exponential growth in the data 
to which investigators have access. The sheer volume of data that can 
be generated in research, the ease with which it can be shared, and the 
ways in which it can be used to identify individuals were simply not 
possible, or even imaginable, when the Common Rule was first adopted.
    Research settings are also shifting. While much biomedical research 
continues to be conducted in academic medical centers, more research is 
being conducted in clinical care settings, thus combining research and 
medical data. Biospecimen repositories and large databases have made it 
easier to do research on existing biospecimens and data. Clinical 
research networks connected through electronic health records (EHRs) 
have developed methods for extracting clinical data for research 
purposes and are working toward integration of research data into EHRs 
in a meaningful way. The overall volume of research has increased 
across the board, with growing reliance on research networks and multi-
site studies. Large cohort studies number well into the hundreds in the 
United States alone and many collect biospecimens and data on the same 
people over many years. Recent trends clearly show that the scientific 
community recognizes the value of data sharing and open-source 
resources and understands that pooling intellectual resources and 
capitalizing on efficient uses of data and technology represent the 
best ways to advance knowledge.
    At the same time, the level of public engagement in the research 
enterprise has changed; more people want to play an active role in 
research, particularly related to health, and they have different 
expectations than when the Common Rule was first established. A more 
participatory research model is emerging in social, behavioral, and 
biomedical research, one in which potential research subjects and 
communities express their views about the value and acceptability of 
research studies. This participatory model has emerged alongside a 
broader trend in American society, facilitated by the widespread use of 
social media, in which Americans are increasingly sharing identifiable 
personal information and expect to be involved in decisions about how 
to further share the personal information, including health-related 
information that they have voluntarily chosen to provide. In many ways, 
these changes are extensions of the fact that over the past half-
century, rather than being passive recipients of health advice and 
treatment, patients have gradually become more active in decisions 
about their health and health care. The shift from a paternalistic 
research environment to one where participants are active partners in 
biomedical and behavioral research is a critical development in human 
subjects research.
    As technology evolves, so does the nature of the risks and benefits 
of participating in certain types of research. Many studies do not 
involve interaction with research subjects, but instead involve, for 
example, analyzing information obtained from medical records, 
administrative claims data, education records, criminal justice 
records, research data shared through data repositories, and existing 
biospecimens stored in repositories. Risks related to these types of 
research studies are largely informational, not physical; that is, 
harms could result primarily from the inappropriate release of 
information and not from the research interventions themselves. 
Nonetheless, those harms can be significant.
    New methods, more powerful computers, and easy access to large 
administrative datasets produced by local, state, and federal 
governments have meant that some types of data that formerly were 
treated as non-identified can now be re-identified through combining 
large amounts of information from multiple sources. In 2013, scientists 
demonstrated that the identity of individual research subjects could be 
ascertained by collating and analyzing certain types of genomic data, 
including genomic data from publicly available information sources.\4\ 
Thus, the possibility of fully identifying biospecimens and some types 
of data from which direct identifiers had been stripped or did not 
originally include direct identifiers has grown, requiring vigilance to 
ensure that such research be subject to appropriate oversight. Most 
importantly, people want to be asked for their permission. A growing 
body of survey data show that many prospective participants want to be 
asked for their consent before their biospecimens are used in 
research.5 6 7 8
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    \4\ Gymrek M et al. ``Identifying personal genomes by surname 
inference''. Science 339.6117(2013) 0: 321-324.
    \5\ Kaufman DJ et al. Public opinion about the importance of 
privacy in biobank research. American Journal of Human Genetics 2009 
Nov;85(5):643-654.
    \6\ Vermeulen E et al. A trial of consent procedures for future 
research with clinically derived biological samples. British Journal 
of Cancer 2009 Nov 3;101(9):1505-1512.
    \7\ Trinidad SB et al. Research practice and participant 
preferences: The growing gulf. Science 2011 Jan 21; 331(6015):287-
288.
    \8\ Simon CM et al. Active choice but not too active: Public 
perspectives on biobank consent models. Genetics in Medicine. 2011 
Sep;13(9):821-831.
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    Because of these shifts in science, technology, and public 
engagement expectations, a wide range of stakeholders have raised 
concerns about the limitations of the existing framework, arguing for a 
re-evaluation of how the fundamental principles that underlie the 
Common Rule --respect for persons, beneficence, and justice--are 
applied in practice to the myriad new contexts in which U.S. research 
is conducted in the 21st century.9 10 Dialogue focuses 
around whether the current system:
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    \9\ Emanuel EJ, Wood A, Fleischman A, et al. Oversight of human 
participants research: Identifying problems to evaluate reform 
proposals. Annals of Internal Medicine 2004;141(4):282-291.
    \10\ Maschke K. Human research protections: Time for regulatory 
reform? Hastings Center Report. 2008 Mar-Apr; 38(2):19-22.
---------------------------------------------------------------------------

     Is sufficiently supportive of a participant-centered 
research model that adequately respects participants as partners;
     is not sufficiently risk-based, resulting in both over- 
and under-regulation of research activities; 11 12 13
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    \11\ Kim S, Ubel P, De Vries R. Pruning the regulatory tree. 
Nature 2009 Jan 29;457(7229):534-535.
    \12\ Wendler D, Varma S. Minimal risk in pediatric research. 
Journal of Pediatrics. 2006 Dec;149(6):855-861.
    \13\ Infectious Disease Society of America. Grinding to a halt: 
The effects of the increasing regulatory burden on research and 
quality improvement efforts. Clinical Infectious Diseases 2009 Aug 
1;49(3):328-335.

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[[Page 53939]]

     is sufficiently tailored to new and emerging areas of 
research, including social and behavioral research and research 
involving the collection and use of genetic information; 
14 15 16 17 18 19
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    \14\ National Research Council. Protecting Participants and 
Facilitating Social and Behavioral Sciences Research. Washington, 
DC: National Academies Press, 2003.
    \15\ Anderlik M. Commercial biobanks and genetic research: 
Ethical and legal issues. American Journal of Pharmacogenomics 
2003;3(3):203-215.
    \16\ Schrag ZM. How talking became human subjects research: The 
Federal regulation of the social sciences, 1965-1991. Journal of 
Policy History 2009 January; 21(01):3-37.
    \17\ Hansson MG et al. Should donors be allowed to give broad 
consent to future biobank research? Lancet Oncology 2006 Mar; 
7(3):266-269.
    \18\ Murphy J et al. Public perspectives on informed consent for 
biobanking. American Journal of Public Health 2009 December; 
99(12):2128-2134.
    \19\ Kaufman DJ et al. Public opinion about the importance of 
privacy in biobank research. American Journal of Human Genetics 2009 
Nov; 85(5):643-654.
---------------------------------------------------------------------------

     effectively informs subjects of psychological, 
informational, or privacy risks; 20 21 22
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    \20\ Paasche-Orlow MK, Taylor HA, Brancati F. Readability 
standards for informed-consent forms as compared with actual 
readability. New England Journal of Medicine 2003 Feb 20; 
348(8):721-726.
    \21\ Schneider CE. The Hydra. Hastings Center Report 2010 Jul-
Aug; 40(4):9-11.
    \22\ Albala I, Doyle M, Appelbaum PS. The evolution of consent 
forms for research: A quarter century of changes. IRB Ethics & Human 
Research 2010 May-June; 32(3):7-11.
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     adequately accounts for the needs of a ``learning'' 
healthcare system for continual quality improvement; 
23 24 25
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    \23\ Faden RR, Beauchamp TL, Kass NE. Informed consent, 
comparative effectiveness, and learning health care. New England 
Journal of Medicine 2014 Feb 20;370(8):766-768.
    \24\ Dziak K et al. Variations among institutional review board 
reviews in a multisite health services research study. Health 
Services Research 2005 Feb; 40(1):279-290.
    \25\ Lynn J et al. The ethics of using quality improvement 
methods in health care. Annals of Internal Medicine 2007 May 
1;146(9):666-673.
---------------------------------------------------------------------------

     provides sufficient mechanisms to ensure the consistency, 
quality, and accountability of IRB decision-
making.26 27 28 29
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    \26\ Heimer CA et al. Regulating creativity: Research and 
survival in the IRB iron cage. Northwestern University Law Review 
2007; 101:593-641.
    \27\ Green LA et al. Impact of institutional review board 
practice variation on observational health services research. Health 
Services Research 2006 Feb; 41(1):214-230.
    \28\ Jansen LA. Local IRBs, multicenter trials, and the ethics 
of internal amendments. IRB 2005 Jul-Aug;27(4):7-11.
    \29\ Schrag Z. Ethical Imperialism. Baltimore, MD: Johns Hopkins 
University Press, 2010.
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B. Public Comments, Expert Advice, Stakeholder Dialogue

    The revisions to the Common Rule proposed here are based upon a 
variety of sources of public, stakeholder, and expert comments and 
advice. First, the NPRM more thoroughly addresses social science and 
behavioral research perspectives, benefiting from guidance provided by 
a National Research Council's consensus report entitled ``Proposed 
Revisions to the Common Rule for the Protection of Human Subjects in 
the Behavioral and Social Sciences.'' \30\ The Report was commissioned 
to ensure that the issues related to research involving human subjects 
in social and behavioral research would be addressed appropriately, in 
view of what had been said in the ANPRM. The Panel made numerous 
recommendations, including recommendations about what research studies 
should not undergo review, about calibrating the level of IRB review to 
the level of risk, about the desirability of privacy and 
confidentiality protections in social and behavioral research other 
than those of the Health Insurance Portability and Accountability Act 
of 1996 (HIPAA), and about improving informed consent by placing 
greater emphasis on the process of consent. The NPRM revises some of 
the ANPRM proposals in light of those recommendations.
---------------------------------------------------------------------------

    \30\ National Research Council of the National Academies. 
(2014). Proposes Revisions to the Common Rule for the Protections of 
Human Subjects in the Behavioral and Social Science. The National 
Academies Press, 13-168. Retrieved from http://www.nap.edu/catalog/18614/proposed-revisions-to-the-common-rule-for-the-protection-of-human-subjects-in-the-behavioral-and-social-sciences.
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    Second, since the publication of the ANPRM, HHS has continued to 
solicit public comment on a variety of human subjects related issues, 
including consent, the use of a single IRB for multi-site studies, and 
sharing of genomic data. Although these policies were more specific 
than the issues raised in the ANPRM, the responses received from public 
comments provide insight for refining the proposals initially put 
forward in the ANPRM. Of particular interest:
     NIH's proposal that it expects the use of a single IRB for 
all multi-site research studies funded or conducted by the NIH.\31\ 
Under that proposal, all domestic sites of a multi-site study would be 
expected, as a condition of NIH funding, to use a single IRB of record. 
In response to this proposal, NIH received 165 comments from a range of 
stakeholders, including investigators, IRB members, and members of the 
public. The majority of respondents were supportive; however concerns 
were raised that it would be expensive and time-consuming to identify a 
single IRB for each new multi-site study.
---------------------------------------------------------------------------

    \31\ National Institutes of Health. (2014, December 14). Request 
for Comments on the Draft NIH Policy on the Use of a Single 
Institutional Review Board for Multi-Site Research. See more at: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-026.html#sthash.fmjlNRi6.dpuf. Retrieved from National Institutes of 
Health, Office of Extramural Research: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-026.html.
---------------------------------------------------------------------------

     OHRP's draft guidance discussing the required content of 
consent language for research done within the standard of care.\32\ In 
August of 2013, prior to the publication of the draft guidance 
document, HHS held a public meeting to hear from the community on 
issues raised during the debate surrounding the SUPPORT study.\33\ The 
public meeting and the draft guidance document spurred a significant 
public discussion about the nature of the information included in 
informed consent forms, specifically how investigators should 
communicate the risks of research studies done within the standard of 
care. A total of 93 comments were received from bioethicists, 
investigators and research institutions, hospitals and physicians, IRB 
members, patient advocates, and industry.
---------------------------------------------------------------------------

    \32\ 79 FR 63630 (Oct. 24, 2014).
    \33\ 78 FR 48163 (Aug 7, 2013).
---------------------------------------------------------------------------

     To enhance human subject protections and reduce regulatory 
burden, OHRP and FDA have been actively working to harmonize the 
agencies' regulatory requirements and guidance for human subject 
research, and the FDA's draft guidance, ``Use of Electronic Informed 
Consent in Clinical Investigations'' was developed as part of these 
efforts. The draft guidance was issued in conjunction with an OHRP 
Federal Register notice soliciting comment on the whether joint final 
guidance would be useful for the regulated community, and whether FDA's 
draft guidance would be appropriate for all research regulated under 45 
CFR part 46, such as social and behavioral research studies. Comments 
were received largely favoring joint guidance, but with separate 
sections addressing research regulated solely by 45 CFR part 46.
     NIH's proposal to promote sharing of large-scale human 
genomic data generated from studies funded or conducted by NIH.\34\ The 
policy lays out an expectation that investigators generating genomic 
data get consent for future research use of those data. The NIH 
received 107 comments on the policy, including many that addressed

[[Page 53940]]

the concept of broad consent for unspecified future research use.
---------------------------------------------------------------------------

    \34\ 79 FR 51345 (Aug. 28, 2014).
---------------------------------------------------------------------------

    There have also been developments on the legislative front that 
have informed the discussions leading up to this NPRM. In December of 
2014, the Newborn Screening Saves Lives Reauthorization Act of 2014 
(Pub. L. 113-240), was signed into law. The new law makes a number of 
changes relevant to the HHS regulations for protecting research 
subjects, including declaring that research with newborn dried blood 
spots that is federally funded pursuant to the Public Health Service 
Act is to be considered research with human subjects, and the 
provisions allowing IRBs to waive consent will not apply. These changes 
will be effective until updates to the Common Rule are promulgated. In 
addition, in April of 2015, the Medicare Access and CHIP 
Reauthorization Act of 2015 (Pub. L. 114-10) was passed. That law 
requires HHS to issue a clarification or modification of the Common 
Rule with regard to how they apply to activities involving clinical 
data registries.
    Most recently, with the launch of the President's Precision 
Medicine Initiative (PMI),35 36 the Federal Government is 
proposing a new research cohort based on a model that puts participants 
at the center.\37\ To understand participant preferences the White 
House and PMI agencies have been hosting a series of roundtables and 
public workshops about public expectations for how participants want to 
engage in research today. These discussions have included individuals 
from many sectors, including prospective research participants, 
patients and patient advocates, privacy experts, bioethicists, academic 
and industry investigators, data scientists, technology innovators, 
healthcare institutions and providers. The government has heard many 
perspectives, with much alignment around the central tenet that 
participants should be active partners in research, and not merely 
passive subjects of research studies. Many are seeking a research 
environment where they can contribute to the greater good and have 
transparency into the research being conducted using their specimens 
and data. The conversations have focused on promoting the ethical 
principles of respect for persons, beneficence, and justice, as well as 
promoting other protections, such as data security and privacy.
---------------------------------------------------------------------------

    \35\ The White House, Office of the Press Secretary. (2015, 
January 30). Fact Sheets: President Obama's Precision Medicine 
Initiative. Retrieved from The White House: https://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet-president-obama-s-precision-medicine-initiative.
    \36\ Collins FS, Varmus H. A New Initiative on Precision 
Medicine. N Engl J Med 2015 Feb; 372:793-795.
    \37\ See also http://www.scientificamerican.com/article/big-precision-medicine-plan-raises-patient-privacy-concerns/, http://www.nih.gov/precisionmedicine/, and http://www.nih.gov/precisionmedicine/.
---------------------------------------------------------------------------

C. Guiding Principles for Proposed Changes

    In 1979, the Belmont Report \38\ was predicated on three principles 
that were felt to be central to shaping an ethical framework for the 
conduct of research with human subjects. The three ethical principles 
are respect for persons, beneficence, and justice. Interpretation of, 
and balancing among, these three principles played a major role in 
shaping what became the development the federal regulations that have 
become known as the Common Rule. The preamble to the proposal considers 
whether and how the interpretation of these fundamental principles 
might be updated within the context of the current technological, 
social, cultural, and ethical environment. That consideration involves 
explicitly identifying the interplay among the principles. The Common 
Rule provides a framework for how researchers and IRBs weigh the often 
conflicting implications of these three principles.
---------------------------------------------------------------------------

    \38\ National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research. (1979). Belmont Report. 
Washington, DC: U.S. Department of Health & Human Services. 
Available at: http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html.
---------------------------------------------------------------------------

    Beneficence: Individuals who participate in research contribute 
their time and may assume significant risks to advance the research 
enterprise. Their valuable contributions produce knowledge that 
benefits society at large. The Belmont Report describes the principle 
of beneficence as the goal of maximizing possible benefits of research 
and minimizing possible harms. This principle has been interpreted to, 
in part, emphasize the benefit associated with the knowledge that might 
be generated by a research study. Evaluating beneficence requires 
examining the likelihood that knowledge would be generated, and how 
important or useful that knowledge might be to the population. When 
more weight is given to research that has the potential to generate a 
great deal of knowledge, particularly knowledge that could be very 
useful to society (such as how to treat serious diseases that are 
currently untreatable), policies would lean in favor of encouraging and 
facilitating more of that type of research.
    A distinct aspect of the principle of beneficence concerns the 
benefits and risks to the specific persons who would be participating 
in a particular research study. In the example of a randomized clinical 
trial comparing two treatments for a disease, the benefits and risks to 
the subjects in the trial are distinct from the possible benefits to 
society as a whole from learning which of the two treatments is better. 
This aspect of beneficence assumes that there are limits on the risks 
to which people should be subject, even if they are willing to undergo 
those risks.
    Society is in an information age. In all facets of one's life 
information about that person is generated, stored, shared, analyzed, 
and often provides tremendous societal value. People share information 
about themselves with large numbers of people with the click of a 
button, and this trend of rapid and widespread sharing is only likely 
to grow. The increase in concern about unauthorized and inadvertent 
information disclosure, in combination with newer research techniques 
that increase the volume and nature of identifiable data suggest the 
need for the Common Rule to more explicitly address data security and 
privacy protection.
    Of particular interest for this proposal is addressing risks from 
inappropriate disclosure of information generated from biospecimens. 
One way to protect subjects from such risks is to bring under oversight 
research for which risks are greater of subjects being identified and 
information being inappropriately disclosed. Although it may be 
difficult to identify individuals from their non-identified 
biospecimens at present, and most investigators would have no need to 
do so unless they were seeking additional associated phenotypic 
information, certain technologies and methods can be used to generate 
data that are unique to the individual who provides the biospecimen, 
and those data can sometimes be combined with other data sources to 
identify the individual. In the future, technologies will facilitate 
the use and analysis of greater variety and volumes of information, and 
there is a possibility that it will be increasingly difficult, if not 
impossible, to make biospecimens fully non-identified. In fact, a 
number of reports have already demonstrated the ability to re-identify 
individuals from biospecimens or data that lack direct 
identifiers.39 40 As analytic techniques become more 
sophisticated and large

[[Page 53941]]

datasets become more accessible, it will not be possible to guarantee 
that an individual could never be identified from a biospecimen or 
combination or data sources, particularly if whole genome sequencing is 
conducted.
---------------------------------------------------------------------------

    \39\ Rothstein MA. Is deidentification sufficient to protect 
health privacy in research? American Journal of Bioethics Sep 2010; 
10(9): 3-11.
    \40\ El Emam K et al. A systematic review of re-identification 
attacks on health data. PLoS One 2011; 6(12):e28071.
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    Respect for Persons: The Belmont Report describes this concept as 
the notion of treating people as autonomous agents, and allowing them 
to make choices based on their own judgments and opinions. Inherent in 
the principle of autonomy is the concept of transparency--clearly 
providing the information necessary for the research participant to 
make such judgments. Transparency requires a clear articulation of 
risks, potential benefits, and alternatives to participating in a 
research study, as well as the purpose of the research. The principle 
of autonomy encompasses the value ascribed to an individual's right to 
know how one's data is being used and who will have access to it. As 
such autonomy also covers the paired concept of protecting those 
persons who lack the capability to make such decisions. There are a 
variety of different ways of demonstrating respect for persons.
    Obtaining informed consent from human subjects for the collection 
and analysis of information about them is one means of implementation 
of respect for persons in the research context. Informed consent is 
designed to ensure that each individual approached to participate in a 
research study fully understands the risks and potential benefits of 
the study so that they have sufficient information to make an 
individualized calculation as to whether or not the tradeoffs inherent 
in participation are worth it for them to agree to participate. Both 
the potential harms and benefits tend to be greater in the context of a 
clinical trial where subjects are randomized to one or another of two 
possible treatments with significantly different suspected risks than 
in situations where subjects are simply asked to provide, for instance, 
a urine sample.
    Notice, in which individuals are informed about how data will be 
used, but explicit consent is not obtained, is another means of 
facilitating transparency. Notice is sometimes used in the context of 
informing people about how data collected for non-research purposes 
(e.g., when providing information in the context of applying for public 
benefits) might be used for either general or specific research 
purposes. Another method for showing respect for persons with regard to 
using data about them for research could be providing them with a right 
to opt out of such research, by, for example, filing a form stating 
such a wish with the holder of the data.
    Related, implicit consent might be obtained when a research subject 
completes a questionnaire. If they did not wish to provide the 
information, presumably they would not be answering the questions. The 
NPRM contains a number of provisions that are designed to further 
promote respect for participants through increases in both transparency 
and opportunities for consent.
    Justice: The Belmont Report describes this principle as being about 
fairness in terms of who receives the benefits from research and who 
bears its burdens. One of the most direct applications of the principle 
of justice to the Common Rule relates to determining who is studied and 
how subjects are selected. This principle also is relevant to 
protection of vulnerable populations. In addition, the idea of justice 
is relevant to one of core goals of this NPRM: Clarifying important 
aspects of the Common Rule where there has been ambiguity in 
interpretation. To the extent that IRBs and others interpret the 
regulations in significantly different ways, the result is that 
participants in research can end up being treated in very different 
ways, even when they are participating in the same study. Thus this 
idea is embedded in all of the NPRM's attempts to make sure that these 
rules are applied in a more uniform and consistent manner.
    The three ethical principles of the Belmont Report often cannot all 
be fulfilled at the same time. In many cases, it will be necessary to 
choose which of those principles will deserve the greatest adherence. 
This NPRM, at its heart, represents an attempt to evaluate the weights 
to be applied to each of these three core principles in a variety of 
specific contexts. Giving greater weight to one of the principles will 
frequently mean a decreased ability to fulfill one of the other 
principles. By necessity, value judgments, influenced by the social 
norms of the time, drive the implementation of the broad principles 
underlying the Belmont Report. The efficacy of the oversight system 
also requires proportionality in weighing the application of these 
three principles. This is reflected in the analysis that follows, in 
terms of evaluating the specific aspects of beneficence, respect for 
persons, and justice that relate to a particular issue, and weighing 
those aspects against one another. Research that poses greater risk 
should receive more attention and deliberation than less risky 
research, and the degree and type of oversight should be commensurate 
with the level of risk. In addition, requirements that do not enhance 
protection but that impose burden can increase inefficiency, waste 
resources, erode trust, and obscure the ethical challenges that require 
careful deliberation and stakeholder input. Cumbersome and outdated 
regulatory standards overwhelm and distract oversight bodies and other 
stakeholders from appropriately addressing the real risks and benefits 
of research.
    There is tremendous support for research in this country. American 
society values advances in knowledge and has reaped the reward of many 
key insights that have led to increases in quality of life and a 
doubling of our life expectancy in the last century. There would not 
have been such strides in medical and behavioral research without the 
willingness of individuals to join research studies. Participants are 
told that they are not likely to benefit directly from any given study, 
yet they choose to participate for the greater good. Beneficence is a 
powerful driver. On the other hand, members of the public deserve, and 
indeed now expect, to know how publicly-funded research is being 
conducted and overseen, and need to have confidence that the interests 
of research participants are adequately protected. Transparency is key 
for developing trust, especially between investigators, funders, 
regulators, and the public.
    Our reassessment of these ethical principles in the context of 
current technology and social norms suggests the need for changes to 
the Common Rule that: (1) Increase subject autonomy by increasing human 
subjects' ability and opportunity to make informed decisions; (2) 
reduce potential for harm and increase justice by increasing the 
uniformity of human subject protections in areas such as information 
disclosure risk, coverage of clinical trials, and coverage of IRBs; and 
(3) increase beneficence by facilitating current and evolving types of 
research that offer promising approaches to treating and preventing 
medical and societal problems though reduced ambiguity in 
interpretation of the regulations, increased efficiencies in the 
performance of the review system, and reduced burdens on researchers 
that do not appear to provide commensurate protections to human 
subjects. If a reasonable balance is struck between protecting human 
research subjects, minimizing the administrative burden of the system, 
and engendering public trust, this should maximize beneficence and 
raise all ships.
    Public comment is sought not only on the provisions outlined below, 
but on whether the proposals strike a reasonable balance among the core

[[Page 53942]]

ethical principles. A better balance among the core principles should 
increase the strength of the partnership between the research 
enterprise and the public, and even greater scientific understanding 
and innovation will be fostered.
    Finally, it is important to note that, to the extent appropriate, 
the intent is to eventually amend the other subparts of the HHS human 
subjects protection regulations in 45 CFR part 46 (subparts B, C, D, 
and E), and consider the need for updates to FDA regulations and other 
relevant Federal departmental or agency regulations with overlapping 
scope.
1. Question for Public Comment
    1. Public comment is sought on whether the proposed changes will 
achieve the objectives of (i) decreasing administrative burden, delay 
and ambiguity for investigators, institutions, and IRBs, and (ii) 
strengthening, modernizing, and making the regulations more effective 
in protecting research subjects.

D. Organization of the NPRM

    Section II of the NPRM, which immediately follows, describes in 
detail the major proposals for revisions to the Common Rule. In 
general, the changes that are likely to be of greatest significance are 
discussed in the earlier parts of section II of this preamble. Section 
II.A is devoted to changes that affect which activities are subject to 
the Common Rule. Following that section are discussions devoted to 
changes relating to informed consent (section II.B), changes relating 
to privacy safeguards for the research use of information and 
biospecimens (section II.C), and a proposal to encourage greater 
harmonization of guidance across the agencies that adhere to the Common 
Rule (section II.D). Discussions of changes relating to how IRBs 
operate, including a proposal to reduce the number of reviews by 
different IRBs that take place for multi-site studies, are in the 
several sections that follow (sections II.E, F and G). The final 
section (section II.H) collects a variety of other changes, including 
expanding the scope of the rule to cover clinical trials that are not 
federally funded but are conducted at institutions that received some 
federal funding for research with human subjects.
    The three sections that follow then discuss various administrative 
review requirements: Regulatory Impact Analyses (section III), 
Environmental Impact (section IV), and Paperwork Reduction Act (section 
V). The final section of the document (section VII) provides the full 
regulatory text of the proposed changes to the Common Rule. Section VI 
provides a comprehensive summary of responses received to the 2011 
Common Rule ANPRM.

II. Major Proposals To Modernize the Common Rule

A. Proposed Changes to the Scope and Applicability of the Regulations

1. Expanding the Definition of Human Subject to Cover Research with 
Non-identified Biospecimens (NPRM at Sec. Sec.  __.102(e) and 
__.101(b)(3)(i))
    This section focuses on the ethical principles associated with the 
secondary research use of biospecimens. These biospecimens may have 
been originally collected from either research or non-research settings 
(e.g., leftover portion of tissue from a clinical biopsy).
a. NPRM Goals
    One of the goals of this NPRM is facilitating cutting edge research 
in genomics and other `omics' such as the transcriptome and the 
microbiome, which generate a wealth of data from biospecimens designed 
to inform the development of treatments and preventative measures for 
chronic diseases such as cancer. Facilitating such research, however, 
requires navigating complex ethical issues. The key question is, under 
what circumstances should the Common Rule govern what research 
investigators are able to do with biospecimens that have been collected 
for some other (e.g., clinical) purpose? (Note that if a researcher 
interacted with an individual to actually collect a biospecimen for 
research purposes--for example, obtaining a saliva sample--that 
``primary'' research activity is already covered under the current 
regulations, and is not the focus of the change discussed in this 
section.) In this case, maximizing the societal value of research would 
mean reducing barriers to the secondary use of biospecimens to the 
extent possible.
    However, there is a growing recognition that many people want to 
have some degree of control over the circumstances in which an 
investigator can derive information about them, above and apart from 
their interest in whether or not that information might be 
inappropriately disclosed. More specifically, a growing body of 
literature shows that in general people prefer to have the opportunity 
to consent (or refuse to consent) to research involving their own 
biological materials.\41\ Furthermore, in 2012, the Presidential 
Commission for the Study of Bioethical Issues highlighted the ethical 
importance of obtaining consent for genomics research and recommended 
that ``unauthorized whole genome sequencing without the consent of the 
individual from whom the sample came'' be prohibited.\42\ Their 
rationale for reaching this conclusion was based on concerns relating 
to privacy as well as autonomy.
---------------------------------------------------------------------------

    \41\ See supra notes 5-8.
    \42\ Presidential Commission for the Study of Bioethical Issues. 
(2012). Privacy and Progress in Whole Genome Sequencing. Washington, 
DC: Presidential Commission for the Study of Bioethical Issues. 
Retrieved from http://bioethics.gov/sites/default/files/PrivacyProgress508_1.pdf.
---------------------------------------------------------------------------

    In assigning weights to the principles of beneficence and respect 
for persons in the context of research with biospecimens, strong 
consideration was given to the fact that failure to acknowledge and 
give appropriate weight to this distinct autonomy interest in research 
using biospecimens could, in the end, diminish public support for such 
research, and ultimately jeopardize our ability to be able to conduct 
the appropriate amount of future research with biospecimens. To that 
end, the proposals given below are designed to meet the goals of 
increasing transparency in when and how biospecimens collected in a 
variety of circumstances will be used for research purposes and 
increasing opportunities for consent. Various ways in which these goals 
might be achieved are the subject of alternative proposals discussed 
below.
b. Current Rule
    The application of the current regulations to secondary research 
use of a biospecimen is tied to the identifiability of the biospecimen 
in the hands of the researcher. In particular, the definition of human 
subject in the current Common Rule at Sec.  __.102(f) states that a 
human subject is a living individual about whom an investigator 
(whether professional or student) conducting research obtains data 
through intervention or interaction with the individual, or 
identifiable private information. Private information is described as 
information that is individually identifiable (i.e., the identity of 
the subject is or may readily be ascertained by the investigator or 
associated with the information) in order for obtaining the information 
to constitute research involving human subjects.
    Consistent with historical interpretation of identifiable private 
information under the Common Rule, the terms ``non-identified'' or 
``non-identifiable'' are used throughout this

[[Page 53943]]

NPRM to signify biospecimens or data that have been stripped of 
identifiers such that an investigator cannot readily ascertain a human 
subject's identity. Re-identification of non-identified or non-
identifiable biospecimens or information may be possible, depending on 
the circumstances. The term ``de-identified'' is distinct; it is only 
used in this proposal to refer specifically to the HIPAA standard of 
non-identifiability.
    Thus, where there is no intervention or interaction with an 
individual, central to determining whether human subjects are involved 
in a research activity covered by the current Common Rule is 
determining the meaning of ``identifiable.'' Under the current Rule, 
provided the biospecimens and data were collected for purposes other 
than the currently proposed research, it is permissible for 
investigators to conduct research on biospecimens and data that have 
been stripped of all identifiers without obtaining consent because the 
non-identified biospecimens and data do not meet the regulatory 
definition of human subject.
    It is, however, worth noting that although informed consent is not 
strictly required by the current regulations when research takes place 
using non-identified biospecimens, some IRBs have indicated that they 
are requiring that investigators explicitly obtain consent for future 
analysis of biospecimens collected in the research setting, and some 
are refusing to waive consent for use of biospecimens collected in non-
research contexts.
c. ANPRM Discussion
    The ANPRM asked whether consent should be required before an 
investigator could conduct research on a non-identified biospecimen. It 
further asked, if consent were to be required, could such consent be 
obtained by having a person provide consent for unspecified future 
research with the biospecimen, instead of requiring that specific 
consent be obtained each time that the biospecimen would actually be 
used in a research study.
    Although HHS does not consider whole genome analysis to produce 
identifiable private information unless additional information is 
available to the investigator that would enable the investigator to 
``readily ascertain'' the identity of the individual, it is 
acknowledged that a time when investigators will be able readily 
ascertain the identity of individuals from their genetic information 
may not be far away. The ANPRM suggested that, regardless of what 
information is removed, it is theoretically possible to extract DNA 
from a biospecimen itself and potentially link it to otherwise 
available data to identify individuals. In addition, irrespective of 
whether biospecimens are considered individually identifiable, the 
ANPRM sought comment on whether the regulations should be changed to 
allow human subjects to decide whether their biospecimens would be 
available for research.
    The ANPRM asked whether some types of genomic data should be 
considered identifiable and, if so, which types (e.g., genome-wide 
single nucleotide polymorphism [SNP] analyses or whole genome 
sequences). It also asked whether a human biospecimen should be 
considered inherently identifiable.
    The ANPRM also suggested that the definition of identifiability in 
the Common Rule be modified to better harmonize it with other 
regulatory definitions of identifiability within HHS. The ANPRM 
considered adopting the HIPAA Privacy Rule's standards of what 
constitutes individually identifiable information, a limited data set, 
and de-identified information (as defined under HIPAA), in order to 
address inconsistencies regarding these definitions and concepts 
between the HIPAA Privacy Rule and the Common Rule.
    More specifically, as described above, private information is not 
considered to be identifiable under the current Rule if the identity of 
the subject is not or may not be ``readily ascertained'' by the 
investigator from the information or associated with the information. 
In contrast, under the HIPAA Privacy Rule, health information is de-
identified and thus exempt from that rule only if it neither identifies 
nor provides a reasonable basis to believe that the information can be 
used to identify an individual. The HIPAA Privacy Rule provides two 
ways to de-identify information: (1) A formal determination by a 
qualified expert that the risk is very small that an individual could 
be identified; or (2) the removal of all 18 specified identifiers of 
the individual and of the individual's relatives, household members, 
and employers, as long as the covered entity has no actual knowledge 
that the remaining information could be used to identify the individual 
(45 CFR 164.514(b)).
    The HIPAA Privacy Rule addresses some informational risks by 
imposing restrictions on how individually identifiable health 
information collected by health plans, health care clearinghouses, and 
most health care providers (``covered entities'') may be used and 
disclosed, including for research. In addition, the HIPAA Security Rule 
(45 CFR parts 160 and, subparts A and C of part 164) requires that 
these entities implement certain administrative, physical, and 
technical safeguards to protect this information, when in electronic 
form, from unauthorized use or disclosure. However, the HIPAA Rules 
apply only to covered entities (and in certain situations to their 
business associates), and thus not all investigators are part of a 
covered entity and required to comply with those rules. Moreover, the 
HIPAA Rules do not apply specifically to biospecimens in and of 
themselves.
    Public comments in response to the 2011 ANPRM regarding covering 
all biospecimens raised a series of important concerns. A majority of 
the commenters opposed the ANPRM's suggested requirement of consent for 
research use of all biospecimens, regardless of identifiability, 
particularly if applied to samples collected before the effective date 
of the regulation. Some commenters cited lack of convincing evidence of 
harm caused by research use of non-identified clinical biospecimens 
without consent; they noted that they were not convinced that the 
principle of autonomy outweighs or trumps the principle of beneficence. 
They expressed concern that doing so would significantly slow advances 
in research and human health.
    Others acknowledged the erosion of public trust that can result 
from high-profile disputes involving the use of non-identified 
biospecimens collected during research.\43\ Commenters cited the costs 
to collect, log, and track consent status of data and biospecimens 
collected in a clinical setting to ensure that any restrictions on the 
research use of such resources were honored. However, it is important 
to note that it appears that many commenters were reacting to concerns 
that any change in the Common Rule with respect to consent for use of 
biospecimens would be applied retroactively--that is, to samples 
already collected.
---------------------------------------------------------------------------

    \43\ National Congress of American Indians. Havasupai Tribe and 
the lawsuit settlement aftermath. Retrieved on November 17, 2014, 
from http://genetics.ncai.org/case-study/havasupai-Tribe.cfm.
---------------------------------------------------------------------------

    Some patient advocacy organizations also expressed concerns about 
the consequences of requiring consent for the use of non-identified 
biospecimens. Other commenters noted that the recommendation to require 
consent might inappropriately give greater weight to the Belmont 
Report's principle of autonomy over the principle of justice, because 
requiring consent could result in lower participation rates in research 
by

[[Page 53944]]

minority groups and marginalized members of society. Yet, most of the 
comments from individual members of the public strongly supported 
consent requirements for use of their biospecimens, regardless of 
identifiability.
    Many commenters expressed the opinion that the existing regulatory 
framework is adequate and that current practices should be maintained, 
stressing that the research use of non-identified data or biospecimens 
does not involve risk to the research participant. Furthermore, several 
commenters noted that, although it is theoretically plausible to 
identify a person based on their biospecimen, the likelihood remains 
remote enough to argue against the presumption that the sources of all 
biospecimens are identifiable and cited a study showing that the risk 
of re-identification from a system intrusion of databases was only 
0.22%.\44\ In contrast, some commenters supported the idea of requiring 
consent for research use of all biospecimens, with one commenter noting 
simply that ``research use of data initially collected for non-research 
purposes should always require informed consent.''
---------------------------------------------------------------------------

    \44\ Kwok P et al. Harder Than You Think: A Case Study of Re-
Identification Risk of HIPAA-Compliant Records. NORC at The 
University of Chicago and Office of the National Coordinator for 
Health Information Technology. 2011. http://www.amstat.org/meetings/jsm/2011/onlineprogram/AbstractDetails.cfm?abstractid=302255.
---------------------------------------------------------------------------

    Several commenters stated that if the Common Rule were modified 
such that all biospecimens were covered under the rule regardless of 
identifiability there still might be some activities involving 
biospecimens that should be considered exempt or excluded from 
coverage. Suggestions included:

 Identifying markers for cancer prognosis or prediction of 
response to cancer therapy, or identifying cancer molecular targets 
(molecular research)
 Basic science research (including analysis of biological 
processes)
 Research on rare conditions and diseases
 Pediatric research
 Research with samples that lack potentially identifying 
information, such as serum or plasma not containing DNA
 Biospecimens lacking nucleic acids (such as certain red blood 
cells, expiratory gases)
 Blood culture bacteria
 Bacterial and viral specimens (this was listed in a comment as 
a public health issue)
 Protein analysis
 Statistical method development (to the extent that this 
development is related to biospecimens)
 New molecular methods to detect infectious agents
 Use of specimens to develop and validate new assays for 
infectious agents
 Archival paraffin blocks

    With respect to the 2011 proposal to adopt the HIPAA Privacy Rule's 
definition of identifiability, a majority of the public commenters 
strongly opposed the idea. They indicated that the HIPAA Privacy Rule's 
standard of identifiability would expand what is considered 
identifiable for purposes of the Common Rule and thus greatly impede 
relatively low-risk research without adding meaningful protections for 
human subjects. In particular, they asserted that the HIPAA standards 
were created to protect against disclosure of health information 
contained in medical records. As such, commenters argued, they are not 
appropriate for many types of research that would be covered by the 
Common Rule (e.g., behavioral and social science research). Others said 
this would be an extreme change in response to an as yet unidentified 
or clear problem. Commenters said that the information most at risk for 
inappropriate disclosure is the type of private health information that 
is already protected under the HIPAA Rules. Commenters feared that such 
a change in policy, while ``harmonizing'' the Common Rule to certain 
HIPAA standards, would create inordinate burdens in terms of new 
documentation requirements and result in a requirement to apply the 
HIPAA standards to all types of research, regardless of the level of 
risk.
d. NPRM Proposal
    Regardless of the scale on which harms may have occurred in the 
past, continuing to allow secondary research with biospecimens 
collected without consent for research places the publicly-funded 
research enterprise in an increasingly untenable position because it is 
not consistent with the majority of the public's wishes, which reflect 
legitimate autonomy interests. As such, one of the most fundamental 
changes proposed in this NPRM is to the definition of human subject 
(proposed Sec.  __.102(e)). The proposal is for the obtaining, use, 
study, or analysis of biospecimens to be covered under the Common Rule, 
regardless of identifiability. Covering biospecimens regardless of 
identifiability avoids codifying any given interpretation of the 
quickly evolving debates regarding whether certain analytic results 
(e.g., decoding the whole genome) should be considered to yield 
identifiable data. (Accompanying this proposal are some minor wording 
changes to other portions of that definition that are merely intended 
to clarify how the word ``obtains'' is currently interpreted by OHRP.)
    Thus, the focus of this proposal is to require informed consent for 
research involving biospecimens in all but a limited number of 
circumstances. The consent would not need to be obtained for each 
specific study using the biospecimen, but could instead be obtained 
through broad consent for future unspecified research (described in 
more detail in sections II.A.3.d and II.B of this preamble).
    An increase in trust and partnership is likely to increase 
participation rates in research; using individuals' samples and data 
without permission will hinder true partnership. Better communication 
and community engagement with patients, particularly in geographic 
areas and for population subgroups where consent rates are lower than 
average, should be a priority for the research community.
    In response to comments received about the 2011 ANPRM, the NPRM 
proposes to have the new definition of human subject apply 
prospectively, that is, it will only apply to research involving 
biospecimens that will be collected in the future. Additionally, in 
recognizing that this proposal will have major implications for the 
operational functioning of the research enterprise, compliance with 
this provision would be delayed until three years after publication of 
a final rule.
    Also consistent with comments received on the ANPRM, it is proposed 
that a subset of secondary research on stored biospecimens would be 
allowed without consent. Specifically, research designed to only 
generate information about the person that is already known would be 
considered outside of the scope of the Common Rule. This exclusion 
would include but not be limited to the development and validation of 
certain tests and assays (such as research to develop a diagnostic test 
for a condition using specimens from individuals known to have the 
condition and those known not to have the condition), quality assurance 
and control activities, and proficiency testing. This provision would 
be implemented through a new exclusion from the regulations at Sec.  
__.101(b)(3)(i), which has specifically been designed to reflect the 
underlying ethical principles.
    If the research is designed not to generate any new information 
about the

[[Page 53945]]

person, but only confirm something about them that is already known, 
then the interest in respecting the person's autonomy would appear to 
be relatively weak. As an example, imagine that a person is known to 
have a particular genetic disease, and the research involves evaluating 
a new product that might in a few minutes, at low cost, produce a 
result showing whether a person has that disease. The person's autonomy 
interest in whether or not such a study could take place would seem 
little different from that of anyone in a study that involved secondary 
use of identifiable information about them.
    In addition, the proposal permits IRBs to waive the requirement for 
informed consent, but the requirements for approval of such waivers 
would be very strict, and such waivers will only occur in rare 
circumstances. Note also that the exclusions proposed in Sec.  
;____.101(b)(1)(i), (iii)-(vi) would also allow for the use of 
biospecimens without consent in certain limited circumstances; these 
additional exclusions are discussed in section II.A.2 of this preamble, 
below.
    This proposal would not modify the Common Rule standard of 
identifiability (in contrast to what was discussed in the 2011 ANPRM). 
That is, the standard for determining when an investigator has 
sufficient information to readily ascertain the identity of an 
individual is not being changed under this proposal. Thus, coverage of 
information derived from biospecimens (whether or not the biospecimen 
was initially collected in the research or non-research context), or 
indeed any other type of information, would be the same under this 
proposal as is the case under the current Common Rule.
i. Alternative Proposals
    In this section, we discuss two alternative proposals, both of 
which maintain ``identifiability'' as the lynchpin for determining 
applicability of the Common Rule to biospecimens. These models increase 
transparency and opportunities for consent over and above what is 
provided for in the current Common Rule, but in a smaller set of 
circumstances than provided for under the primary proposal discussed 
above.

Alternative Proposal A: Expand the Definition of ``Human Subject'' To 
Include Whole Genome Sequencing (WGS)

    Rather than consider all research using biospecimens as 
constituting human subjects research, this alternative proposal would 
expand the definition of human subjects to include only specifically 
whole genome sequencing data, or any part of the data generated as a 
consequence of whole genome sequencing, regardless of the individual 
identifiability of biospecimens used to generate such data. Under this 
alternative, whole genome sequencing would be considered the sequencing 
of a human germline or somatic biospecimen with the intent to generate 
the genome or exome sequence of that biospecimen.
    Thus, under this alternative, the regulations would then apply both 
to research that would generate whole genome sequencing data, the use 
of any part of the generated data, and to research involving secondary 
use of any part of whole genome sequencing data that was originally 
generated for other purposes than the proposed research. Investigators 
conducting whole genome sequencing research could not avoid the need to 
comply with the Common Rule by removing identifiers from biospecimens 
or data, because whole genome sequence data in and of itself would meet 
the definition of human subject. Under this alternative, a new 
exemption would also be created that would allow such research to be 
considered exempt if consent to secondary future research use were 
obtained in accordance with proposed new requirements at Sec.  
__.116(c) and standards were met for protecting information and 
biospecimens as proposed at Sec.  __.105. A waiver of consent would be 
permitted, but would be modeled on the more stringent waiver criteria 
proposed for research involving biospecimens at Sec.  __.116(f)(2).
    Explicit consent to conduct research using whole genome sequencing 
data can be considered ethically important because such data can 
provide important insights into the health of individuals as well as 
their relatives. Moreover, whole genome sequence data gathered for one 
purpose may reveal important information, perhaps unanticipated and 
unplanned for, years later. Finally, whole genome sequence data are 
unique for each individual, or at the very least, highly unlikely to be 
the same as any other individual. Thus, the current allowable practice 
of removing identifiers from biospecimens and data to conduct whole 
genome sequencing research without consent might not sufficiently 
protect both the privacy and autonomy interests of the subject.
    As is currently the case, under this alternative, investigators' 
use of individually identifiable biospecimens, collected for purposes 
other than the currently proposed research study, would continue to be 
considered human subjects research. However, the secondary research use 
of non-identified information or non-identified biospecimens would 
continue to fall outside of the scope of the Common Rule, with the 
exception of whole genome sequence data as described above.
    One of the less obvious differences in scope between the primary 
proposal and this Alternative A relates to what research could be done 
with the data generated from whole genome sequencing that had taken 
place for clinical purposes. Under the primary proposal, the data 
produced by such sequencing could continue to be used for research, 
without additional consent, so long as it did not meet the definition 
of being identifiable private information. (HHS does not currently 
consider whole genome sequencing data to meet that definition for 
purposes of the Common Rule.) Under this Alternative A, consent would 
be required before using that data for research purposes.
    In contrast with the primary proposal in this NPRM, this 
Alternative Proposal A could be viewed as giving greater weight to the 
principle of beneficence, while giving less weight to the principle of 
respecting the autonomy of persons. It would require consent only for 
the type of studies that many people seem most concerned about (genomic 
research, including secondary use of genomic information that was 
produced for clinical purposes). And given that at the moment there is 
relatively little whole genome sequencing research taking place (in 
comparison to other types of biospecimen research; see section III.F of 
this preamble for more information), it would appear to currently 
impose a somewhat lesser burden in terms of obtaining and tracking 
consent than the main NPRM proposal.
    The major concern with this alternative proposal is that it would 
codify only a single technology as producing information that would be 
subject to the Common Rule, necessitating a re-evaluation of the scope 
of the Rule when technologies now in development to study, for 
instance, other ``omics,'' become more widespread.

Alternative Proposal B: Classifying Certain Biospecimens Used in 
Particular Technologies as Meeting the Criteria for ``Human Subject''

    This Alternative Proposal B would expand the definition of human 
subjects to include the research use of information that was produced 
using a

[[Page 53946]]

technology applied to a biospecimen that generates information unique 
to an individual such that it is foreseeable that, when used in 
combination with publicly available information, the individual could 
be identified. Information that met this standard would be referred to 
as bio-unique information. This proposal is conceptually very similar 
to Alternative Proposal A. The main difference is that the scope is 
somewhat broader: Whereas Alternative A requires consent for whole 
genome sequencing, Alternative B would require consent for genomic 
sequencing of even small portions of a person's genome, and also 
require consent for the use of other technologies that might be 
developed that similarly can generate information unique to a person.
    There are three separate conditions that would all need to be met 
before information would constitute bio-unique information: (1) It 
would have to have been produced by applying to a biospecimen a 
technology that is capable of producing information that is unique to 
an individual; (2) The technology would have to be used to produce 
enough information such that the information produced is likely to be 
unique to an individual; and (3) There would need to be publicly 
available information that, when combined with the information produced 
by the use of the technology, would create the possibility that some of 
the individuals whose biospecimens were analyzed using the technologies 
could be identified.
    The major concern with this alternative proposal is that, in order 
to make such a requirement responsive to scientific and technological 
developments, HHS would have to continually evaluate new technologies 
and the nature and amount of information produced using such 
technologies. Not only would this involve resources and expertise that 
may not be available to Federal departments and agencies, it would 
introduce ongoing uncertainty that may actually increase delays in 
important research.
e. What would change in the definition of ``human subject'' under the 
primary proposal?
     It is anticipated that the compliance date for the 
proposed expansion of the definition would be three years after the 
publication date. The main consequence of this change would be that 
informed consent (which could be broad, as described in sections 
II.A.3.d and II.B of this preamble) would generally be required before 
research use of biospecimens not covered by an exclusion.
     All biospecimens used for research purposes that do not 
fall under an exclusion (see proposed Sec.  __.101(b)(3)(i), and also 
Sec.  __.101(b)(1)(i), (iii)-(vi)) and are collected after the 
compliance date would be subject to the requirements of this rule, 
regardless of identifiability.
f. Questions for Public Comment
    2. Would providing a definition of biospecimen be helpful in 
implementing this provision? If so, how might the definition draw a 
line between when a biospecimen is covered by the Common Rule, and when 
processing of biological materials (e.g., to create a commercial 
product used for treatment purposes) has sufficiently altered the 
materials so that they should not be subject to the regulations? Would 
only covering biospecimens that include nucleic acids draw an 
appropriate line?
    3. To what extent do the issues raised in this discussion suggest 
the need to be clearer and more direct about the definition of 
identifiable private information? How useful and appropriate is the 
current modifier ``may be readily ascertained'' in the context of 
modern genomic technology, widespread data sharing, and high speed 
computing? One alternative is to replace the term ``identifiable 
private information'' with the term used across the Federal Government: 
Personally identifiable information (PII). The Office of Management and 
Budget's \45\ concept of PII refers to information that can be used to 
distinguish or trace an individual's identity (such as their name, 
social security number, biometric records, etc.) alone, or when 
combined with other personal or identifying information which is linked 
or linkable to a specific individual, such as date and place of birth, 
mother's maiden name, etc. It is acknowledged that replacing 
``identifiable private information'' with ``PII'' would increase the 
scope of what is subject to the Common Rule. However, the practical 
implications of such an expansion, other than the need to ensure that 
the data are security stored and otherwise protected against 
disclosure, may be minimal. Public comment is requested on the 
advantages and disadvantages of such a change.
---------------------------------------------------------------------------

    \45\ Executive Office of the President, Office of Management and 
Budget. (2007). Memorandum for the Heads of Executive Departments 
and Agencies. Retrieved from The White House: https://www.whitehouse.gov/sites/default/files/omb/memoranda/fy2007/m07-16.pdf.
---------------------------------------------------------------------------

    4. Which of the three proposals regarding the definition of human 
subject achieves the most reasonable tradeoff between the principles of 
autonomy (including transparency and level of trust) versus beneficence 
(as measured by facilitating valuable research)?
    5. Public comment is sought regarding any concerns that you have 
about each of the three proposals, including concerns about 
implementation or burden to investigators and institutions.
2. Explicit Exclusion of Activities From the Common Rule
    The NPRM creates a new section in the regulations referred to as 
``exclusions.'' This section outlines eleven specific types of 
activities that will be outside the scope of the regulations. These 
activities will therefore not have to satisfy any regulatory 
requirements, nor is it expected (unlike exempt research) that they 
will undergo any type of review process to determine this status. The 
exclusions will eliminate uncertainty regarding some activities that 
are not research, and identify some activities that arguably might be 
judged to be research, but whose contribution to public welfare is so 
imperative that they should proceed without having to satisfy the 
regulatory requirements. The exclusions also identify certain research 
activities that are sufficiently low-risk and nonintrusive that the 
protections provided by the regulations are an unnecessary use of time 
and resources, whereas the potential benefits of the research are 
substantial.
    The Common Rule has been criticized for not being clear about how 
to interpret what activities are covered by the policy and for 
inappropriately being applied to and inhibiting certain activities. The 
first six exclusion categories are for activities that are deemed not 
to be research for the purposes of this policy, without needing to 
consider whether the regulatory definition applies. The definition of 
research does not provide such a clear and precise way of 
distinguishing among similar activities that it is immediately obvious 
which activities fall under the definition and which do not. By 
creating exclusion categories that are deemed not research, these 
activities are more clearly distinguished as not having to satisfy the 
regulatory requirements.
    Three of the exclusions seek to eliminate any uncertainty about 
whether certain internal program improvement activities, historical or 
journalistic inquiries, or quality assurance or improvement activities 
satisfy the definition of research. The other three exclusions include 
some

[[Page 53947]]

activities that fall into to a gray area that encompasses some 
activities that arguably might be judged to be research, but that are 
part of inherently governmental functions that have purposes other than 
research, such as responsibilities to protect public health and welfare 
(see exclusions for criminal investigations, public healthy 
surveillance, and intelligence surveillance). These activities promote 
recognized specific goods that are crucial to the public welfare, and 
should be carried out without any hindrances that satisfying regulatory 
requirements might impose. For these activities, the principles of 
beneficence and justice outweigh any intrusions on individual autonomy 
that the regulations might have prevented.
    The next four categories of proposed exclusions are for activities 
that are considered low-risk either in themselves or because there are 
appropriate safeguards already in place independent of the Common Rule. 
Here the level of risk, the potential benefits, and the nature of human 
participation in this research are such that the principle of 
beneficence determines that the research activities may go forward 
without the need to impose the protections of the Common Rule.
    The last exclusion applies to research involving the secondary use 
of non-identified biospecimens when the research is limited to 
generating information about the subject that is already known. As 
such, this research does not need any additional protections provided 
by these regulations and the potential benefits of this research 
justify it under the principle of beneficence. Because this exclusion 
directly relates to the proposed changes in the definition of ``human 
subject'' to include all biospecimens, it is discussed above in section 
II.A.1 of this preamble.
    It should be noted that the fact that the NPRM now specifically 
includes a list of certain excluded activities should not be seen as 
altering the fact that many other activities that do not meet the 
criteria for being subject to the Common Rule remain outside the scope 
of the rule. For example, an activity that does not meet the regulatory 
definition of research, or does not involve human subjects, would still 
not be subject to these regulations.
    Currently, the Common Rule excludes from coverage (1) activities 
that do not meet the definition of research (Sec.  __.102(d) of the 
current Rule); (2) activities that are not described as research 
subject to regulation (Sec.  __.102(e) of the current Rule); and (3) 
activities that do not involve a human subject (Sec.  __.102(f) of the 
current Rule).
    The ANPRM asked questions about the definition of research and 
whether various activities should be excluded from the Common Rule, 
either by changing the definition of research or by adding exemptions, 
or both. The ANPRM sought comment on whether and, if so, how, the 
Common Rule should be changed to clarify whether quality improvement 
activities, program evaluation studies, or public health activities are 
covered. It also asked whether there are specific types of studies for 
which the existing rules are inappropriate. If so, comments were sought 
on whether this problem should be addressed through modifications to 
the exemption categories, or by changing the definition of ``research'' 
used in the Common Rule to exclude some of these studies, or a 
combination of both.
    If the definition of research were to be changed, public comment 
was sought on how excluded activities should be defined (e.g., 
``quality improvement'' or ``program evaluation''). With regard to 
quality improvement activities, the public was asked to comment on 
whether it might be useful to adopt the distinction made by the HIPAA 
Privacy Rule, which distinguishes between ``health care operations'' 
and ``research'' activities, defining ``health care operations'' to 
include, among other activities, ``conducting quality assessment and 
improvement activities, including outcomes evaluation and development 
of clinical guidelines, provided that the obtaining of generalizable 
knowledge is not the primary purpose of any studies resulting from such 
activities.''
a. Exclusion of Activities that are Deemed Not Research (NPRM at Sec.  
__.101(b)(1))
    The first set of six exclusions involve activities that will be 
excluded from the regulations because they will be deemed to not 
involve research. Three of the first six exclusions (discussed in 
sections II.A.1.a.i, ii, and iv, below) provide clarity regarding the 
applicability of the Common Rule to activities about which institutions 
have raised questions in the past as to whether these activities meet 
the regulatory definition of research. These exclusions aim to reduce 
the time and effort involved trying to determine whether the 
regulations apply, and in unnecessary reviews of these activities.
    The other three of these exclusions (discussed in sections 
II.A.1.iii, v, and vi below) apply to activities that are largely 
inherently government functions that have purposes other than research, 
and, when conducted by a government employee or contractor, are subject 
to a variety of other statutes, regulations, and polices that are 
designed to protect individual privacy and data security, as well as 
provide notice to those providing the information as to the uses to 
which the information will be put (see, for example, the Privacy Act of 
1974). These activities promote recognized specific goods that are 
crucial to the public welfare, and because of this they should be 
carried out without any hindrances that satisfying the Common Rule 
regulatory requirements might impose. For these activities, the 
principle of beneficence outweighs any intrusions on individual 
autonomy that the regulations might have prevented, and this allows 
these important activities to proceed without delay.
    The ANPRM asked whether various activities such as quality 
improvement, public health activities, or program evaluations studies 
should be excluded from the rule.
i. Program Improvement Activities (NPRM at Sec.  __.101(b)(1)(i))
(1) NPRM Proposal
    The first exclusion, proposed in the NPRM at Sec.  __.101(b)(1)(i), 
is for data collection and analysis, including the use of biospecimens, 
for an institution's own internal operational monitoring and program 
improvement purposes, if the data collection and analysis is limited to 
the use of data or biospecimens originally collected for any purpose 
other than the currently proposed activity, or is obtained through oral 
or written communications with individuals (e.g., surveys or 
interviews). This category is excluded because these activities are 
designed for various administrative purposes related to using 
information to improve the quality of services provided by a specific 
institution, and are not designed to produce generalizable knowledge. A 
majority of commenters to the 2011 ANPRM supported excluding program 
evaluation activities from the scope of the Common Rule. Many of these 
commenters argued that the public benefits resulting from this type of 
activity justified its practice, particularly given the generally low-
risk involved.
    An example of an activity that would satisfy this exclusion is a 
survey of hospital patients to evaluate and improve the quality of 
meals delivered to hospital patients. An example of an activity that 
would not satisfy this exclusion is a prospective observational

[[Page 53948]]

study of patient treatments to analyze the comparative effectiveness of 
two different standard of care treatments frequently used to treat the 
same medical condition.
(2) Questions for Public Comment
    6. Public comment is sought for whether this excluded activity 
should simply be discussed in the text of the final rule's preamble, 
and guidance produced to assist investigators in making such a 
determination, or whether any other similar exclusions should be 
addressed.
    7. Public comment is sought for whether biospecimens should not be 
included in any of these exclusion categories, and if so, which ones.
ii. Oral History, Journalism, Biography, and Historical Scholarship 
Activities (NPRM at Sec.  __.101(b)(1)(ii))
(1) ANPRM Discussion
    The ANPRM asked whether there were any fields of study (such as 
classics, history, languages, literature, and journalism) whose usual 
methods of inquiry were not intended to or should not be covered by the 
Common Rule.
(2) NPRM Proposal
    The second proposed exclusion, in the NPRM at Sec.  
__.101(b)(1)(ii) is for oral history, journalism, biography and 
historical scholarship activities that focus directly on the specific 
individuals about whom the information is collected.
    The overwhelming majority of public comments to the 2011 ANPRM 
responding to the question about excluding specific fields of study 
from the regulatory requirements of the Common Rule supported 
explicitly excluding certain activities from the definition of research 
versus modifying the exemption categories. The overwhelming majority of 
these comments focused on oral history. Some of the comments were 
virtually identical and appear to have been coordinated. Many of the 
comments reflected the view that the Common Rule was not designed or 
intended to include oral history activities, and that the ethical codes 
pertaining to oral history procedures are not consistent with the 
application of the ethical principles reflected in the Common Rule.
    A smaller number of similar comments were submitted with respect to 
various humanities disciplines and journalism. A significant minority 
of commenters opposed the exclusion of any fields of study, arguing 
that the activity itself rather than the academic discipline or 
training of the investigator should be the basis for the assessment of 
whether the activity should be excluded. Some of the commenters 
recommended that the definition of research be focused more explicitly 
by being limited to ``biomedical and behavioral research,'' in 
accordance with the statutory provision underlying the Common Rule. A 
significant number of commenters recommended that guidance should be 
issued to clarify how the definition of research should be applied, 
with cases and explanations.
    While the NPRM does not propose to modify the definition of 
``research'', it does propose to explicitly exclude oral history, 
journalism, biography, and historical scholarship activities that focus 
directly on the specific individuals about whom the information or 
biospecimens is collected. In the kinds of activities referred to here, 
the ethical requirement is to provide an accurate and evidence-based 
portrayal of the individuals involved, and not to protect them from 
public scrutiny. Therefore, the protections afforded to individuals by 
the Common Rule seem unhelpful in furthering the aforementioned ethical 
goal in this context. Additionally, these fields of research have their 
own codes of ethics, according to which, for example, consent is 
obtained for oral histories. It is believed that because of these 
reasons, explicit exclusion of these activities from the scope of the 
Common Rule is appropriate.
iii. Criminal Justice Activities (NPRM at Sec.  __.101(b)(1)(iii))
(1) NPRM Proposal
    The third category of activities that the NPRM excludes from the 
proposed rule encompasses data collection and analysis that enables the 
uniform delivery of criminal justice. The scope of this exclusion is 
collection and analysis of data, biospecimens, or records by or for a 
criminal justice agency for activities authorized by law or court order 
solely for criminal justice or criminal investigative purposes. The 
activities excluded are necessary for the operation and implementation 
of the criminal justice system.
    The provision would essentially codify current Federal 
interpretation that such activities are not deemed to be research under 
the Common Rule. The addition of this provision is designed to avoid 
the imposition of disparate requirements by IRBs with overlapping 
jurisdiction when a data collection or analysis activity encompasses 
the development of methods required by law or court order for criminal 
justice or criminal investigative purposes. For example, the Federal 
Bureau of Investigation (FBI) is charged by law with setting standards 
governing the collection and processing of DNA biospecimens and 
information taken (forcibly if necessary) from certain federal and 
state criminal offenders incident to their arrest or conviction for 
prescribed offenses under the National DNA Identification Act of 1994 
and other acts. Similarly, the FBI is charged by law with setting 
standards governing the collection and processing of fingerprints and 
related biographical information taken from federal and state criminal 
offenders and certain sensitive civil employment applicants. At the 
same time, through its Laboratory Division and other components the FBI 
routinely collects human biospecimens at crime scenes from or relating 
to victims and offenders both known and unknown. Incident to these 
activities, the FBI is also charged with maintaining, and 
authenticating through identification processes, the criminal record 
history information of criminal offenders for the Federal Government 
and for the overwhelming majority of state governments who elect to 
participate and share information through those FBI systems.
iv. Quality Assurance and Quality Improvement Activities (NPRM at Sec.  
__.101(b)(1)(iv))
(1) NPRM Proposal
    The fourth category of excluded activities covers quality assurance 
or improvement activities involving the implementation of an accepted 
practice to improve the delivery or quality of care or services 
(including, but not limited to, education, training, and changing 
procedures related to care or services) if the purposes are limited to 
altering the utilization of the accepted practice and collecting data 
or biospecimens to evaluate the effects on the utilization of the 
practice. This exclusion does not cover the evaluation of an accepted 
practice itself.
    As an example of an activity that would satisfy this exclusion, 
assume that there is an accepted practice that is known to reduce the 
likelihood of an infection after the insertion of a central line. A 
randomized study in which half the participating institutions would be 
assigned to have the staff undergo an educational intervention about 
the need to use that accepted practice, and the other half would not 
undergo that intervention, would satisfy this exclusion, since it would 
only be intended to see if the intervention resulted in greater use of 
the accepted practice. In contrast, imagine a different study that was 
designed to determine

[[Page 53949]]

how well that accepted practice, when it is used, reduces infections. 
That study would not satisfy this exclusion, since it would be studying 
the effectiveness of the practice itself, in contrast to studying an 
effort to increase use of the practice.
    Over the past several years, including in response to the 2011 
ANPRM, OHRP has received comments from many individuals and 
organizations expressing concern that some readings of the definition 
of ``research'' would imply that the regulations apply to quality 
improvement activities, thereby potentially interfering with the 
ability of health care and other professionals to enhance the delivery 
or quality of care or services involving the use of accepted practices. 
Indeed, a majority of commenters to the 2011 ANPRM supported excluding 
quality improvement activities from the scope of the Common Rule. These 
quality improvement activities are in many instances conducted by 
health care and other organizations under clear legal authority to 
change internal operating procedures to increase safety or otherwise 
improve performance, often without the consent of staff or clients, 
followed by monitoring or evaluation of the effects. These activities 
are generally conducted in circumstances where independent privacy, 
confidentiality, and security safeguards are in place, minimizing the 
chances of harm. These efforts, some of which could be judged to be 
research, should be carried out because of the recognized public good 
they achieve. This exclusion is intended to avoid impeding such efforts 
where the Common Rule's requirements might have a chilling effect on 
the ability to learn from, and conduct, important types of innovation.
    Recognizing that some quality improvement efforts should not be 
considered to involve research as it is defined in the Common Rule can 
allay many of these concerns. Thus, this exclusion is being proposed to 
deal with quality improvement activities that are aimed at implementing 
practices that are already accepted, with the goal of improving the 
delivery or quality of treatments or services. This exclusion would 
permit measuring and reporting provider performance data for practice 
management, clinical, or administrative uses. As proposed, this 
exclusion does not include evaluations of different accepted practices 
themselves, however, such as activities designed to determine whether a 
particular accepted medical treatment is or is not more effective than 
another.
    This provision also covers quality improvement activities that are 
not related to delivery of patient care, but rather involve the 
delivery or quality of other public benefit or social services. For 
example, institutions and other entities may provide social services, 
educational offerings, or other beneficial activities where there is 
empirical evidence of the value of those efforts, and they may wish to 
evaluate different ways of enhancing the delivery or quality of those 
existing services. This exclusion has been written broadly to include 
such activities.
    The rationale for this excluded category is that these activities 
are designed only to improve the implementation of a practice that is 
already accepted, not to evaluate the effectiveness and value of the 
accepted practice itself, and thus would generally be expected to pose 
little if any risks to the recipients of those practices, and are 
directly aimed at improving the practical use of those practices. This 
does not include quality improvement activities designed with a 
research purpose relating to the safety and efficacy of the accepted 
practice. It is accordingly important to note that activities that do 
involve such research--for example, assigning patients to different 
versions of treatments that are within the standard of care in order to 
evaluate the differences between those treatments in terms of 
effectiveness or risks--would not come within this exclusion. In the 
educational context, for example, activities where students are 
assigned to experimental and control groups to determine the 
effectiveness of experimental teaching methodologies would also not 
come within this exclusion. Furthermore, that type of activity would 
also not meet a separate requirement of this exclusion--that the 
activity be related to the delivery of (i.e., implementing) an accepted 
form of care, and not an attempt to evaluate the efficacy or risks of 
that form of care.
v. Public Health Surveillance (NPRM at Sec.  __.101(b)(1)(v))
(1) NPRM Proposal
    The fifth category of excluded activities involves public health 
surveillance activities, including the collection and testing of 
biospecimens, conducted, supported, requested, ordered, required, or 
authorized by a public health authority and limited to those necessary 
to allow the public health authority to identify, monitor, assess, or 
investigate potential public health signals or the onset of a disease 
outbreak, including trends, or signals, and patterns in diseases, or 
sudden increase in injuries from using a consumer product, or 
conditions of public health importance, from data, and including those 
associated with providing timely situational awareness and priority 
setting during the course of an event or crisis that threatens public 
health, including natural or man-made disasters. A majority of 
commenters to the 2011 ANPRM supported excluding public health 
activities from the scope of the Common Rule.
    The rationale for excluding some public health surveillance 
activities is that when a public health authority conducts public 
health surveillance activities to fulfill its legal mandate to protect 
and maintain the health and welfare of the populations it oversees, the 
regulatory protections of the Common Rule should not impede its ability 
to accomplish its mandated mission of promoting this recognized public 
good, in keeping with the principle of beneficence. Other protections 
independent of the Common Rule exist that serve to protect the rights 
and welfare of individuals participating in such activities, including 
privacy, confidentiality and security safeguards for the information 
collected.
    Public health surveillance refers to the collection, analysis, and 
use of data to target public health prevention. It is the foundation of 
public health practice. Surveillance uses data from a variety of 
sources, including mandatory reporting of certain conditions, routine 
monitoring, vital records, medical billing records, and public health 
investigations in response to reports of potential outbreaks. The line 
between public health surveillance and epidemiological research can be 
difficult to draw, as the same techniques may be used in both. 
Generally, the difference between the activities is the purpose or 
context in which the investigation is being conducted and the role of 
the public health authority.
    The following are examples of activities that meet the public 
health surveillance exclusion:
     Safety and injury surveillance activities designed to 
enable a public health authority to identify, monitor, assess, and 
investigate potential safety signals for a specific product or class of 
products (for example, the surveillance activities of the FDA's Adverse 
Event Reporting System (AERS), the Vaccine Adverse Event Reporting 
System (VAERS), Manufacturer and User Facility Device Experience 
(MAUDE) database, the Medical Product Safety Network (MedSun), and the 
Sentinel Initiative);
     Surveillance activities designed to enable a public health 
authority to identify unexpected changes in the

[[Page 53950]]

incidence or prevalence of a certain disease in a defined geographic 
region where specific public health concerns have been raised (e.g., 
the U.S. influenza surveillance system, which allows CDC to find out 
when and where influenza activity is occurring, track influenza-related 
illness, determine what influenza viruses are circulating, detect 
changes in influenza viruses, and measure the impact influenza is 
having on hospitalizations and deaths in the United States);
     Surveillance activities designed to enable a public health 
authority to identify the prevalence of known risk factors associated 
with a health problem in the context of a domestic or international 
public health emergency;
     Surveillance activities designed to enable a public health 
authority to locate the range and source of a disease outbreak or to 
identify cases of a disease outbreak;
     Surveillance activities designed to enable a public health 
authority to detect the onset of disease outbreaks or provide timely 
situational awareness during the course of an event or crisis that 
threatens the public health, such as a natural or man-made disaster.
    On the other hand, subsequent research using information collected 
during a public health surveillance activity, for instance genetic 
analysis of biospecimens, would not fall under this exclusion, but 
would likely be covered under one or more of the other exclusions for 
low-risk research or exemptions.
    Additional examples of activities that would not fall under the 
exclusion include: Exploratory studies designed to better understand 
risk factors, including genetic predisposition, for chronic diseases; 
exploratory studies designed elucidate the relationships between 
biomarkers of exposure and biomarkers of disease; exploratory studies 
of potential relationships between behavioral factors (e.g., diet) and 
indicators of environmental exposures. These types of activities would 
be considered research, and thus subject to the Common Rule, even if 
conducted by a Federal agency with a public health mandate. To clarify 
this proposed exclusion the NPRM also proposes a new regulatory 
definition of public health authority proposed in Sec.  __.102(k).
(2) Question for Public Comment
    8. Public comment is requested on whether the parameters of the 
exclusions are sufficiently clear to provide the necessary operational 
guidance, or whether any additional criteria or parameters should be 
applied to clarify or narrow any of these exclusions.
vi. Intelligence Surveillance Activities (NPRM at Sec.  
__.101(b)(1)(vi))
(1) NPRM Proposal
    The sixth category of excluded activities that will not be 
considered research involves surveys, interviews, surveillance 
activities and related analyses, or the collection and use of 
biospecimens where these activities are conducted by a defense, 
national security, or homeland security authority solely for authorized 
intelligence, homeland security, defense, or other national security 
purposes.
    The rationale for excluding the defense or national security-
related activities is similar to that described above regarding public 
health surveillance activities. The lawful conduct of the departments' 
and agencies' mandated missions for actively protecting national 
security, homeland security, and homeland defense are fundamentally not 
research. These activities may incorporate the collection and analysis 
of identifiable information, but they are not designed to develop or 
contribute to generalizable knowledge; rather, they are solely 
conducted to fulfill a department or agency's legal mandate to ensure 
the safety and protection of the United States, its people, and its 
national security interests. This exclusion codifies the current 
interpretation of the Common Rule. Research conducted or sponsored by 
Federal departments and agencies using this exclusion will continue to 
be subject to this regulation.
b. Exclusion of Activities That Are Low-Risk and Already Subject to 
Independent Controls (NPRM at Sec.  __.101(b)(2))
i. NPRM Goals
    The NPRM proposes to exclude four categories of research activities 
that do not entail physical risk and are non-intrusive, either in 
themselves or because they are subject to policies that provide 
oversight independent of the Common Rule. Although the activities are 
research, they will not be required to receive any form of 
determination or IRB approval--including expedited review. 
Additionally, statements of purpose, benefit, and voluntariness as well 
as consent are not required unless the entity conducting the research, 
collecting data, or providing data is also subject to separate statutes 
and regulations requiring such statements. Some of the activities 
proposed for exclusion are categories that appear as exemptions in the 
current Rule. It is proposed that the marginal protections provided by 
the Common Rule are not consistent with the amount of researcher time 
and institutional resources that they currently draw.
    By reclassifying certain research activities from being exempt to 
being excluded, the proposed rule would eliminate the need for any 
administrative or IRB review. All investigators performing excluded 
studies are expected to act in a way that is consistent with the 
principles outlined in the Belmont Report, even if the Common Rule does 
not impose requirements on excluded work. For instance, consistent with 
the spirit of respect for persons, investigators should tell 
prospective subjects the purpose of the information collection and, 
where appropriate, that they can choose to participate or not in these 
activities, although investigators are not explicitly required to do 
so.
    Designating certain research fully outside of the bounds of the 
Common Rule means that investigators are self-determining whether their 
own research is covered by the law. As such, the proposal to add these 
categories is based on the assumption that all investigators will be 
accurately determining whether their proposed activity is outside the 
scope of the Common Rule. There is no current proposal outlining how 
decisions will be made for determining whether a research activity is 
eligible for exclusion and by whom or how differences among 
collaborators would be handled. As readers review each of the exclusion 
categories below, please consider whether the benefits associated with 
reducing the delay for researchers are countervailed by potential 
increases in risk of harm.
    Throughout this NPRM, the term ``low-risk'' is used to denote 
research activities that do not entail physical risk, and where both 
the probability and magnitude of other risks, once required protections 
are applied, are hypothesized to be low. Public comment is sought on 
whether there are instances in the regulatory text where the term 
``low-risk'' is used, but these conditions do not apply, and whether 
there is a better way to characterize this category of risk.
ii. ANPRM Discussion
    The ANPRM discussed criticisms of the current rule that it does not 
adequately calibrate the review process to the level of risk of the 
research, particularly in social and behavioral research. It also 
discussed whether answering questions should be sufficient indication 
of willingness to participate in survey or interview

[[Page 53951]]

research. It distinguished between informational or psychological risks 
and physical risks, and raised questions about how effectively IRB 
review provides protections from informational or psychological risks.
iii. Educational Tests, Survey Procedures, Interview Procedures, or 
Observation of Public Behaviors (NPRM at Sec.  __.101(b)(2)(i))
(1) NPRM Proposal
    The exclusion at Sec.  __.101(b)(2)(i) is for research, not 
including interventions, that involves the use of educational tests 
(cognitive, diagnostic, aptitude, achievement), survey procedures, 
interview procedures, or observation of public behavior (including 
visual or auditory recording) uninfluenced by the investigators, if at 
least one of the following is met:
     The information is recorded by the investigator in such a 
manner that human subjects cannot be identified, directly or through 
identifiers linked to the subjects; or
     Any disclosure of the human subjects' responses outside 
the research would not reasonably place the subjects at risk of 
criminal or civil liability or be damaging to the subjects' financial 
standing, employability, educational advancement, or reputation; or
     The research will involve a collection of information 
subject to the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq., 
research information will be maintained on information technology that 
is subject to and in compliance with section 208(b) of the E-Government 
Act of 2002, 44 U.S.C. 3501 note, and all of the information collected, 
used, or generated as part of the research will be maintained in a 
system or systems of records subject to the Privacy Act of 1974, 5 
U.S.C. 552a.
    The exclusion does not include research activities in which any 
sort of intervention is used, in addition to the specified methods of 
information collection. Also, the term ``survey'' as used here refers 
to information collected about individuals via questionnaire or similar 
procedures (e.g., the Current Population Survey conducted by the 
Census). ``Human subjects'' do not include organizations or businesses. 
``Survey,'' as used here, does not include the collection of 
biospecimens or other types of information collection that might 
involve invasive procedures. Thus, a survey that included information 
collections in addition to verbal or written responses, including the 
collection of a biospecimen or the use of some other physically 
invasive procedures (e.g., a diagnostic test and blood spot or buccal 
swab) could not use this exclusion.
    This exclusion includes the research activities in current 
exemption category 2 in the (current Common Rule at Sec.  
__.101(b)(2)), and some additional government information collection 
research activities using the same methods. As in the current exemption 
category 2, this proposed exclusion includes research studies whose 
methods consist of the use of educational tests, survey procedures or 
interview procedures, or observation of public behavior uninfluenced by 
the investigators, if the data are recorded anonymously, or the 
information is recorded with identifiers, but is not sensitive such 
that its disclosure could result in harm to the subjects. The exclusion 
provides a list of the specific harms that must be considered, which is 
the same as in the current exemption category, with the addition of the 
specific harm of being damaging to the subjects' educational 
advancement. This potential harm has been added because of the obvious 
relevance to the effects of the disclosure of responses in research 
involving educational tests.
    This proposed exclusion does not include the first element in the 
current exemption category at Sec.  __.101(b)(3)(i), which is the 
element pertaining to research involving the use of educational tests, 
survey procedures, interview procedures, or observation of public 
behavior if the human subjects are elected or appointed public 
officials or candidates for public office. The rationale for this 
change in the proposed NPRM is that it does not seem appropriate to 
single out this category of subjects for different treatment in this 
way.
    The third element of this proposed exclusion covers research 
activities using the same methods identified above even when the data 
are recorded with identifiers and the information recorded may be 
personally sensitive or private but not explicitly damaging to an 
individual, if the research is subject to specified federal statutes 
and regulations that require data security and subject privacy 
protections. Under this proposal, the preponderance of research 
conducted by Federal employees and contractors that collects 
information exclusively through educational tests, questionnaires, or 
observations of behavior would no longer be subject to the Common Rule 
because most such collections would be subject to the Paperwork 
Reduction Act of 1995, would be maintained on information technology 
that is subject to and in compliance with section 208(b) of the E-
Government Act of 2002, and all of the information collected, used, or 
generated as part of the research would be maintained in a system or 
systems of records subject to the Privacy Act of 1974. Furthermore, 
consistent with these laws, OMB's Standard 2.2 in its ``Standards and 
Guidelines for Statistical Surveys'' \46\ identifies the required 
notifications to potential survey respondents.
---------------------------------------------------------------------------

    \46\ Executive Office of the President, OMB. (Sept. 2006). 
Standards and Guidelines for Statistical Surveys. Retrieved from The 
White House: https://www.whitehouse.gov/sites/default/files/omb/inforeg/statpolicy/standards_stat_surveys.pdf.
---------------------------------------------------------------------------

    Specifically, Standard 2.2 states that Federal agencies must ensure 
that each information collection instrument clearly states the reasons 
the information is planned to be collected; the way such information is 
planned to be used to further the proper performance of the functions 
of the agency; whether responses to the collection of information are 
voluntary or mandatory (citing authority); the nature and extent of 
confidentiality to be provided, if any (citing authority); an estimate 
of the average respondent burden together with a request that the 
public direct to the agency any comments concerning the accuracy of 
this burden estimate and any suggestions for reducing this burden; the 
OMB control number; and a statement that an agency may not conduct and 
a person is not required to respond to an information collection 
request unless it displays a currently valid OMB control number. These 
policies are rooted in the Fair Information Practice Principles that 
cover the following concepts: Individual participation, transparency, 
authority, purpose specification and use limitation, minimization, 
access and amendment, redress, quality and integrity, security, 
training, integration, and accountability. It is proposed that the 
information risk protections afforded by these laws and their 
implementing regulations are generally stronger than the privacy 
protections that result from IRB review, and would result in affording 
more uniform protections to participants.
    The rationale for excluding these research activities from the 
Common Rule, even when the research is not otherwise subject to 
additional federal controls, is that consent is inherent to 
participation and that the risks most likely to be experienced by 
subjects are related to disclosure of anonymous, non-sensitive 
information and are thus categorized as ``low.'' Said another way, all 
individuals, including vulnerable populations, would understand that 
actively providing response to

[[Page 53952]]

educational tests, surveys, or interview procedures constitutes consent 
to participate and that the risk associated with such participation 
would be related to disclosure of the information they provided. The 
exclusion of this type of activity rests in large part on the idea that 
all individuals, regardless of the setting or context in which the 
activity will take place, are generally familiar with common forms of 
educational tests, survey and interview procedures which they 
experience in their daily lives, and do not need additional measures to 
protect themselves and their privacy from investigators who seek their 
involvement in research activities involving these procedures.
    This exclusion is based on the assumption that the activities 
covered by this category are largely informational, and thus the most 
important role that an IRB might play with respect to reducing 
potential harms is to ensure data security and privacy protections. 
Under this assumption, the proposed exclusion is consistent with the 
principle of respect for persons and the preservation of autonomy. In 
the case of observation of public behavior, even if the subject does 
not know that an investigator is watching his or her actions, the 
subject's behavior is public and could be observed by others and thus 
the research observation is not inappropriately intrusive. However, 
there are situations in which this assumption would not always hold. 
For instance, administration of a questionnaire or participation in a 
focus group on a sensitive topic may induce significant stress in some 
individuals, or individuals approached about taking a survey may feel 
compelled to participate. Whether and how the exclusion should be 
bounded so that the final rule achieves a balance among the principles 
of beneficence, autonomy, and justice is the subject of the request for 
comment on this proposed exclusion.
    In addition, this exclusion is in keeping with one of the goals of 
this NPRM, namely to reduce burden on research that includes sufficient 
protections to research subjects. By proposing that this exclusion 
could be satisfied if the information to be collected is subject to the 
Paperwork Reduction Act of 1995, would be maintained on information 
technology that is subject to and in compliance with section 208(b) of 
the E-Government Act of 2002, and all of the information collected, 
used, or generated as part of the research would be maintained in a 
system or systems of records subject to the Privacy Act of 1974, the 
NPRM notes that the privacy protections afforded by these laws are 
generally comparable, if not stronger, than the privacy protections 
that result from IRB review.
(2) Questions for Public Comment
    9. Public comment is requested on the extent to which covering any 
of these activities under the Common Rule would substantially add to 
the protections provided to human research subjects.
    10. Public comment is sought on whether this exclusion should only 
apply to research activities in which notice is given to prospective 
subjects or their legally authorized representatives as a regulatory 
requirement. If so, please comment on what kind of information should 
be included in the notice such as the research purpose, privacy 
safeguards, contact information, ability to opt-out, etc. Would 
requiring notice as a condition of this exempt research strike a good 
balance between autonomy and beneficence?
    11. Public comment is sought regarding whether it is reasonable to 
rely on investigators to make self-determinations for the types of 
research activities covered in this particular exclusion category. If 
so, should documentation of any kind be generated and retained?
    12. Public comment is sought regarding whether some or all of these 
activities should be exemptions rather than exclusions.
    13. Public comment is sought regarding whether these exclusions 
should be narrowed such that studies with the potential for 
psychological risk are not included. Are there certain topic areas of 
sensitive information that should not be covered by this exclusion? If 
so, please provide exemplary language to characterize such topic areas 
in a manner that would provide clarity for implementing the Rule.
    14. For activities captured under the third element of this 
exclusion, do the statutory, regulatory, and other policy requirements 
cited provide enough oversight and protection that being subject to 
expedited review under the Common Rule would produce minimal additional 
subject protections? If so, should the exclusion be broadened to also 
cover secondary analysis of information collected pursuant to such 
activities?
    15. Public comment is requested on the extent to which excluding 
any of these research activities from the Common Rule could result an 
actual or perceived reduction or alteration of existing rights or 
protections provided to human research subjects. Are there any risks to 
scientific integrity or public trust that may result from excluding 
these research activities from the Common Rule?
iv. Research Involving the Collection or Study of Information that has 
been or will be Collected (NPRM at Sec.  __.101(b)(2)(ii))
(1) Current Rule
    This exclusion appears in the current Common Rule as exemption 
category 4 (current Rule at Sec.  __.101(b)(4)). This exemption 
currently applies to research involving the use of existing data, 
documents, records, and pathological or diagnostic specimens, but only 
if the sources are publicly available or if the information is recorded 
by investigators in such a manner that subjects cannot be identified, 
directly or through identifiers linked to them.
(2) ANPRM Discussion
    The ANPRM proposed retaining this exemption as an exemption (not an 
exclusion). The ANPRM asked questions about whether the current 
limitations specified in exempt category 4 (research involving the use 
of existing information or biospecimens, Sec.  __.101(b)(4) in the 
current Rule) should be eliminated. Specifically, the ANPRM suggested 
that the category would be revised to eliminate the word ``existing.'' 
With this elimination, the exemption would be broadened to cover the 
use of information or biospecimens that were or will be collected for 
purposes other than the suggested research, rather than requiring that 
all of the information or biospecimens already exist at the time the 
study is suggested for exemption.
(3) NPRM Proposal
    The second category of low-risk research activities excluded from 
the proposed rule is a revised version of the current Rule's exemption 
category 4 (current Rule at Sec.  __.101(b)(4)). The NPRM proposal is 
that the excluded category at Sec.  __.101(b)(2)(ii) includes research 
involving the collection or study of information that has been or will 
be acquired solely for non-research activities or was acquired for 
research studies other than the proposed research study when the 
sources are publicly available, or the information is recorded by the 
investigator in such a manner that human subjects cannot be identified, 
directly or through identifiers linked to the subjects, the 
investigator does not contact the subjects, and the investigator will 
not re-identify subjects or otherwise conduct an analysis that could 
lead to

[[Page 53953]]

creating individually identifiable private information.
    In light of the proposed expansion of the rule to cover certain 
biospecimens regardless of identifiability, this category has been 
modified such that it does not include secondary research use of 
biospecimens. Many of the comments supported the discussion in the 
ANPRM of eliminating the requirement that the information be 
``existing'' at the time the study was suggested for exemption. Thus, 
in addition to changing this category of activities from being exempted 
to being excluded, the proposed exclusion does not require that the 
data exist as of the time that the study commences, but rather is 
expanded to include the secondary research use of data collected in the 
future for research or non-research purposes. The underlying logic 
behind the exclusion in proposed Sec.  __.101(b)(2)(ii) is that such 
research involves no direct interaction or intervention with human 
subjects, and any research use of the information does not impose any 
additional personal or informational risk to the subjects, because (1) 
the information is already available to the public, and so any risk it 
may include exists already, or (2) the information recorded by the 
investigator cannot be identified, and no connection to or involvement 
of the subjects is contemplated. Any requirements of the Common Rule 
would not provide additional protections to subjects, and could add 
substantial administrative burden on IRBs, institutions, and 
investigators. Creating this excluded category avoids that problem.
(4) Questions for Public Comment
    16. Public comment is sought regarding whether it is reasonable to 
rely on investigators to make self-determinations for the types of 
research activities covered in this particular exclusion category. If 
so, should documentation of any kind be generated and retained?
    17. Public comment is requested on the extent to which covering any 
of these activities under the Common Rule would substantially add to 
the protections provided to human research subjects. Is there a way in 
which this exclusion should be narrowed? Public comment is also sought 
regarding whether activities described here should appear as an 
exclusion or as an exemption.
v. Research Conducted by a Government Agency using Government-Generated 
or Government-Collected Data (NPRM at Sec.  __.101(b)(2)(iii))
(1) NPRM Proposal
    The third category of low-risk research activities excluded from 
the proposed rule at Sec.  __.101(b)(2)(iii) is research conducted by a 
federal department or agency using government-generated or government-
collected information obtained for non-research purposes (including 
criminal history data), if the information originally involved a 
collection of information subject to the Paperwork Reduction Act of 
1995, 44 U.S.C. 3501 et seq., the information is maintained on 
information technology that is subject to and in compliance with 
section 208(b) of the E-Government Act of 2002, 44 U.S.C. 3501 note, 
and all of the information collected, used, or generated as part of the 
research is maintained in a system or systems of records subject to the 
Privacy Act of 1974, 5 U.S.C. 552a. This proposed exclusion is 
consistent with the Federal Government's emphasis on minimizing the 
burden on the public and maximizing the value of the information 
collected by the Federal Government, while protecting participant 
privacy and data security.\47\ This exclusion is proposed for 
situations in which both the original data collection and the 
subsequent (secondary) analysis are subject to data security, 
participant privacy, and notice requirements associated with the named 
federal statutes and regulations. As such, it does not seem that the 
delay imposed by obtaining a determination as ``exempt'' or 
``expedited'' is likely to increase the protections provided to those 
who have already provided the government with information for other 
purposes. Public comment is requested on the extent to which covering 
any these activities under the Common Rule would substantially add to 
the protections provided to human research subjects.
---------------------------------------------------------------------------

    \47\ United States Office of Management and Budget, February 14, 
2014, Memorandum to Heads of Executive Departments and Agencies; 
Guidance for Providing and Using Administrative Data for Statistical 
Purposes https://www.whitehouse.gov/sites/default/files/omb/memoranda/2014/m-14-06.pdf. This guidance builds on three previously 
issued OMB memoranda designed to increase the value of existing 
data: Sharing Data While Protecting Privacy (M-11-02 of November 3, 
2010), Open Data Policy-Managing Information as an Asset (M-13-13 of 
May 9, 2013), and Next Steps in the Evidence and Innovation Agenda 
(M-13-17 of July 26, 2013).
---------------------------------------------------------------------------

(2) Questions for Public Comment
    18. Public comment is sought on whether this or a separate 
exclusion should also include research involving information collected 
for non-research purposes by non-federal entities where there are 
comparable privacy safeguards established by state laws and 
regulations, or whether such non-federally conducted research would be 
covered by the proposed exemption at Sec.  __.104(e)(2).
    19. Public comment is requested on the extent to which covering any 
of these activities under the Common Rule would substantially add to 
the protections provided to human research subjects.
    20. Public comment is sought regarding whether it is reasonable to 
rely on investigators to make self-determinations for the types of 
research activities covered in this particular exclusion category. If 
so, should documentation of any kind be generated and retained?
    21. Public comment is sought regarding whether some or all of these 
activities should be exemptions rather than exclusions.
vi. Certain Activities Covered by HIPAA (NPRM at Sec.  
__.101(b)(2)(iv))
(1) ANPRM Discussion
    The public was asked to comment on whether it might be useful to 
adopt the distinction made by the HIPAA Privacy Rule, which 
distinguishes between ``health care operations'' and ``research'' 
activities, defining ``health care operations'' to include, among other 
activities, ``conducting quality assessment and improvement activities, 
including outcomes evaluation and development of clinical guidelines, 
provided that the obtaining of generalizable knowledge is not the 
primary purpose of any studies resulting from such activities.'' The 
public was asked to comment about this specifically in the context of 
quality improvement activities.
(2) NPRM Proposal
    The fourth category of low-risk research activities excluded from 
the proposed rule, found at Sec.  __.101(b)(2)(iv), covers activities 
that are regulated under the HIPAA Privacy Rule (i.e., covered 
entities). These are activities whose risks relate only to privacy and 
confidentiality, and are already subject to independent controls 
provided by HIPAA. Specifically, it is proposed that research, as it is 
defined in this proposed rule, that involves the use of protected 
health information by a HIPAA covered entity for ``health care 
operations,'' ``public health activities,'' or ``research,'' as those 
three terms are defined under the HIPAA Rules, would

[[Page 53954]]

be excluded from the Common Rule. This proposed exclusion would not 
apply if the investigator that receives and uses individually 
identifiable health information for a research study was not covered by 
the HIPAA Rules, even if the entity disclosing the individually 
identifiable health information to the investigator was covered by the 
HIPAA Rules. The exclusion is limited in this way to ensure that it 
only applies to research studies and information that are already 
subject to independent privacy, confidentiality, and security 
protections.
    A majority of comments on the 2011 ANPRM favored distinguishing 
between research and health care operations, as such terms are defined 
in the HIPAA Privacy Rule and the Health Information Technology for 
Economic and Clinical Health (HITECH) Act, and excluding the latter 
from the policy. Some commenters noted that people involved in these 
various activities are protected in other ways, and alluded to the 
sorts of measures that provide protection. Others suggested that any 
exclusions should be limited to data collection and analysis 
activities, or to activities below a certain threshold of risk (i.e., 
minimal risk). A minority of comments objected to these exclusions, 
arguing that these activities represent encroachments on their 
individual rights and privacy, and that oversight in accordance with 
the Common Rule requirements would be more protective. The proposed 
exclusion excludes only certain activities that involve data collection 
and analysis, where privacy safeguards are in place.
(3) Questions for Public Comment
    22. Public comment is requested on whether the protections provided 
by the HIPAA Rules for identifiable health information used for health 
care operations, public health activities, and research activities are 
sufficient to protect human subjects involved in such activities, and 
whether the current process of seeking IRB approval meaningfully adds 
to the protection of human subjects involved in such research studies.
    23. Public comment is sought regarding to what extent the HIPAA 
Rules and HITECH adequately address the beneficence, autonomy, and 
justice aspects for the collection of new information (versus 
information collected or generated in the course of clinical practice, 
e.g., examination, treatment, and prevention). Should this exclusion be 
limited to data collected or generated in the course of clinical 
practice? If additional data collection is allowable, should it be 
limited to what is on the proposed Secretary's list of minimal risk 
activities (discussed in more detail below in II.F.2 of this preamble)?
    24. Public comment is requested on whether additional or fewer 
activities regulated under the HIPAA Privacy Rule should be included in 
this exclusion.
c. Applicability of Exclusions to the Subparts
i. Current Rule
    The current Common Rule does not contain exclusion categories, 
though as discussed above, some of the proposed exclusions are similar 
to activities that are exempt under the current regulations, which 
therefore might provide a basis for comparison.
    All of the current exemption categories can be applied to research 
that is subject to subpart B. None of the current exemption categories 
can be applied to research that is subject to subpart C.
    The exemptions in the current Rule generally apply to subpart D. 
However, the exemption at Sec.  __.101(b)(2), for research involving 
educational tests, survey or interview procedures, or observation of 
public behavior does not apply to subpart D except for research 
involving educational tests or observations of public behavior when the 
investigators do not participate in the activities being observed.
ii. NPRM Proposals
    Language specifying the application of the exclusions to the 
subparts can be found in the NPRM at Sec.  __.101(b)(2) and (3).
    It is proposed that all of the exclusion categories in Sec.  
__.101(b)(2) and (3) apply to research that is subject to subpart B, 
and therefore the requirements imposed by subpart B would not need to 
be met.
    It is similarly proposed that all of the exclusion categories in 
Sec.  __.101(b)(2) and (3) apply to research involving prisoners, 
therefore the requirements of subpart C would not need to be met. This 
would narrow the scope of research currently requiring subpart C review 
and certification to OHRP. Considerations in favor of this conclusion 
include the preponderance of low-risk socio-behavioral research 
designed to improve prisoner welfare, including studies that focus on 
substance abuse treatment, community reintegration, and services 
utilization; the occurrence of prisoner-subjects in research not 
targeting prisoner populations; the occurrence of prisoner-subjects in 
databases or registries; and the broad regulatory interpretation of the 
subpart C ``prisoner'' definition. Public comment is requested on 
whether the application of these exclusions to research involving 
prisoners is appropriate and acceptable.
    It is proposed that all of the exclusion categories in Sec.  
__.101(b)(2) apply to research subject to subpart D, with the exception 
that the exclusion proposed under Sec.  __.101(b)(2)(i) would only 
apply to research involving educational tests or observations of public 
behavior when the investigator does not participate in the activities 
being observed. This limitation would maintain the protection currently 
provided by the similar application of the current exemption Sec.  
__.101(b)(2) to research involving children, and would continue to 
require IRB review under the Common Rule and additional IRB review 
under subpart D of 45 CFR part 46 when the research involves surveys or 
interview procedures with children or observation of public behavior 
when the investigator participates in the activities being observed.
iii. Questions for Public Comment
    25. Should research involving prisoners be allowed to use any or 
all of the exclusions found at Sec.  __.101(b)(2) and (3), as currently 
proposed?
    26. Are there certain provisions within the broader categories 
proposed at Sec.  __.101(b)(2) and (3) to which the subparts should or 
should not apply?
3. Proposed Exemptions (NPRM at Sec.  __.104)
    The Common Rule has been criticized for inadequately calibrating 
the review process to the risk of research. Some have argued that, 
particularly given the paucity of information suggesting significant 
risks to subjects in certain types of survey and interview-based 
research, the current system overregulates such research. Further, many 
critics see little evidence that most IRB review of social and 
behavioral research effectively protects subjects from psychological or 
informational risks. Overregulating social and behavioral research in 
general may serve to distract attention from identification of social 
and behavioral research studies that do pose ethical challenges and 
thus merit significant oversight.
    The proposed exemption categories and attendant policies and 
procedures related to exemptions appear in the NPRM at Sec.  __.104, 
and are guided by the following policy goals:

[[Page 53955]]

     To create procedural efficiencies for IRBs, administrators 
and investigators in making and receiving exemption determinations, 
thereby reducing the overall IRB workload and the wait time for 
investigators to begin their work.
     To ensure that reasonable safeguards are in place for 
certain lower risk research activities not fully excluded under the 
current Common Rule by requiring that research in certain exemption 
categories follow elements of the proposed rule, but not be required to 
undergo full IRB review according to the full set of criteria at Sec.  
__.111(a)(1)-(8) and other regulatory requirements of the Common Rule .
    Note that all of the exemption categories in the current Rule have 
been carried over to the proposed Rule in one or another form. In 
particular, some of the current Rule's exemptions have now become 
exclusions under the NPRM (and thus subject to no administrative or IRB 
review), while some remain in the NPRM's exempt categories section.
    Under the current Common Rule, research may qualify for exemption 
from the regulatory policy if it falls into one of the six current 
categories at Sec.  __.101(b)(1)-(6). Such studies are fully exempt 
from the regulations. The current regulations do not specify who at an 
institution may determine that research is exempt under Sec.  
__.101(b). However, in the past OHRP has recommended that because of 
the potential for conflict of interest, investigators not be given the 
authority to make an independent determination that human subjects 
research is exempt. OHRP has recommended that institutions should 
implement exemption policies that most effectively address the local 
setting and programs of research. OHRP has recognized that this may 
result in a variety of configurations of exemption authority, any of 
which are acceptable assuming compliance with applicable regulations.
    The NPRM proposes to retain the term ``exempt,'' (rather than 
``excused,'' as suggested in the ANPRM) but require that exempt 
research comply with certain provisions of the proposed rule such as 
proposed privacy safeguards at Sec.  __.105 (discussed below). This 
policy retains and, in important respects (through a new safe harbor 
provision), expands the current flexibility of institutions to develop 
a system in which someone at the institution--including the 
investigator, unless prohibited by law--uses an exemption decision tool 
to make the exemption determination.
    It is important to recognize that while in some cases there are new 
requirements that have been imposed on the exemption categories that do 
not exist in the current version of the exemption categories, this 
usually does not actually represent a tightening of the rules for those 
exemptions. To the contrary, these changes are generally being made to 
allow the exemption in question to be expanded to cover activities that 
are not currently exempt. For example, adherence to new privacy 
standards is a new requirement in order for certain surveys to be 
exempt, but these are surveys that under the current Common Rule would 
require IRB review.
    The proposed eight exemptions are divided into three groupings 
according to the kind of risk characteristically involved and what 
protections are called for: (1) Low-risk interventions that do not 
require application of standards for information and biospecimen 
protection; (2) research that may involve sensitive information that 
requires application of standards for information and biospecimen 
protection described in proposed Sec.  __.105; and (3) secondary 
research involving biospecimens and identifiable private information 
that requires application of privacy safeguards discussed at proposed 
Sec.  __.105, broad consent as discussed in proposed Sec.  __.116(c), 
and limited IRB review as discussed in proposed Sec.  __.111(a)(9).
a. Making Exempt Research Determinations (NPRM at Sec.  __.104(c))
i. NPRM Goal
    The goal of this NPRM proposal is to create procedures for 
appropriate exemption determinations in a manner that does not waste 
time and effort.
ii. Current Rule
    In developing policies and procedures addressing the exemptions, 
OHRP currently recommends that when an exemption determination is made, 
the specific exemption category or categories should be included in the 
record of the material supplied to the IRB and this information should 
be available for oversight purposes. In addition, OHRP guidance has 
said that institutional policies and procedures should identify clearly 
who is responsible for making exemption decisions. OHRP notes that 
under current policy a Common Rule Department or Agency retains final 
authority as to whether a particular human subjects research study 
conducted or supported by that Department or Agency is exempt from the 
Common Rule (Sec.  __.101(c)) and that authority continues under the 
proposed regulations.
iii. ANPRM Discussion
    The ANPRM discussed a mechanism to (1) register exempt research, 
and (2) audit a small but appropriate portion of such research, which 
would still be subject to other regulatory protections such as the 
suggested data security and information protection standards and 
certain consent requirements.
    The ANPRM discussed a tracking mechanism to enable institutions to 
assure that such research meets the criteria for inclusion in the 
suggested ``excused'' categories. The original recommendations would 
require investigators to register their study with an institutional 
office by completing a brief form, thus eliminating the current 
practice of not allowing investigators to begin conducting such studies 
until a reviewer had determined it meets the criteria for excused 
research. This would make the institution aware of key information 
about the research (such as the purpose of the research and the name of 
the study's principal investigator), without also requiring that the 
activity undergo a review that, if not done in a timely manner, could 
slow the research without adding any significant protection to 
subjects. In addition, the institution could choose to review some of 
the submissions at the time they are filed and, if deemed appropriate, 
require that the study be sent for expedited review or, in rare cases, 
convened IRB review. It would be made clear that the regulations would 
not require, and in fact, would discourage, having each of these 
registration forms undergo a comprehensive administrative or IRB review 
prior to commencing the study or even afterward.
    The auditing requirement was intended to encourage institutions to 
use the regulatory flexibility suggested for the exempt categories of 
research. The auditing requirement would have provided institutions 
with information needed to assess their compliance with the new 
``excused'' categories without unnecessarily subjecting all such 
research to either prospective review, or even routine review sometime 
after the study is begun. Note that currently, OHRP recommends that 
there be some type of review by someone other than the investigator to 
confirm that a study qualifies as exempt, and many institutions do 
impose such a requirement even though such a requirement is extra-
regulatory.\48\
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    \48\ Office for Human Research Protections. (2011, January 20). 
Exempt Research Determination FAQs. Retrieved from Frequently Asked 
Questions About Human Research: http://www.hhs.gov/ohrp/policy/faq/index.html.

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[[Page 53956]]

    The ANPRM also asked whether it was acceptable for investigators to 
independently determine whether their research was exempt, whether 
review of all registrations should be required, and whether there 
should be a time limitation or waiting period before excused research 
could begin.
    The ANPRM also asked whether it was appropriate to require 
institutions holding a Federalwide assurance (FWA) to conduct 
retrospective audits of a percentage of the excused studies to make 
sure they qualify for inclusion in an excused category, and if so, how 
such audits should be conducted.
iv. NPRM Proposal
    The NPRM proposes to adopt an exemption determination documentation 
requirement which is somewhat different from the registration system 
suggested in the 2011 ANPRM. To assist investigators and institutions 
in making a timely and accurate determination of exemption status the 
NPRM at Sec.  __.104(c) states that federal departments or agencies 
will develop one or more exemption determination tools. Federal 
departments or agencies may create their own tool, or rely on a tool 
created by another department or agency (including the web-based tool 
created by HHS). The tool, which has not yet been developed, will be 
designed in such a way that if the person using the tool inputs 
accurate information about the study, the tool will produce an outcome 
which is the determination as to whether the study is exempt or not. 
Institutions may rely on use of the federally developed tool by 
investigators as a ``safe harbor'' for this determination: So long as 
the information that was provided to the tool was accurate, result of 
the application of the tool will be presumed by the federal departments 
or agencies to be an appropriate determination of exempt status. Use of 
the tool will be voluntary; each institution and agency would determine 
whether to rely on the decision tool for their determinations, and if 
so, who would be allowed to operate it. Institutions, if they so 
choose, could continue to have such determinations made by an 
individual who is knowledgeable about the exemption categories and who 
has access to sufficient information to make an informed and reasonable 
determination. In general, it is expected that investigators would not 
be allowed to make exemption determinations for themselves without the 
use of the decision tool, due to considerations of a conflict of 
interest. It should also be noted that for FDA-regulated device studies 
IRB review is required by statute.
    The NPRM also proposes that the institution or IRB be required to 
maintain records of exemption determinations, which records must 
include, at a minimum, the name of the research study, the name of the 
investigator, and the exemption category applied to the research study. 
Maintenance of the output of the completed decision tool would fulfill 
this recordkeeping requirement.
    In general, commenters to the 2011 ANPRM were not necessarily 
opposed to the concept of registration but sought further information 
on what this process would entail. Public commenters also expressed 
concerns about allowing an investigator to independently make the 
determination that his or her research is exempt. Other commenters 
suggested that this practice would be acceptable for some 
investigators, whose research is well known to IRB members, and is 
clearly within an exempt category. The ANPRM noted concerns that some 
exempt research was unnecessarily delayed by requirements of some 
institutions to review the research to make an exemption decision.
    Several institutions reported that they already as a matter of 
policy require investigators to submit exempt studies to the IRB, not 
necessarily for full board review, but to ensure that the exempt 
determination is valid. These decisions typically are made by the IRB 
administrator and never involve full review unless there is concern 
about the exemption status. Thus, they felt the registration 
requirement was unnecessary and would add new administrative burdens 
for research already considered low-risk.
    Other commenters, such as investigators conducting research 
currently considered exempt, were strongly opposed to a registration 
requirement because it would add a new burden to conducting less than 
minimal risk and exempt research. In addition, commenters raised 
concerns about the administrative burden and need for a retrospective 
audit system of registered research.
    This NPRM proposal is anticipated to provide more flexibility than 
the registration requirement originally proposed, while helping to 
ensure that correct determinations of exempt status are made. The 
existence of a ``safe harbor'' mechanism will hopefully encourage 
institutions to create policies that allow investigators to use the 
tool, and thus to be able to more quickly commence their research 
without needing additional administrative or IRB reviews for these 
types of studies. Other people at the institution who have access to 
accurate information about a proposed study may also utilize the tool, 
which will also allow research to go forward unimpeded.
    In addition, it is proposed that a change to Sec.  __.109(a) be 
made to clarify that the Common Rule does not give IRBs the authority 
to review or approve, require modification in or disapprove research 
that qualifies for exemption under Sec.  __.104(d), (e), or (f)(2).
    There is no auditing requirement in this NPRM proposal. 
Consequently, it does not address concerns raised at the ANPRM stage 
regarding potential conflict of interest if the investigator is 
providing the information to operate the decision tool. Public comment 
is sought on this idea regarding the operational details for further 
development of this proposal. Depending upon the comments received on 
this proposal, additional operational details regarding the proposed 
federally sponsored decision tool would be developed and subject to 
public comment. It should also be noted that the lack of an auditing 
requirement would not prohibit an institution from performing post-
approval monitoring of exemption determinations according to the 
institution's standard operating procedure.
v. Questions for Public Comment
    27. Public comment is sought regarding how likely it would be that 
institutions would allow an investigator to independently make an 
exempt determination for his or her own research without additional 
review by an individual who is not involved in the research and 
immersed in human research protection e.g., a member of the IRB Staff.
    28. Public comment is sought regarding whether an investigator 
would be able to contrive his or her responses to the automated 
exemption decision tool in order to receive a desired result i.e., an 
exempt determination, even if it does not accurately reflect the 
research activities.
    29. Public comment is sought on whether it would be more 
appropriate for some of the exempt categories than others to rely on 
the exemption determination produced by the decision tool where 
investigators themselves input the data into the tool, or whether there 
should be further administrative review in such circumstances.
    30. Public comment is sought regarding whether relying on the 
exemption determination produced by the decision tool where 
investigators themselves input the data into the tool

[[Page 53957]]

as proposed would reduce public trust in research.
    31. Public comment is sought regarding how likely it would be that 
institutions would rely on such a decision tool to provide a safe 
harbor for an investigator making a determination that the proposed 
research qualifies for an exemption, or whether developing such a tool 
would not be worthwhile, and whether institutions would be able to 
adequately manage exemption determinations without the use of the 
decision tool.
    32. Public comment is sought regarding what additional information 
should be required to be kept as a record other than the information 
submitted into the decision tool, for example, a study abstract, the 
privacy safeguards to be employed, or any notice or consent document 
that will be provided.
    33. Public comment is sought regarding the value of adding an 
auditing requirement.
b. Exemptions Subject to the Documentation Requirements of Sec.  
__.104(c) and No Other Section of the Proposed Rule
    Four exemptions are proposed that will not be subject to any 
additional requirements apart from the need to keep a record of the 
determination that the study was exempt. Three of these four exemptions 
in proposed Sec.  __.104(d) are versions of exemptions found in the 
current rule. A revised version of exemption category 1 in the current 
Common Rule (research conducted in established or commonly accepted 
educational settings) is found at proposed Sec.  __.104(d)(1) in the 
NPRM. A revised version of the current exemption category 5 (research 
and demonstration projects) is found at proposed Sec.  __.104(d)(2). 
Exemption category 6 in the current Common Rule (taste and food quality 
evaluations) is found in the NPRM at Sec.  __.104(d)(4), and is 
unchanged.
i. Research Conducted in Established or Commonly Accepted Educational 
Settings (NPRM at Sec.  __.104(d)(1); Current Rule at Sec.  
__.101(b)(1))
(1) NPRM Goal
    The goal is to retain an exemption for a considerable portion of 
education research, but to provide for review if the research might 
adversely affect students' opportunity to learn required educational 
content, or the assessment of educators.
(2) Current Rule
    The current exemption category 1 (Sec.  __.101(b)(1) in the current 
Rule) is for research conducted in established or commonly accepted 
educational settings, involving normal educational practices, such as 
(i) research on regular and special education instructional strategies, 
or (ii) research on the effectiveness of or the comparison among 
instructional techniques, curricula, or classroom management methods.
(3) NPRM Proposal
    The first exemption category is for research conducted in 
established or commonly accepted educational settings when it 
specifically involves normal educational practices. This includes most 
research on regular and special education instructional strategies, and 
research on the effectiveness of, or the comparison among, 
instructional techniques, curricula, or classroom management methods, 
so long as the research is not likely to adversely impact students' 
opportunity to learn required educational content in that educational 
setting or the assessment of educators who provide instruction.
    This exemption category is a revised version of the first exemption 
category in the current Common Rule. The rationale for the revision is 
that there are concerns about whether the conduct of some research 
projects of this type might draw sufficient time and attention away 
from the delivery of the regular educational curriculum, and thereby 
have a detrimental effect on student achievement. The current education 
system places a strong emphasis on student performance on tests in core 
curriculum areas such as reading, science, and mathematics, which have 
a significant effect on such things as grade promotion and student 
assignment to different courses, and cumulatively influence student 
attainment and achievement. It could also have a negative effect on 
teachers being evaluated on the basis of student performance. The 
exemption category is designed to not include such research projects. 
Otherwise, the exemption is retained in order to allow for the conduct 
of education research that may contribute to the important public good 
of improving education, consistent with the principle of beneficence.
(4) Questions for Public Comment
    34. Public comment is sought on whether this exemption category 
should only apply to research activities in which notice that the 
information collected will be used for research purposes is given to 
prospective subjects or their legally authorized representatives as a 
regulatory requirement, when not already required under the Privacy Act 
of 1974. If so, comment is sought on what kind of information should be 
included in the notice, such as the research purpose, privacy 
safeguards, contact information, etc. Comment is also sought on how 
such a notice should be delivered, e.g., publication in a newspaper or 
posting in a public place such as the school where the research is 
taking place, or by individual email or postal delivery. Note that 
other requirements, such as those of the Family Educational Rights and 
Privacy Act (FERPA) or the Protection of Pupil Rights Amendment, may 
also apply. Would requiring notice as a condition of this exempt 
research strike a good balance between autonomy and beneficence?
    35. Public comment is sought on whether the privacy safeguards of 
Sec.  __.105 should apply to the research included in Sec.  
__.104(d)(1), given that such research may involve risk of disclosure 
of identifiable private information.
ii. Research and Demonstration Projects Conducted or Supported by a 
Federal Department or Agency (NPRM at Sec.  __.104(d)(2); Current Rule 
at Sec.  __.101(b)(5))
(1) NPRM Goal
    The NPRM exemption proposed at Sec.  __.104(d)(2) is for research 
and demonstration projects involving public benefit or service 
programs, and is a slightly revised version of exemption 5 in the 
current Common Rule.
    The proposed regulatory revision and change in interpretation of 
the exemption is designed to clarify the scope of the exemption so that 
more research studies would be exempt. It is believed that these 
changes would make the exemptions easier to apply. It is also designed 
to allow the Federal Government to carry out important evaluations of 
its public benefit and service programs to ensure that those programs 
are cost effective and deliver social goods, consistent with the 
principle of beneficence.
(2) Current Rule
    The current version of this exemption category was originally 
created based on the recognition that alternative processes are in 
place in which ethical issues raised by research in public benefit or 
service programs are be addressed by the officials who are familiar 
with the programs and responsible for their successful operation under 
state and federal laws. These alternative processes implicitly consider 
risk, but there is not a predefined scope for the likelihood or

[[Page 53958]]

magnitude of risk in these research activities. In fact, the Secretary 
of HHS noted in 1983 that these demonstration and service projects are 
already subject to procedures which provide for extensive review by 
high level officials in various program administration offices. The 
Secretary further noted that review by an IRB would be duplicative and 
burdensome to state and local agencies and to other entities 
participating in demonstration projects. It was thought that removal of 
this unnecessary layer of review would not only reduce the cost of the 
projects but also help avoid unnecessary delays in project 
implementation.\49\
---------------------------------------------------------------------------

    \49\ 48 FR 9266 (Mar. 4, 1983).
---------------------------------------------------------------------------

    OHRP has interpreted the current exemption category 5 (Sec.  
__.101(b)(5) in the current Common Rule) to apply only to those 
research and demonstration projects designed to study a ``public 
benefit or service program'' that a Common Rule department or agency 
itself administers, and for which the public benefit or service program 
exists independent of any research initiative. As an example, OHRP has 
in the past said that a research study to evaluate a Centers for 
Medicare & Medicaid Services (CMS)-administered demonstration project 
comparing two different mechanisms for reimbursing providers under 
Medicare or Medicaid would meet this exemption. However, this exemption 
would not apply to some types of research, for example, the evaluation 
of clinical trials (e.g., a National of Institutes of Health-funded 
clinical trial comparing two treatment regimens for heart disease), 
even if such studies would inform Medicare reimbursement policies.
(3) ANPRM Discussion
    The ANPRM asked several questions about the interpretation and 
applicability of current exemption category 5 (current Common Rule at 
Sec.  __.101(b)(5)), including the scope of the current interpretation 
of the category 5 exemption. The ANPRM also asked if the current 
category 5 guidance entitled, ``OPRR Guidance on 45 CFR 46.101(b)(5),'' 
\50\ should be revised, or if additional guidance on the interpretation 
of exemption category 5 is needed.
---------------------------------------------------------------------------

    \50\ See 48 FR 9266-9270 (Mar 4, 1983). (OPRR Guidance on 45 CFR 
46.101(b)(5), Exemption for Research and Demonstration Projects on 
Public Benefit and Service Programs, http://www.hhs.gov/ohrp/policy/exmpt-pb.html).
---------------------------------------------------------------------------

    More specifically, the ANPRM asked whether this exemption should be 
revised to assure that it is not misinterpreted or misapplied, whether 
broadening it would result in inappropriately increasing risks to 
subjects, how such risks might be mitigated, and whether OHRP guidance 
should be revised.
(4) NPRM Proposal
    The second proposed exemption category (NPRM at Sec.  __.104(d)(2)) 
is for research and demonstration projects that are conducted or 
supported by a Federal department or agency, or otherwise subject to 
the approval of department or agency heads, and that are designed to 
study, evaluate, or otherwise examine public benefit or service 
programs, including procedures for obtaining benefits or services under 
those programs, possible changes in or alternatives to those programs 
or procedures, or possible changes in methods or levels of payment for 
benefits or services under those programs.
    It is proposed that each federal department or agency conducting or 
supporting the research and demonstration projects would be required to 
establish, on a publicly accessible federal Web site or in such other 
manner as the department or agency head may prescribe, a list of the 
research and demonstration projects that the Federal department or 
agency conducts or supports under this provision. The research or 
demonstration project would be required to be published on this list 
prior to or upon commencement of the research. Agencies and departments 
would be able to create or use their own Web sites for this purpose, or 
use a Web site created by OHRP. Note that for studies exempted pursuant 
to Sec.  __.104(d)(2), the recordkeeping requirement at proposed Sec.  
__.104(c) would be deemed to be satisfied by the published list 
required under proposed Sec.  __.104(d)(2)(i).
    There were few responses to the questions posed on this exemption 
in the 2011 ANPRM. However, those that did comment noted that this 
category is often misunderstood by IRBs and, at best, would benefit 
from clearer guidance. Commenters said that examples would help 
investigators and IRBs understand when research activities included in 
demonstration projects constitute human subjects research subject to 
the Common Rule. Commenters noted that many activities in demonstration 
projects do not contribute to generalizable knowledge as they produce 
results that are relevant only to the program being assessed; as such, 
many of these activities do not meet the Common Rule's regulatory 
definition of ``research'' and thus fall outside of the rule. Other 
commenters said that some activities in this category are mandated or 
required by law or regulation and should not be considered to be under 
the purview of the Common Rule. It was noted that the critical issue in 
these studies should be protecting privacy and as long as measures are 
in place to do so, additional protections are not required.
    The revision of the language in this exemption clarifies the 
original language to say that a federally conducted project examining 
any aspect of a public benefit or service program would qualify for the 
exemption. The clauses concerning procedures for obtaining benefits, 
other changes in programs and procedures, and changes in methods or 
levels of payment are merely examples of such projects, and are not 
considered to be all-inclusive.
    In addition, OHRP proposes to clarify its interpretation of public 
benefit and service programs which are being evaluated as part of the 
research to include public benefit or service programs that a Common 
Rule department or agency does not itself administer through its own 
employees or agents, but rather funds (i.e., supports) through a grant 
or contract program. Therefore, the exemption would be clarified to 
apply to research and demonstration projects supported through federal 
grants or cooperative agreements, for example. These activities include 
appropriate privacy, confidentiality and security safeguards for any 
biospecimen and information used in this research. For example, 
information collected in some demonstration projects are subject to the 
protections of the HIPAA rules, and Federal agencies include conditions 
in grants or cooperative agreements which require the recipient to 
protect the confidentiality of all project-related information that 
includes personally identifying information.
    It is believed that these changes would make the exemptions easier 
to apply. It is also designed to allow the Federal Government to carry 
out important evaluations of its public benefit and service programs to 
ensure that those programs are cost effective and deliver social goods. 
The proposed changes to this exemption would require OHRP to revise its 
existing guidance document on this exemption accordingly.
    These changes would bring the language into conformance with other 
provisions of the rule that refer to research ``conducted or 
supported'' by Federal agencies. Both current practice and the edited 
language cover such

[[Page 53959]]

research, whether it is conducted directly by federal staff or through 
a contract, cooperative agreement, or grant. These methods of 
administration are, of course, always subject to department or agency 
head approval, directly or by delegation. In addition, some of these 
research and demonstration projects are conducted through waivers, 
interagency agreements, or other methods that also require agency head 
approval. Accordingly, both the previous and the revised language allow 
for the full panoply of methods by which research and demonstration 
projects on public benefit or service programs can be carried out.
    Although research such as that described above is exempt, an 
additional requirement is proposed. In the interest of transparency, 
each Federal department or agency conducting or supporting the research 
and demonstration projects must establish, on a publicly accessible 
federal Web site or in such other manner as the Secretary may 
prescribe, a list of the research and demonstration projects which the 
federal department or agency conducts or supports under this provision. 
The research or demonstration project must be published on this list 
prior to or upon commencement of the research. The agency determines 
what will be included on this list and maintains its oversight. 
Agencies that already publish research and demonstration projects on a 
publicly accessible Web site could satisfy this proposed requirement if 
the existing Web site were to include a statement indicating which of 
the studies were determined to meet this exemption. The goal of this 
proposed requirement is to promote transparency of federally conducted 
or supported activities affecting the public that are not subject to 
oversight under the Common Rule. It should not create any delay to the 
research. HHS will develop a resource that all Common Rule agencies may 
use to satisfy the requirement at proposed Sec.  __.104(d)(2)(i). 
Alternatively, an agency can make its own Web site.
    Currently, there is no such comprehensive listing of studies that 
have been determined to have met this exemption, so this requirement 
would also enable Common Rule departments and agencies to better assess 
the types of projects that use this exemption, and consider whether any 
changes to its scope would be appropriate.
(5) Questions for Public Comment
    36. Public comment is sought on whether this exemption category 
should only apply to research activities in which notice is given to 
prospective subjects or their legally authorized representatives as a 
regulatory requirement. If so, comment is sought on what kind of 
information should be included in the notice, e.g., the research 
purpose, privacy safeguards, or contact information. Also comment on 
how such a notice should be delivered; e.g., publication in a newspaper 
or posting in a public place, or by individual email or postal 
delivery. Would requiring notice as a condition of this exempt research 
strike a good balance between autonomy and beneficence? In many cases, 
it may be that individual notice or consent to all potentially affected 
persons before the research or demonstration commences is ordinarily 
impossible in the conduct of such studies. For example, if a research 
or demonstration project will affect all inhabitants of a large 
geographic area (e.g., a housing, a police patrol, a traffic control, 
or emergency response experiment), or all clients or employees of a 
particular program or organization or setting will be subject to a new 
procedure being tested (e.g. a new approach to improving student 
performance, a new anti-smoking or anti-obesity program, a new method 
for evaluating employee performance), would it be possible to make 
participation voluntary for all affected individuals, or even to 
identify and inform all affected individuals in advance?
    37. Public comment is sought on whether this exemption category is 
appropriate based on the recognition that alternative processes are in 
place in which ethical issues raised by research in public benefit or 
service programs would be addressed by the officials who are familiar 
with the programs and responsible for their successful operation under 
state and federal laws, rather than meeting specific risk-based 
criteria, or whether risk limitations should be included, and if so, 
what those limitations should be. Though long-standing, this exemption 
has never identified specific risk-based criteria, or risk limitations 
to bound the type of projects that may be covered. When originally 
promulgated, the exemption did stipulate that following the review of 
such projects, if the Secretary determines that the research or 
demonstration project presents a danger to the physical, mental, or 
emotional well-being of a participant or subject, then written informed 
consent would be required. Public comment is sought on whether to limit 
the risk that can be imposed on subjects while using this exemption, 
and if so, how to characterize those limits in a clear fashion. If more 
than minimal risk interventions are included, public comment is sought 
on whether, for transparency, this should be made clear in the 
regulatory text.
    With regard to the issue of risks encountered by participants in 
such research or demonstration projects, comments are also sought 
regarding the argument that any and every demonstration project 
involving changes in public benefit or service programs (e.g., water or 
sewage treatment programs or pollution control programs, programs 
involving educational procedures, or programs involving emergency 
procedures related to extreme weather events, etc.) exposes those 
affected to possible risks of some kind. In this regard, those risks 
are ordinarily and perhaps always no different in kind or magnitude 
than those involved in simply making the change in procedures without 
using research tools to evaluate them. For example, health care 
providers could be required to perform certain sanitation reforms to 
prevent patient infections whether or not such reforms were first 
tested in practice through a research or demonstration project. It is 
common for all Federal departments and agencies that regulate private 
or public organizations to impose conditions of participation in public 
programs providing for safety, program integrity, financial reporting, 
etc. Public comment is sought regarding whether there should be 
conditions (e.g., an individual notice or consent requirement) imposed 
on such research or demonstration projects involving public benefit or 
service programs which might lead to significant impediments or 
limitations on testing and evaluation before or after being imposed 
program-wide. Would the effect of imposing expensive or impracticable 
conditions on public benefits or services evaluations be to reduce the 
number of such evaluations and consequently to expose program 
participants to increased risk through exposure to untested reforms?
    38. Public comment is sought on whether the existing privacy 
safeguards for such activities, including the Privacy Act, HIPAA rules, 
and other federal or state privacy safeguards provide sufficient 
independent controls, or whether other safeguards such as the privacy 
safeguards of Sec.  __.105 should be applied.

[[Page 53960]]

iii. Research involving benign interventions in conjunction with the 
collection of data from an adult subject (NPRM at Sec.  __.104(d)(3))
(1) NPRM Goal
    The goal of this proposed new exemption for studies that involve 
benign interventions is to eliminate IRB review of these low-risk 
studies to reduce time and effort, allow IRBs to focus more attention 
on research with higher risks or presenting other ethical challenges, 
and to enable this research to go forward.
(2) Current Rule
    Currently, research studies in the social and behavioral sciences 
that do not qualify for exemption category 2 (current Common Rule at 
Sec.  __.101(b)(2)), but that involve certain types of well-understood 
interactions with subjects (e.g., asking someone to watch a video and 
then conducting word association tests), require either convened board 
or expedited IRB review.
(3) ANPRM Discussion
    The ANPRM considered whether to include on the list of exempt 
studies certain types of social and behavioral research conducted with 
competent adults that would involve specified types of benign 
interventions commonly used in social and behavioral research, that are 
known to involve virtually no risk to subjects, and for which prior 
review does little to increase protections to subjects. These would be 
methodologies that are familiar to people in everyday life and in which 
verbal or similar responses would constitute the research data being 
collected. The ANPRM asked whether this category should include 
research in which there is deception.
(4) NPRM Proposal
    The proposed exemption at Sec.  __.104(d)(3) is new and includes 
research involving benign interventions in conjunction with the 
collection of data from an adult subject through verbal or written 
responses (including data entry) or video recording if the subject 
prospectively agrees to the intervention and data collection and at 
least one of the following is met:
     The information obtained is recorded in such a manner that 
human subjects cannot be identified directly or through identifiers 
linked to the subjects; or
     Any disclosure of the human subjects' responses outside 
the research would not reasonably place the subjects at risk of 
criminal or civil liability or be damaging to the subjects' financial 
standing, employability, educational advancement, or reputation.
    For the purpose of this proposed provision, benign interventions 
would be brief in duration, harmless, painless, not physically 
invasive, not likely to have a significant adverse lasting impact on 
the subjects, and it would be required that the investigator has no 
reason to think the subjects will find the interventions offensive or 
embarrassing. If these criteria were met, such benign interventions 
might include research activities in which a subject is asked to read 
materials, review pictures or videos, play online games, solve puzzles, 
or perform cognitive tasks. If the research involves deceiving the 
subjects regarding the nature or purposes of the research, this 
exemption would not be applicable unless the subject authorizes the 
deception. For the purpose of this proposed provision, authorized 
deception would be prospective agreement by the subject to participate 
in research where the subject is informed that he or she will be 
unaware of or misled regarding the nature or purposes of the research.
    Many commenters to the 2011 ANPRM supported adding another 
exemption category of research for certain types of social and 
behavioral activities, conducted with competent adults, that would 
involve specified types of benign interventions beyond educational 
tests, surveys, focus groups, interviews, and similar procedures that 
are commonly used in social and behavioral research, that are known to 
involve virtually no risk to subjects, and for which IRB review does 
little to increase protections for subjects. However, many commenters 
were opposed to the requirement that subjects be ``competent adults'' 
in order for the expanded exemption to apply, asking whether tests of 
competency would be required for such research to proceed.
    This new exemption category addresses research involving benign 
interventions, in which information is collected through verbal or 
written responses and recorded in a manner such that human subjects 
cannot be identified, or where the disclosure of responses would not 
place the subjects at risk of criminal or civil liability or be 
damaging to the subjects' financial standing, employability, 
educational advancement, or reputation. Here, a ``benign intervention'' 
is categorized as one that is temporary and painless, producing no 
lasting negative impacts. Examples of benign interventions might 
include research activities in which a subject is asked to read 
materials, review pictures or videos, play online games, solve puzzles, 
or perform cognitive tasks, so long as the interventions meet the 
requirements for this category.
    The NPRM proposes to allow this type of research to occur without 
the requirements of informed consent or data security protections 
because neither the intervention nor the identifiability of the 
information is likely to result in harm to the subject, and the subject 
must prospectively agree to the intervention and the data collection. 
This exemption would include some research using authorized deception, 
where there is a prospective agreement by the research subject to 
participate in the activity after being informed that he or she will be 
unaware or misled regarding the nature of the research (Sec.  
__.104(d)(3)(iii)-(iv)). Subjects must be adults, but the provision 
does not specify that they must be competent, and so tests of 
competency are not necessary; however, the presumption is that in 
keeping with the principle of respect for persons, these subjects will 
not be taken advantage of. This new exemption category is being added 
because respect for persons is accomplished through the prospective 
subject's prospective agreement or authorization, the research 
activities pose little risk to subjects, and the use of this exemption 
for many social or behavioral studies will enable IRBs to devote more 
time and attention to research studies involving greater risks or 
ethical challenges.
(5) Questions for Public Comment
    39. Public comment is sought on whether this exemption category 
should only apply to research activities in which notice is given to 
prospective subjects or their legally authorized representatives as a 
regulatory requirement. If so, comment is sought on what kind of 
information should be included in the notice, such as the research 
purpose (if authorized deception is not utilized), privacy safeguards, 
contact information, etc. Would requiring notice as a condition of this 
exempt research strike a good balance between autonomy and beneficence?
    40. Public comment is sought regarding what improvements could be 
made to the language describing the type of interventions in this 
exemption category so as to make clear what interventions would or 
would not satisfy this exemption category.
    41. Public comment is sought on whether it is reasonable, for 
purposes of this exemption, to rely on the exemption determination 
produced by the decision tool where investigators

[[Page 53961]]

themselves input the data into the tool, or whether there should be 
further administrative review in such circumstances.
iv. Taste and Food Quality Evaluation and Consumer Acceptance Studies 
(NPRM at Sec.  __.104(d)(4); current Rule at Sec.  __.101(b)(6))
    The exemption proposed in Sec.  __.104(d)(4) is found in the 
current Common Rule at Sec.  __.101(b)(6). This exemption is for taste 
and food quality evaluation and consumer acceptance studies if 
wholesome foods without additives are consumed, or if a food is 
consumed that contains a food ingredient at or below the level and for 
a use found to be safe, or agricultural chemical or environmental 
contaminant at or below the level found to be safe, by FDA or approved 
by the EPA or the Food Safety and Inspection Service of the U.S. 
Department of Agriculture.
    This exemption is retained unchanged from the current Common Rule. 
The research activities included under this intervention are relatively 
benign, no sensitive information is collected, and presumably subjects 
are made aware of the nature of the activity before they participate, 
and may exercise their autonomy in choosing whether or not to 
participate. However, since the research activities involve physical 
interventions with the subject, the rules relating to exemption 
determinations and the record-keeping requirement for exempt activities 
are appropriate.
(1) Question for Public Comment
    42. Public comment is sought on whether this exemption category 
should be narrowed to apply only to research activities in which notice 
is given to prospective subjects or their legally authorized 
representatives as a regulatory requirement. If so, comment is sought 
on what kind of information should be included in the notice such as 
the research purpose, privacy safeguards, contact information, etc. 
Would requiring notice as a condition of this exempt research strike a 
good balance between autonomy and beneficence? Should prospective 
subjects be given the explicit opportunity to opt out of such research?
c. Exemptions Subject to the Documentation Requirements of Sec.  
__.104(c) and the Privacy Safeguards Described in Sec.  __.105
    Two exemption categories are proposed which will be subject to the 
documentation requirement and the new privacy safeguards. The first 
exemption category is for certain research involving educational tests, 
surveys, interviews, or observation of public behavior. The second 
category is for secondary research use of identifiable private 
information originally collected for non-research purposes where notice 
was given.
    One of the functions of IRB review when a study presents only 
informational risks is to ensure the sufficiency of the investigator's 
plan for protecting any identifiable private information that will be 
collected, created, or used as part of the study. In keeping with one 
of the goals of this NPRM and as discussed in section II.A.3 of this 
preamble, to reduce burden associated with research that includes 
sufficient protections to research subjects, this NPRM proposes to 
eliminate the need for IRB review for studies involving the collection 
of identifiable private information when collected through educational 
tests (cognitive, diagnostic, aptitude, achievement), survey 
procedures, interview procedures, or observation of public behavior 
(including visual or auditory recording), or in studies involving only 
the secondary analysis of identifiable private information originally 
collected for non-research purposes when the proposed privacy 
safeguards at Sec.  __.105 are met. The newly proposed Sec.  __.105 
offers three avenues to meeting the data security and privacy 
protection requirements, all three of which are posited to be at least 
as protective as those usually that result from IRB review.
     The investigator is required by law to comply with, or 
voluntarily complies with, the HIPAA Rules;
     The activity is conducted by federal departments and 
agencies, and the activity is or will be maintained on information 
technology that is subject to and in compliance with section 208(b) of 
the E-Government Act of 2002, 44 U.S.C. 3501 note, if all of the 
information collected, used, or generated as part of the activity will 
be maintained in systems of records subject to the Privacy Act of 1974, 
5 U.S.C. 552a, and the research will involve a collection of 
information subject to the Paperwork Reduction Act of 1995, 44 U.S.C. 
3501 et seq.; or
     The investigator complies with the privacy safeguards 
promulgated by the Secretary of HHS (which standards will be designed 
so that they could be readily implemented by an individual 
investigator, and would involve minimal cost and effort to implement).
    It is believed that the protections afforded by the Paperwork 
Reduction Act, section 208 of the E-Government Act, and the Privacy Act 
in combination with each other are generally equivalent to the privacy 
protections that result from IRB review. It is similarly believed that 
the privacy protections afforded by HIPAA in the context of the studies 
exempted under Sec.  __.104(e) justify eliminating IRB review.
    The proposed section 105 also includes limitations on the use, 
release, and disclosure of the identifiable private information 
collected or maintained for research subject to this Rule.
    Although most if not all of these requirements are already in 
effect for federal entities and HIPAA covered entities, they will 
likely be new to some institutions and their investigators. The intent 
is that Secretary would develop a list of ``reasonable and appropriate 
safeguards'' that would be easily implemented by investigators. As 
such, it is envisioned that the Secretary's privacy safeguards 
described in proposed Sec.  __.105 would be designed as a checklist 
that could be easily monitored by investigators and IRB members alike. 
In the case where IRB members have additional expertise, they may 
choose to deviate from the Secretary's list. Acknowledging that it is 
difficult for the public to fully comment on the implications of such a 
checklist before it has been developed; the Rule includes a requirement 
that the Secretary solicit public comment on the proposed minimum 
safeguards.
i. Questions for Public Comment
    43. Public comment is sought on the concept of requiring such 
minimum safeguards and limitations on disclosure, as well as whether 
the requirements of the proposed Sec.  __.105 would constitute a 
broadening of IRB responsibilities rather than a streamlining of the 
implementation of responsibilities that many IRBs already adopted. If 
an institution does view this as an inordinate broadening of 
responsibilities, does the institution currently have in place 
alternative mechanisms for ensuring data security and participant 
privacy in a research context? Suggestions for alternative approaches 
to meeting public expectation that federally sponsored research 
safeguard their data and protect privacy are sought during this public 
comment period.
    44. Public comment is sought regarding whether the proposed Rule's 
information security requirements for biological specimens and 
identifiable private information are highly technical and require a 
level of expertise not currently available to most IRBs. Do these 
security requirements unrealistically expand IRB responsibilities 
beyond current competencies?

[[Page 53962]]

ii. Research Involving Educational Tests, Surveys, Interviews, or 
Observation of Public Behavior if the Information is Recorded with 
Identifiers and even if the Information is Sensitive (NPRM at Sec.  
__.104(e)(1))
(1) NPRM Goals
    The goal of the proposed exemption at Sec.  __.104(e)(1) is to 
eliminate the need for IRB review of certain low-risk studies that 
involve collecting information by means of educational tests, surveys, 
interviews, or observation of public behavior. The intent is that this 
change would reduce IRB and investigator time and effort in reviewing 
and submitting protocols, and would allow IRBs to focus more attention 
on research with higher risks or presenting other ethical challenges, 
would respect autonomy, and would enable this research to go forward.
(2) Current Rule
    The current Common Rule only allows these activities, involving the 
recording of identifiable information about research subjects, to be 
exempt if the disclosure of the identifiable information outside the 
research could not reasonably place the subjects at risk of criminal or 
civil liability or be damaging to the subjects' financial standing, 
employability, or reputation.
(3) ANPRM Discussion
    The ANPRM discussed criticisms of the current Common Rule that it 
does not adequately calibrate the review process to the level of risk 
of the research, particularly in social and behavioral research. It 
also discussed whether answering questions should be sufficient 
indication of willingness to participate in survey or interview 
research. It distinguished between informational or psychological risks 
and physical risks, and raised questions about how effectively IRB 
review provides protections from informational or psychological risks.
    Specifically, the ANPRM discussed expanding the current exemption 
category 2 (current Rule at Sec.  __.101(b)(2)) to include all studies 
involving educational tests, surveys, interviews, and similar 
procedures, so long as the subjects are competent adults, without any 
further qualifications (but subject to the data security and 
information protection standards).
(4) NPRM Proposal
    The exemption proposed in Sec.  __.104(e)(1) covers research, not 
including interventions, involving the use of educational tests 
(cognitive, diagnostic, aptitude, achievement), survey procedures, 
interview procedures or observation of public behavior (including 
visual or auditory recording), if the information obtained is recorded 
in such a manner that human subjects can be identified directly or 
through identifiers linked to the subjects. The research in this 
category is exempt from most requirements of the NPRM, but 
investigators must adhere to the privacy safeguards outlined in 
proposed Sec.  __.105. Note that the language used in this exemption is 
very similar to that used in the current exemption 2, proposed 
exclusion Sec.  __.101(b)(2)(i), and the proposed exemption at Sec.  
__.104(d)(3); unlike the language in those three places, however, the 
proposed exemption at Sec.  __.104(e)(1) would allow for research to be 
exempt where sensitive identifiable private information is collected 
the release of which could pose some measure of risk. However, the 
exemption is subject to adherence to the proposed Sec.  __.105 privacy 
safeguards, which are designed to limit the chances that the release of 
that information would lead to harm. This exemption category includes 
research involving test development, and use of tests that have not 
already been shown to be valid or reliable, inasmuch as such research 
activity is desirable in order to determine the their validity and 
reliability, and the exemption category provides safeguards to ensure 
that results will not be used to evaluate student achievement. Note 
that the activities that are currently exempted under exemption 
category 2 (involving similar ways to collect information, but only 
where either the identity of the subject is not recorded or disclosure 
of the information would not have any adverse consequences to the 
subject) would be moved under the NPRM to the proposed exclusion at 
Sec.  __.101(b)(2)(i), rather than being under an exemption. That 
proposed exclusion is discussed in section II.A.2 of this preamble. 
Note also that this proposed exemption would cover the research 
activities under the exemption in the current Rule at Sec.  
__.101(b)(3)(ii), such as the research activities funded subject to the 
Department of Justice statute related to certificates of 
confidentiality (42 U.S.C. 3789g) and the information collections 
subject to the confidentiality provisions of the Education Sciences 
Reform Act (20 U.S.C. 9573) of the Department of Education. Presumably 
the safeguards provided by these statutes satisfy the privacy 
safeguards of the proposed Sec.  __.105.
    Consistent with the spirit of the principle of respect for persons, 
investigators should provide prospective subjects with sufficient 
information to make an informed decision about participation. Public 
comment is sought regarding whether some kind of notice must be given 
as a regulatory requirement for this exemption, and if so, what kind of 
information must be included in that notice.
    The rationale for characterizing these activities as low-risk is 
that prospective subjects can decline to participate or answer specific 
questions in procedures they are already familiar with from the 
experiences of daily life, and, importantly, that the information will 
be protected through the new privacy safeguards of Sec.  __.105. The 
availability of this exemption is designed to reduce the volume of 
information collection that IRBs process, thereby enabling them to 
devote more time and attention to research studies which pose greater 
risks or involve ethical challenges.
    The underlying assumptions and rationale for this exemption mirror 
the rationale for the exclusion proposed in Sec.  __.101(b)(2)(i)(C). 
Here again it is presumed that the subjects are sufficiently familiar 
with survey and interview procedures and educational tests to be able 
to knowingly and willingly provide the information, or decline to 
participate. The rationale for this exemption category is that 
prospective subjects can decline to participate or answer specific 
questions in procedures they are already familiar with from the 
experiences of daily life, and that the information collected will be 
protected through the privacy safeguards of Sec.  __.105.
    However, there are situations in which these assumptions would not 
always hold. For instance, administration of a questionnaire or 
participation in a focus group on a sensitive topic may induce 
significant stress in some individuals, or individuals approached about 
taking a survey may feel compelled to participate. Whether and how this 
exemption should be bounded so that the final rule archives a balance 
among the principles of beneficence, autonomy, and justice is the 
subject of a request for public comment on this proposed exemption. The 
use of this exemption is designed to enable IRBs to devote more time 
and attention to research studies which pose greater risks or involve 
more challenging ethical concerns.

[[Page 53963]]

(5) Questions for Public Comment
    45. Public comment is sought on whether the proposed exemption 
regarding the use of educational tests, survey procedures, interview 
procedures, or observation of public behavior (Sec.  __.104(e)(1)) 
should be applied to research involving the use of educational tests 
with children and whether it should also be applied to research 
involving the use of survey or interview procedures with children. If 
so, for research involving children, should the permissible survey or 
interview topics be limited in some way?
    46. Public comment is sought on whether this exemption category 
should only apply to research activities in which notice is given to 
prospective subjects or their legally authorized representatives as a 
regulatory requirement. If so, comment is sought on what kind of 
information should be included in the notice such as the research 
purpose, privacy safeguards, contact information, etc. Would requiring 
notice as a condition of this exempt research strike a good balance 
between autonomy and beneficence? Should prospective subjects be given 
the explicit opportunity to opt out of such research?
    47. Public comment is sought on whether it is reasonable, for 
purposes of this exemption, to rely on the exemption determinations 
produced by the decision tool where investigators themselves input the 
data into the tool, or whether there should be further administrative 
review in such circumstances?
    48. Public comment is sought on whether this exemption category 
should be narrowed such that studies with the potential for 
psychological risk are not included. Are there certain topic areas of 
sensitive information that should not be covered by this exemption? If 
so, please provide exemplary language to characterize such topic areas 
in a manner that would provide clarity for implementing the Rule.
iii. Secondary Research Use of Identifiable Private Information (NPRM 
at Sec.  __.104(e)(2))
(1) NPRM Goal
    The goal of the proposed new exemption category at Sec.  
__.104(e)(2) is to facilitate secondary research using identifiable 
private information that has been or will be collected or generated for 
non-research purposes, when prior notice has been given and privacy 
safeguards and prohibitions on re-use of the information are in place. 
Technological developments and the creation of large databases have 
significantly increased the potential benefits of secondary research 
analyses. The proposed exemption category would eliminate the need for 
IRB review of certain low-risk studies that only involve secondary use 
of identifiable private information that was collected for non-research 
purposes. The information would be protected under the privacy 
safeguards of Sec.  __.105, and respect for persons would be 
demonstrated through a requirement for notice. The proposed exemption 
is limited to the research use of the identifiable private information 
for the purposes of the specific research for which the investigator or 
recipient entity requested access to the information, not for any 
further secondary research use. This proposed exemption is intended to 
reduce IRB and investigator time and effort, and allow IRBs to focus 
more attention on research with higher risks or presenting other 
ethical challenges. The exemption would enable beneficial secondary 
research to occur without being impeded by administrative or IRB 
review, but with privacy safeguards to avoid harm and a notice 
requirement to show respect for persons. Public comment is sought 
regarding this proposal, including what limits in scope it should have, 
what controls and protections should be attached above and beyond the 
privacy safeguards of Sec.  __.105, and how best to respect the 
autonomy or other interests of the individuals who are the subjects of 
the information.
(2) Current Rule
    Under the current Common Rule, secondary research studies using 
identifiable private information undergo IRB review and approval, often 
using the expedited review procedure. If the activity satisfies the 
relevant criteria, the IRB may waive the requirement for informed 
consent, which IRBs typically do.
(3) ANPRM Discussion
    The ANPRM proposed that with regard to an investigator's use of 
pre-existing data (i.e., data that were previously collected for 
purposes other than the currently proposed research study) originally 
collected for non-research purposes, then, as is currently the rule, 
written consent or waiver of consent would only be required if the 
investigator obtains information that identifies the subjects. Under 
the ANPRM, there would accordingly have been no change in the current 
ability of investigators to conduct such research using de-identified 
data or a limited data set, as such terms are used in the HIPAA Rules, 
without obtaining consent.
    Second, the ANPRM proposed that if the data were originally 
collected for research purposes, then consent would be required 
regardless of whether the investigator obtains identifiers. This would 
have been a change with regard to the current interpretation of the 
Common Rule in the case where the investigator does not obtain any 
identifiers. That is, the allowable current practice of telling the 
subjects, during the initial research consent, that the information 
they are providing will be used for one purpose, and then after 
stripping identifiers, allowing it to be used for a new purpose to 
which the subjects never consented, would not have been allowed.
(4) NPRM Proposal
    The NPRM proposal here is for a new exemption covering the 
secondary research use of identifiable private information that has 
been or will be acquired for non-research purposes, if the following 
are met:
     Prior notice has been given to the individuals to whom the 
identifiable private information pertains that such information may be 
used in research;
     The privacy safeguards of Sec.  __.105 are required; and
     The identifiable private information is used only for 
purposes of the specific research for which the investigator or 
recipient entity requested access to the information.
    Under the current system, IRBs frequently waive consent for 
research involving the secondary use of identifiable private 
information, particularly when the data sets are large or drawn from 
multiple institutions. In such circumstances, IRBs often impose privacy 
and data security protection requirements. However, since this proposed 
exemption category requires that the privacy safeguards at Sec.  __.105 
are in place, requiring these studies to undergo IRB review will 
provide little or no additional protections to subjects, while 
continuing to generate potentially substantial burdens on investigators 
and IRBs and diverting IRB resources away from research that may 
involve more serious ethical challenges.
    Under this proposed exemption there will be greater protections for 
these research subjects than is currently the case. The new privacy 
safeguards of Sec.  __.105 would be applied to this research, and would 
be the same safeguards that would be used for many other types of 
research under the NPRM. In addition, the scope of the exemption is 
limited to the specific research for

[[Page 53964]]

which the investigator or recipient entity requested access to the 
information, so the otherwise permissible uses, releases and 
disclosures under Sec.  __.105(c) would not apply to research covered 
by this exemption. Respect for persons would be given more weight 
insofar as the subjects would now receive notice that research might 
take place, which is currently not required.
    Further, in many cases, other laws such as HIPAA also provide 
protections in the research context for the information that would be 
subject to this proposed exemption (e.g., clinical records), such that 
additional Common Rule requirements for consent may not be necessary in 
those contexts. Under HIPAA, these protections include, where 
appropriate, requirements to obtain the individual's authorization for 
future, secondary research uses of protected health information, or 
waiver of that authorization by an IRB or HIPAA Privacy Board. This 
proposal does not disturb those laws.
    The NPRM proposal limits the use of this exemption to cases in 
which individuals have been informed that the information may be used 
in research with the goal of ensuring that research under this 
exemption exhibits respect for persons. In particular, by ensuring that 
subjects are notified that their information may be used for research, 
this notice requirement may enhance subject autonomy.
    Alternative scopes for this provision are also proposed for 
consideration. A narrower scope could be envisioned that would limit 
the exemption to data generated by the Federal Government for which a 
privacy impact assessment has been conducted pursuant to section 208(b) 
of the E-Government Act of 2002, 44 U.S.C. 3601 et seq., that fully 
describes the ways that the information will be accessed, used, 
maintained, disseminated, and protected, and there is a formal written 
agreement between the investigator and the federal agency that requires 
the investigator to apply the same practices and safeguards as those 
addressed in the privacy impact assessment. Such a narrower 
interpretation might be easier to implement, and the line between Sec.  
__.104(e)(2) and (f)(2) would be clearer.
    Alternatively, it could be broadened to allow additional research 
uses of the information beyond the specific research for which the 
investigator or recipient entity obtained the information.
    The proposed exemption category could also be revised to change the 
manner in which respect for persons would be demonstrated by requiring 
that individuals have been given the opportunity to opt out of any 
secondary research with their identifiable private information. This 
would mean that subjects could exercise their autonomy to choose not to 
allow their information to be used, although this would not meet the 
even higher standard of fully informed active consent. Under this 
alternative, which would give prospective subjects the opportunity to 
opt out, it could be argued that the balance would be struck even more 
in favor of respect for persons by limiting the exemption to research 
where more than prior notice was required. This would restrict the 
exemption to research where an even greater measure of respect for 
persons had occurred, that is, that the individuals had been given the 
right to decline to participate in research, rather than simply being 
notified that such research was going to take place. Public comment is 
sought regarding this alternative approach as well.
    Finally, it also should be noted that section 511 of the Medicare 
Access and CHIP Reauthorization Act of 2015 requires the Secretary to 
issue a clarification or modification with respect to the application 
of these regulations to certain activities involving clinical data 
registries. This exemption category might allow certain research 
activities of these clinical data registries not otherwise covered by 
the proposed HIPAA-related exclusion at Sec.  __.101(b)(2)(iv) (i.e., 
when the clinical data registries are not part of a HIPAA covered 
entity or acting as a business associate), such as when a clinical data 
registry may receive information from a health care entity for research 
purposes.
(5) Questions for Public Comment
    49. Public comment is sought on the types of research that should 
fall under the proposed exemption. Should the proposed exemption be 
available to all types of research using identifiable data collected 
for non-research purposes or should the exemption be available only to 
a more limited subset of research? For example, should the proposed 
exemption apply only for research using records and information already 
subject to comprehensive privacy and other protections in other Federal 
laws (e.g., records held by the Federal Government subject to the 
Federal Privacy Act, or records governed by HIPAA or FERPA)?
    Depending upon the scope of the exemption, the relationship between 
this exemption and the exemption proposed at Sec.  __.104(f)(2) would 
need to be clarified. Since a major justification for including this 
exemption is to reduce burden on IRBs, should the proposed exemption 
apply only to research for which IRBs typically waive informed consent, 
that is, where the research could not practicably be carried out 
without a waiver of informed consent, and the rights and welfare of 
subjects will not be adversely affected by the waiver? Finally, is 
there a sufficient need for this exemption at all given the other 
proposed exclusions and exemptions?
    50. Public comment is sought regarding whether the proposed 
exemption should be limited to research in which individuals had been 
informed of the potential future research use of their information, and 
given the opportunity to opt out of having their identifiable private 
information used for research. If the proposed exemption should be 
limited in this way, what information should be included in the 
opportunity to opt out? If the opportunity to opt out is made a 
condition of the exemption category how should it be structured (e.g., 
how long and under what circumstances should it remain in effect) and 
what, if any, impact should the opt out have on other provisions of the 
rule, such as the ability of an IRB to waive informed consent for a 
subsequent research study using the individual's information? Are there 
other or alternative mechanisms that should be required to respect 
individuals' autonomy and other interests?
    51. Public comment is sought regarding what should constitute 
notice for purposes of this exemption category. Given the many 
different types of data that would be covered by this provision (e.g., 
data from private entities used for social or behavioral science 
research, government records for which laws already establish standards 
for notice, and data publicly available for harvesting from the 
internet), would it be possible to develop a uniform ``notice'' 
requirement? What type of notice, in terms of its dissemination and 
scope, should be considered to meet this requirement of the proposed 
exemption? With regard to the dissemination of the notice, should the 
notice requirement be permitted to be fulfilled through a general 
public notice, not specifically directed to individuals who are 
potential research subjects, such as the notice allowable under the 
Privacy Act? Would a prominent notice posted in all clinics or other 
relevant public places where information will be collected be 
acceptable? Should each individual whose data could be used receive 
their own notice, such as is required of direct treatment providers 
covered by the

[[Page 53965]]

HIPAA Privacy Rule? With regard to the content of the notice required 
by this proposed exemption, what kind of information should be included 
in the notice, such as the types of research that might be conducted, 
privacy safeguards, contact information, etc.?
    52. Public comment is sought on whether, on the other hand, prior 
notice is necessary. Is the notice requirement proposed for this 
exemption a meaningful and important measure to respect individual 
autonomy, particularly if the notice requirement could be fulfilled 
through a general public posting? Current practices suggest that IRBs 
will frequently waive informed consent for studies involving the 
secondary use of identifiable private information collected for non-
research purposes. If the exemption were to exclude the notice 
requirement, but continue to require application of the data security 
and privacy safeguards of Sec.  __.105 and restrict the use of 
identifiable private information to only purposes of the specific 
research for which the investigator obtained the information, would the 
exemption better strike a reasonable balance between respect for 
persons and beneficence, while eliminating the current requirement for 
IRB review?
    53. Public comment is sought as to whether this exemption would 
provide appropriate protections for research conducted by clinical data 
registries, while enabling these research activities to proceed without 
delay, and what should be included in guidance regarding such 
activities. Public comment is sought regarding the extent to which 
other exclusions or exemption categories would apply to research 
conducted by clinical data registries, such that the conditions of this 
exemption category would not apply.
d. Exemptions Subject to the Documentation Requirements of Sec.  
__.104(c), the Privacy Safeguards Described in Sec.  __.105, Limited 
IRB Review as Described in Sec.  __.111(a)(9), and Broad Consent in 
Accordance With Sec.  __.116(c)
i. NPRM Goals
    The goal of this proposed rule is to enable the conduct of research 
in the rapidly growing area of research involving biospecimens, 
especially genetic analyses, while recognizing the autonomy interests 
of people to decide whether or not to participate in this area of 
research. Some people have a particular interest in whether research 
will be carried out with their biospecimens, and want to exercise some 
control over their biospecimens. At the same time, biospecimen 
repositories are being created to enable innumerable research studies 
in the future, and the pace of technology development is such that the 
specific research studies to be carried out with those biospecimens is 
unknown at the time the biospecimens are collected.
ii. Current Rule
    The current Rule requires IRB review and approval of research 
involving identifiable private information, including individually 
identifiable biospecimens. IRB waiver of informed consent is allowable 
under the Common Rule, if the research study satisfies the criteria for 
waiver of informed consent. The current Rule also allows for research 
without consent when a biospecimen is used for research under 
conditions where the investigator does not possess information that 
would allow him or her to identify the person whose biospecimen is 
being studied.
iii. ANPRM Discussion
    The ANPRM considered requiring written general consent for 
secondary research use of biospecimens originally collected in research 
or non-research settings regardless of whether they include 
identifiers. The ANPRM proposed an excused or exempt category for 
research involving the secondary use of biospecimens originally 
collected for either research or non-research purposes if there was 
written broad consent for the research use of the biospecimens, 
typically obtained at the time of the original collection. The ANPRM 
also considered whether the broad consent should include check-off 
boxes allowing subjects to consent or decline consent for types of 
research raising unique concerns.
iv. NPRM Proposals
    The NPRM includes two exemptions proposed in Sec.  __.104(f) to 
facilitate storage, maintenance, and secondary research use of 
biospecimens and identifiable private information. Generally the 
exemption at Sec.  __.104(f)(1) will first be employed to allow the 
storage or maintenance for secondary research use of biospecimens or 
identifiable private information, by means of broad consent being 
obtained. Following that, the secondary research that will be conducted 
using such biospecimens or identifiable private information could often 
be exempted under Sec.  __.104(f)(2).
    A majority of commenters opposed the suggestion that there be 
consent requirements for the research use of non-identifiable 
biospecimens collected for purposes other than the current research 
study. Some commenters also favored requiring IRB review and approval 
for specific studies involving the use of identifiable private 
information and identifiable biospecimens, rather than permitting the 
use of a broad consent for future use to satisfy the regulatory 
requirement for consent. These commenters indicated that IRB review of 
specific research studies, and the IRB's consideration of whether a 
study-specific informed consent should be required or whether informed 
consent could be waived, was more protective of human subjects than the 
ANPRM recommendation permitting use of a broad consent for future use.
    Commenters to the 2011 ANPRM were mostly concerned with the cost 
and burden that would be imposed by the requirement to obtain consent 
for future research use of all biospecimens, regardless of 
identifiability. Commenters anticipated these costs to include 
obtaining consent from participants and the administrative efforts 
required to keep track of the consent status of biospecimens. Most 
commenters did not provide detailed cost estimates with their comments; 
data are specifically requested in response to this NPRM. In addition, 
estimates of the type and number of studies that could not be pursued 
using existing samples and data because of the absence of sufficient 
consent are requested. Comment is also sought on the value to the 
public and research participants of being asked their permission for 
research use of their data and biospecimens.
    While consideration was given to the opposition expressed by ANPRM 
commenters of a consent requirement for secondary research use of non-
identified biospecimens, the NPRM proposes to require that consent be 
obtained for the research use of non-identified biospecimens, but to 
allow for that consent to be broad. Thus, while consent would be 
required for the research use of non-identified biospecimens, one would 
not have to obtain study-specific consent for the research use of those 
biospecimens, drastically reducing the burden imposed by this new 
requirement.
    The NPRM proposal includes several protections for secondary 
research use of biospecimens in addition to the broad consent. Research 
activities falling under the exemption at Sec.  __.104(f) are subject 
to the requirements under proposed Sec.  __.104(c). This would require 
that exemption determinations be made by someone knowledgeable of the 
regulations, or by the to-be-created exemption determination tool (when 
utilized by an investigator or other

[[Page 53966]]

individual). Additionally, the documentation requirement would allow 
institutions to better know the scope and volume of secondary research 
studies conducted at an institution. Also note that Sec.  __.104(f)(1) 
requires that an IRB review the consent process through which broad 
consent would be obtained in the non-research context, to further allay 
ethical concerns about obtaining broad consent in clinical and other 
non-research contexts.
(1) Exemption for the Storage or Maintenance of Biospecimens or 
Identifiable Private Information for Secondary Research Use (NPRM at 
Sec.  __.104(f)(1))
    The first exemption in this group, at proposed Sec.  __.104(f)(1), 
is for storage or maintenance for secondary research use of 
biospecimens or identifiable private information that have been or will 
be acquired for research studies other than for the proposed research 
study, or for non-research purposes, if the following criteria are met:
     Written consent for the storage, maintenance, and 
secondary research use of the information or biospecimens is obtained 
using the broad consent template that the Secretary of HHS will 
develop. Oral consent, if obtained during the original data collection 
and in accordance with the elements of broad consent outlined in Sec.  
__.116(c) and (d)(3), would be satisfactory for the research use of 
identifiable private information initially acquired in accordance with 
activities excluded under Sec.  __.101(b)(2)(i) or exempt in accordance 
with Sec.  __.104(d)(3) or (4), or Sec.  __.104(e)(1); and
     The reviewing IRB conducts a limited IRB review of the 
process through which broad consent will be sought, and, in some cases, 
of the adequacy of the privacy safeguards described in Sec.  __.105.
    This exemption category only allows for the storage or maintenance 
for secondary research use of biospecimens or identifiable private 
information. Note that this exemption does not exempt the creation of 
any data or the actual new collection of any biospecimens from a person 
through a research interaction or intervention. (For example, if the 
proposed research activities involved creating a research repository of 
DNA samples that would be obtained from people through cheek swabs, the 
collection of the cheek swabs would mean that the creation of the 
research repository would require IRB review, and would not be exempt.) 
This exempt category is for secondary research use of biospecimens and 
identifiable private information and applies to biospecimens and 
identifiable private information that were initially collected for 
purposes other than the proposed research activity. The term `other 
than the proposed activity' here means that the information or 
biospecimens were or will be collected for a different research study 
or for a non-research purpose.
    In the case of a research study involving the actual new collection 
of biospecimens such as a clinical trial, the informed consent process 
could include obtaining informed consent for the original study (which 
study would not be exempt and would require IRB review and the usual 
type of consent document as required under Sec.  __.116(a) and (b)), 
and for secondary research use of the biospecimens. The informed 
consent form for the latter step (the secondary research use) could 
make use of the Secretary's template, in which case the biospecimen 
would be eligible for maintenance or storage under Sec.  __.104(f)(1) 
with limited IRB review or for a secondary research study under Sec.  
__.104(f)(2). If the Secretary's template for broad consent is not 
used, the storage or maintenance for secondary research use would not 
meet this exemption and the consent form would need to be reviewed and 
approved by an IRB, either along with the IRB review of the original 
study, if the maintenance and storage for secondary research is known 
and described, or later, if it is not. Note also that if the 
Secretary's template is not used, the Sec.  __.104(f)(2) exemption, as 
discussed below, would not apply to exempt any actual secondary 
research studies conducted using the stored biospecimens. IRB review 
would be needed for each of those studies, unless the research met one 
of the proposed exclusions at Sec.  __.101(b)(1) or (b)(3), or the 
exemption found in proposed Sec.  __.104(d)(2).
    This exemption requires written informed consent using the 
Secretary's template for broad consent for secondary research, or oral 
consent, in specified circumstances. This broad consent requirement 
will enable subjects the choice to include their biospecimens and 
information in this research. The consent form using the Secretary's 
template would include the information required in Sec.  __.116(c). 
Oral broad consent would also need to include all of the elements of 
consent at Sec.  __.116(c), and would only be permissible for the 
research use of identifiable private information, not biospecimens, 
when the identifiable private information was initially acquired as 
part of any of the following four excluded or exempt categories of 
research: (1) The exclusion related to research, not involving 
interventions, that involves the use of educational tests, survey 
procedures, interview procedures, or observation of public behavior 
(Sec.  __.101(b)(2)(i)); (2) the exemption related to research 
involving benign interventions (Sec.  __.104(d)(3)); (3) the exemption 
related to taste and food quality evaluation and consumer acceptance 
studies (Sec.  __.104(d)(4)); or (4) the exemption related to research 
involving the use of educational tests, survey procedures, interview 
procedures, or observation of public behavior (Sec.  __.104(e)(1)).
    It is proposed that oral broad consent only be permitted to satisfy 
these exemptions regarding the secondary use of identifiable private 
information (Sec.  __.104(f)(1) and (f)(2)) if the identifiable private 
information was initially acquired as part of any of the four above-
mentioned exclusion and exemption categories because these four 
categories are the only ones that are expected to typically involve 
some interaction with human subjects, and thus give investigators the 
opportunity to obtain oral consent from subjects for the secondary use 
of research data obtained as part of the initial research study.
    This exemption also requires adhering to the privacy safeguards 
described in the proposed section Sec.  __.105.
    The exemption also includes a requirement for limited IRB review 
(Sec.  __.111(a)(9)). The purpose of this limited IRB review is to 
ensure that the process of obtaining consent will occur in an 
appropriate way, because there may be some circumstances (for example, 
when someone is admitted for emergency care), when the individual is 
not able to make an informed considered decision. This IRB review will, 
for many institutions, be essentially a ``one-time'' event (as opposed 
to being needed for specific research studies); the IRB would review an 
overall general institutional protocol for the manner in which people 
can provide broad consent for the maintenance or storage of their 
biospecimens for future secondary research. Such a general 
institutional protocol would need to identify the circumstances in 
which broad consent would be sought for secondary research use of 
biospecimens so that the IRB could determine that these circumstances 
are consistent with the requirements for voluntary informed consent as 
described in the introductory language to proposed Sec.  __.116.
    In addition, if there will be a change in the way the biospecimens 
and information will be maintained for the secondary research purposes, 
rather

[[Page 53967]]

than simply changing the eligibility for secondary research status of 
biospecimens or information already being maintained for other 
purposes, then limited IRB review must also ensure that the biospecimen 
and information protection standards are still met. For example, if it 
is envisioned that the identifiable private information collected will 
be stored both at the institution obtaining the information, and also 
stored at a second institution, an IRB would also need to determine if 
the Sec.  __.105 privacy safeguards are adequate.
(2) Exemption for Secondary Research Use of Biospecimens or 
Identifiable Private Information where Broad Consent has been Sought 
and Obtained (NPRM at Sec.  __.104(f)(2))
    The second exemption in this exemption group, at Sec.  
__.104(f)(2), is for research involving the use of biospecimens or 
identifiable private information that have been stored or maintained 
for secondary research use, if consent for the storage and maintenance 
of the information and biospecimens was obtained as detailed using the 
broad consent template that the Secretary of HHS will develop. Note 
that oral broad consent would be allowed to the extent permitted under 
proposed Sec.  __.104(f)(1)(i)(A). If the investigator anticipates that 
individual research results will be provided to a research subject, the 
research may not be exempted under this provision and must be reviewed 
by the IRB and informed consent for the research must be obtained to 
the extent required by proposed Sec.  __.116(a) and (b).
    This exemption category at Sec.  __.104(f)(2) is for the actual 
secondary research studies that will be conducted using biospecimens or 
identifiable private information that have been stored for unspecified 
secondary research studies. This exemption does not include additional 
analyses being conducted to support or augment the original research 
study for which the information or biospecimens were originally 
collected.
    The proposed exemption category at Sec.  __.104(f)(2) requires that 
the privacy safeguards at Sec.  __.105 are met, and that broad consent 
to the earlier storage or maintenance of the biospecimens and 
information had already been obtained consistent with the requirements 
of Sec.  __.104(f)(1). This means that for secondary research using 
biospecimens informed consent must have been obtained using a consent 
form using the Secretary's template. It is presumed that research 
involving newborn blood spots would frequently take place using this 
provision.
    The rationale for these two exemptions is that they provide for 
obtaining broad consent from subjects for the research use of 
specimens, honoring the principle of respect for persons, they provide 
protections for the information involved through the privacy safeguards 
of Sec.  __.105, and the limited IRB review proposed at Sec.  
__.111(a)(9) ensures that the privacy safeguards and informed consent 
process are indeed adequate.
    The exemption at Sec.  __.104(f)(2) would not apply to research in 
which the investigator anticipates that research results will be 
provided to a subject. If it is anticipated that individual research 
results will be returned to subjects, then the research would not meet 
this exemption and IRB review and approval would be required, and 
informed consent would need to be obtained to the extent required by 
Sec.  __.116(a) and (b). If the investigator does not anticipate that 
individual research results will be provided to a research subject as 
part of the research plan, but later decides to return research results 
to subjects, an IRB must review and approve the plan for returning 
these results to the subjects. It is understood that the prospective 
IRB review provision set forth here does not override existing law, 
such as the HIPAA Privacy Rule or the Federal Privacy Act, which give 
individuals the right to access certain information about themselves in 
specified circumstances. In addition, it is recognized that clinical 
care needs may demand prompt reporting of findings to patients who are 
also human subjects, in which case it is expected that investigators 
would anticipate that such research results will be provided to a 
subject, and this exemption would not apply.
    It is generally recognized that where, for example, a series of 
genetic analyses are performed, in a significant percentage of 
instances investigators will be learning information, not necessarily 
related to the specific purpose of their studies, that would 
nonetheless be significant to participants in terms of making decisions 
about their health care. For example, it might be learned that a woman 
has a gene mutation that significantly increases her risk of breast or 
ovarian cancer. The proposed rule does not specifically impose any 
obligations on investigators to provide such information to 
participants, so long as the consent form is clear that no such 
information will be given to the participants. This could have a 
negative impact on the current efforts to increase the willingness of 
people to allow their biospecimens to be used in research, if they are 
less inclined to provide broad consent to such research when 
investigators are not making any commitment to return important 
information that is unexpectedly learned about a participant. This 
could lead some investigators to decide to include in their protocols 
provisions for returning such results to subjects. The consequence is 
that such protocols will not be eligible for the proposed exemption at 
Sec.  __.104(f)(2), and thus would undergo full IRB review primarily 
for the purpose of determining what information participants should be 
provided regarding such ``unexpected'' (i.e., not related to the 
purpose of the research) genetic findings. In contrast, if a study only 
involved use of biospecimens, and no results were to be returned to 
subjects, no IRB review would be required under the NPRM proposals 
unless IRB review is required by law (e.g., FDA-regulated devices).
    At the same time, it is likely that many IRBs do not have any 
particular unique expertise in making these determinations about 
returning results, which again could lead to inappropriate variability 
in disclosure from study to study, and would seem to be in conflict 
with the ethical goal of justice.
    One option that has been considered would be to create a federal 
panel of experts to make determinations about which unexpected findings 
should be disclosed to human subjects in research, and what information 
should be given to subjects about themselves. If this alternative 
proposal were adopted, then it would not be necessary to have full IRB 
review of these protocols. A consequence of this option would be that 
these types of studies could be exempt even if they proposed to return 
research results to subjects, so long as disclosures were made 
consistent with the rules announced by the federal panel. However, it 
is not clear that such a panel's guidance would be superior to that of 
IRBs.
v. Questions for Public Comment
    54. Public comment is sought on whether the NPRM's proposal of 
exemption Sec.  __.104(f)(2) is the best option, or whether there is a 
better way to balance respect for persons with facilitating research.
    55. Public comment is sought on whether and how the provision 
regarding the return of research results in the proposed exemption 
Sec.  __.104(f)(2) should be revised.
    56. Public comment is sought on whether there should be an 
additional exemption that would permit the

[[Page 53968]]

collection of biospecimens through minimally invasive procedures (e.g., 
cheek swab, saliva).
e. Applicability of Exemptions to the Subparts (NPRM at Sec.  
__.104(b); Current Rule at Footnote 1)
i. Current Rule
    In the current Common Rule, the application of the exemptions 
articulated in the current Common Rule in Sec.  __.101(b) to the 
subparts is specified through footnote 1 of the current Rule. It states 
that the exemptions do not apply to research involving prisoners, and 
are also limited in their application to research involving children. 
The current exemption at Sec.  __.101(b)(2) for research involving 
educational tests, survey or interview procedures or observations of 
public behavior does not apply to subpart D, except for research 
involving educational tests or observations of public behavior when the 
investigator does not participate in the activities being observed. The 
current exemptions do apply to subpart B.
ii. NPRM Proposals
    While the exemptions in the NPRM are based largely on exemptions in 
the current Common Rule, not all of the exemptions proposed in the NPRM 
will apply to subparts B-D. Language at Sec.  __.104(b) explains how 
the proposed exemptions may be applied to the subparts. The language at 
Sec.  __.104(b)(1) states that all of the exemptions at Sec.  __.104 
may be applied to research conducted under subpart B. Language at Sec.  
__.104(b)(2) states that none of the Sec.  __.104 exemptions may be 
applied to research conducted under subpart C, except for research 
aimed at a broader population that consists mostly of non-prisoners but 
that incidentally includes some number of prisoners. Finally, Sec.  
__.104(b)(3) states that the exemptions at Sec.  __.104(d)(1), (2), 
(4), Sec.  __.104(e)(2) and (f)(1) and (2) may be applied to research 
conducted under subpart D. The exemption at Sec.  __.104(e)(1) cannot 
be applied to research involving children under subpart D, because 
protections including IRB review and parental permission are 
appropriate for research involving educational tests, surveys or 
interview procedures, or observation of public behavior when the 
information collected may be individually identified and sensitive in 
nature.
    Although this NPRM does not propose changes to the HHS regulations 
at 45 CFR part 46, subparts B, C and D, consideration is being given to 
whether the proposed exemption categories articulated in Sec.  __.104 
should apply in research involving prisoners under subpart C, either if 
the research consists mostly of non-prisoners and only incidentally 
includes some number of prisoners, as proposed in the NPRM, or if the 
research intends to involve prisoners as research subjects. Originally 
developed in 1976 by the National Commission, subpart C has at times 
come under scrutiny for its restrictive construction. The subpart was 
written in the wake of harsh criticism regarding research abuses 
involving prisoners that occurred or became public in the 1960s and 
1970s. As a result, subpart C was written to permit research involving 
incarcerated persons only if the study fits one of four categories at 
45 CFR 46.306(a)(2) (an ``epidemiological waiver'' category was added 
in 2002 \51\), and requires an institution to ``certify'' to the 
Secretary, HHS, before research can proceed. An additional original 
restriction conveyed through footnote 1 of the current Common Rule 
specifies that research involving prisoners may not be considered 
exempt under any of the current exemption categories.
---------------------------------------------------------------------------

    \51\ 67 FR 62432 (Oct. 7, 2002).
---------------------------------------------------------------------------

    Public comment is requested on whether the revised exemption 
categories should be permitted to apply to research involving 
prisoners. Considerations include the preponderance of low-risk, socio-
behavioral research focused on prisoner welfare, substance abuse 
treatment, community reintegration, and services utilization; the 
occurrence of prisoner-subjects in databases or registries; and the 
broad interpretation of the subpart C ``prisoner'' definition that 
includes, for example, subjects in court-mandated residential substance 
abuse treatment.
ii. Questions for Public Comment
    57. Public comment is sought on whether research involving 
prisoners should be permitted to apply any or all of the exemption 
categories found at proposed Sec.  __.104, either if the research 
consists mostly of non-prisoners and only incidentally includes some 
number of prisoners, as proposed in the NPRM, or if the research 
intends to involve prisoners as research subjects.
    58. Would it be preferable for language at Sec.  __.104(b)(2) to 
resemble the 2002 epidemiologic waiver criteria and state that the 
exemptions apply except for research where prisoners are a particular 
focus of the research?
    59. Is the proposed application of the exemptions to subparts B and 
D appropriate?
f. What would change in the exemptions?
     All exemption language would be found at Sec.  __.104.
     The eight proposed exemptions in Sec.  __.104 would be 
divided into three groupings: (1) Low-risk interventions where no other 
requirement of the proposed rule (including informed consent and data 
protection) are necessary other than the determination and recording 
requirements (Sec.  __.104(d)); (2) research activities where the 
information protection measures at Sec.  __.105 must be applied (Sec.  
__.104(e)); (3) secondary research involving biospecimens and 
identifiable private information that requires application of privacy 
safeguards at proposed Sec.  __.105, broad consent as discussed at 
proposed Sec.  __.116(c), and limited IRB review as discussed at 
proposed Sec.  __.111(a)(9).
     Existing exemption categories 1, 5, and 6 (current Sec.  
__.101(b)(1), (5), and (6)) would be retained at Sec.  __.104(d)(1), 
(2), and (4). Specifically the current exemption for research on public 
benefit programs or demonstration projects (Sec.  __.101(b)(5) in the 
current Rule; Sec.  __.104(d)(2) in the NPRM) would be clarified and 
OHRP's guidance would be changed to include the applicability of the 
exemption to cover research on public benefit and service programs that 
an agency does not itself administer through its own employees or 
agents. A requirement for publishing a list of studies under this 
exemption would apply for Federal agencies or departments conducting or 
supporting such studies.
     A new exemption would be created for certain research 
involving benign interventions.
     A new exemption would be created for certain research 
involving educational tests, survey or interview procedures, or 
observation of public behavior where identifiable private information 
was recorded so long as data protection standards are met.
     A new exemption would be created for secondary research 
use of identifiable private information originally collected for non-
research purposes.
     A new exemption would be created for activities relating 
to the storage and maintenance, for secondary research use, of 
biospecimens and identifiable private information.
     A new exemption would be created to exempt secondary 
research studies

[[Page 53969]]

that would use the biospecimens and identifiable private information 
stored or maintained under the above new exemption.

B. Proposed Changes To Obtaining, Waiving, and Documenting Informed 
Consent (Sec. Sec.  __.116 and __.117)

    The NPRM proposals address: (1) The organization and presentation 
of information included in the consent document and the process to 
facilitate a prospective subject's decision about whether to 
participate in research; (2) the elements of consent, basic and 
additional; (3) broad consent to the storage or maintenance for 
secondary research use of biospecimens and identifiable private 
information, and the use of such stored biospecimens and information 
for specific research studies; and (4) attendant changes in the waiver 
or alteration criteria for consent.
    The NPRM proposes several changes to the Common Rule with regard to 
the elements of informed consent and when it must be obtained (see 
further discussion below regarding proposed changes to the conditions 
for waiver of consent). In addition, it makes several new proposals 
that were not included in the ANPRM questions, but are offered in 
response to public comments received as well as internal discussions 
within HHS and with the other Common Rule agencies.
    These include the development of a Secretary's template, which will 
be issued in draft for public comment at a later date (the NPRM at 
Sec.  __.116(d)) for broad consent to the storage or maintenance for 
secondary research use of biospecimens, and identifiable private 
information and the use of such stored biospecimens and information for 
specific research studies. Broad consent would be permissible for the 
storage or maintenance for secondary research use of such information 
and biospecimens that were originally collected for either research 
studies other than the proposed research or non-research purposes. This 
broad consent document would meet the consent requirements for the 
storage or maintenance of biospecimens and identifiable private 
information for secondary research, as well as the use of such stored 
material for individual research studies.
    Because biospecimens and information that have been collected for 
clinical use or purposes other than for the proposed research are often 
an important source of information and material for investigators, and 
the re-use of existing information and materials can be an efficient 
mechanism for conducting research without presenting additional 
physical or psychological risks to the individual, it seems prudent to 
consider changes to current regulations relating to those issues. Some 
critics, including potential and former research subjects, object to 
research performed on a person's biospecimens or information without 
consent. Conversely, investigators and patient advocacy groups are 
concerned that the need for informed consent for every use of a 
biospecimen or data element will greatly inhibit research. They worry 
that obtaining individual consent for each separate research study will 
create unmanageable logistical demands, making valuable research 
impossible.
    As an additional means of increasing transparency and facilitating 
the development of more informative informed consent forms, it is 
proposed that a copy of the final version of the consent form for 
clinical trials conducted or supported by a Common Rule department or 
agency would need to be posted on a publicly available Federal Web 
site. Within 60 days after the trial was closed to recruitment, the 
awardee or the federal department or agency conducting the clinical 
trial would be required to post the consent document, the name of the 
clinical trial and information about whom to contact for additional 
details about the trial.
    In addition to the specific changes proposed to Sec.  __.116, 
comment is sought on whether Common Rule agencies should modify the 
definition of ``legally authorized representative'' (LAR). The current 
Rule defines LAR at Sec.  __.102(c) as an individual or judicial or 
other body authorized under applicable law to consent on behalf of a 
prospective subject to the subject's participation in the procedure(s) 
involved in the research. While the NPRM proposes to retain this 
language, OHRP is aware that this definition has been problematic for 
states in which there is no applicable law permitting an LAR to consent 
in either a clinical or a research context. In the absence of such a 
law, it is almost always the case that community or other standards 
(such as institutional policies) define hierarchies or identify 
individuals who may provide legally acceptable consent, for clinical 
(non-research) purposes, on behalf of others who cannot consent for 
themselves. However, the current regulations are interpreted to not 
allow such standards to constitute applicable law for purposes of the 
regulations, and thus such individuals are not considered legally 
authorized representatives for purposes of the Common Rule. Concerns 
that the Common Rule's current definition of LAR may be inappropriately 
hindering the conduct of research with subjects who lack capacity to 
consent have been raised by the Secretary's Advisory Committee on Human 
Research Protections (SACHRP),\52\ the Presidential Commission for the 
Study of Bioethical Issues,\53\ and others in the research community.
---------------------------------------------------------------------------

    \52\ Secretary's Advisory Committee on Human Research 
Protections. (2009, March 4). Recommendations from the Subcommittee 
for the Inclusion of Individuals with Impaired Decision Making in 
Research (SIIIDR). Retrieved from Office for Human Research 
Protections: http://www.hhs.gov/ohrp/sachrp/20090715letterattach.html.
    \53\ Presidential Commission for the Study of Bioethical Issues. 
(2015). Gray Matters: Topics at Intersection of Neuroscience, Ethics 
and Society. Retrieved from Projects: http://bioethics.gov/sites/default/files/GrayMatter_V2_508.pdf.
---------------------------------------------------------------------------

    Comment is therefore sought on whether a revision that would expand 
the current definition to also permit an LAR to be defined by an 
accepted common practice standard that is used in a state for 
determining who can legally consent to clinical care would be 
consistent with the ethical principles underlying the Common Rule. Such 
a revision would broaden the definition of LAR and permit investigators 
to use accepted common practice, such as an established state or local 
hierarchy, to allow another person to provide consent to research 
participation. In the absence of such a revision, it would remain the 
case that in certain states, there would appear to be no way (short of 
taking the often difficult legal step of obtaining the appointment of a 
legal guardian) to enroll subjects lacking decision-making capacity in 
research studies. Given that the current interpretation of current 
Sec.  __.102(c) generally is based on the proposition that the person 
who can legally consent on behalf of someone else for a particular 
clinical procedure to take place should have the authority to consent 
for research purposes, it could be viewed as inappropriate to maintain 
the current Rule, which produces different results in terms of when 
research can take place in those states that have specific laws 
governing such clinical consent and those that accomplish the same 
legal outcome through less formal regimes.
1. Required Elements of Informed Consent (NPRM at Sec.  __.116(a), (b))
a. NPRM Goal
    Many claim that consent forms have evolved to protect institutions 
rather than to provide potential research subjects with some of the 
most important pieces of information that a person would need in order 
to make an informed decision about whether to

[[Page 53970]]

enroll in a research study.\54\ Instead of presenting the information 
in a way that is most helpful to prospective subjects--such as 
explaining why someone might want to choose not to enroll--the forms 
often function as sales documents or as a means to protect against 
institutional liability rather than as genuine aids to good decision-
making.\55\ There is also a growing body of literature that suggests 
informed consent forms have grown too lengthy and complex, adversely 
affecting their ability to convey the information needed for 
prospective participants to make an informed decision about 
participating in research.\56\
---------------------------------------------------------------------------

    \54\ Levine RJ. Informed consent: Some challenges to the 
universal validity of the western model. J Law Med Ethics 1991;19(3-
4):207-213.
    \55\ Menikoff J, Richards E. What the Doctor Didn't Say: The 
Hidden Truth about Medical Research. New York, NY: Oxford University 
Press; 2006:113-123.
    \56\ Beardsley E et al. Longer Consent Forms for Clinical Trials 
Compromise Patient Understanding: So Why Are They Lengthening? 
Journal of Clinical Oncology. 2007 Mar 20;25(9):e13-4.
---------------------------------------------------------------------------

    The goal of the proposed changes to the informed consent form and 
process is to facilitate prospective subjects' decision about whether 
or not to participate in a research study, thereby enhancing autonomy.
b. Current Rule
    Currently, under the Common Rule, investigators generally must 
ensure that the subjects' informed consent to participate in research 
is obtained.\57\ The regulations currently require that the consent 
forms include at least eight specific items of information. Various 
aspects of the consent forms have been heavily criticized, as have the 
amount of time IRBs devote to editing and revising them.
---------------------------------------------------------------------------

    \57\ For general requirements for informed consent see Sec.  
__.116 in the current Rule, and 21 CFR 50.20, .25 for FDA's 
comparable requirements. There are provisions under the Common Rule, 
that allow for the waiver of some or all of the elements of informed 
consent (see Sec.  __.116(c) and (d)). The Federal Food, Drug, and 
Cosmetic Act limits the circumstances under which informed consent 
can be waived. See, e.g., section 520(g) (21 U.S.C. 360j(g)) Thus, 
FDA regulations contain only two exceptions from informed consent 
under 21 CFR 50.23-24.
---------------------------------------------------------------------------

c. ANPRM Discussion
    The ANPRM discussed revising the regulations to provide greater 
specificity about how consent forms should be written and what 
information they should contain. The goal would be consent documents 
that are shorter, when appropriate, more readily understood, less 
confusing, that contain all of the key information in sufficient 
detail, and that can serve as an aid to help someone make an informed 
decision about whether to participate in a study.
d. NPRM Proposals
    Public comments were largely in favor of finding ways to improve 
consent forms. However, commenters cited several systemic concerns that 
could be obstacles to shortening and simplifying forms, such as 
regulatory, legal, and institutional requirements, and the complexity 
of some studies. Of those responding to questions about the causative 
factors, blame for making forms long and complex was shared by sponsors 
of clinical trials, IRBs, regulatory agencies, and institutional legal 
counsel. The types of information cited as contributing to the 
excessive lengths of forms included the requirement to describe all 
reasonably foreseeable research risks and the complexity of study 
procedures. There was no consensus on how to better explain 
alternatives to research participation and few comments were submitted 
on this topic.
    Commenters offered a few suggestions for modifying or deleting the 
required elements of consent, such as removing boilerplate language 
that only protects institutions and research sponsors, as well as 
removing some of the required elements for minimal risk research. 
However, many felt that guidance, rather than regulatory change, would 
better improve the development of consent forms. Although many 
commenters noted the need for shorter and more comprehensible consent 
forms, most felt that the required elements of consent articulated in 
the Common Rule are sufficient. Commenters overwhelmingly supported the 
goals articulated in the ANPRM, but cautioned against an overly 
prescriptive or rigid approach to consent forms. However, several 
commenters requested guidance on what might be included in a consent 
form for future research use of identifiable information and 
identifiable biospecimens to ensure that such forms satisfied the 
consent requirements of the Common Rule.
    A majority of commenters supported the development of regulations 
or guidance designed to encourage assessment of the extent to which 
human subjects comprehend consent forms, at least for certain types of 
higher risk studies or certain types of subject populations. Others 
argued that the regulations at Sec.  __.116 already contain language 
implying the need to ensure comprehension through the use of the terms 
``legally effective informed consent'' and ``language understandable to 
the subject.''
    Finally, many commenters supported making changes to HIPAA 
authorization requirements, as necessary, to conform to provisions of 
the Common Rule. In addition, most commenters were supportive of 
requiring investigators to disclose in consent forms certain 
information about the financial relationships they have with study 
sponsors.
    To that end, the NPRM proposes adding new language to the 
introductory text of Sec.  __.116 to address the questions asked in the 
ANPRM about strengthening the informed consent requirements. It 
reorients the language to emphasize the need to first provide essential 
information that a reasonable person would want to know in order to 
make an informed decision about whether to participate, and to provide 
an opportunity to discuss that information. It requires that the 
information be presented in sufficient detail relating to the specific 
research. Furthermore, in recognition of the complaints that current 
consent forms are too commonly complicated documents that primarily are 
used to protect sponsors from legal liability, the NPRM would require 
(as described in the in the revised introductory language to Sec.  
__.116) that the information in these forms be organized and presented 
in a way that did not merely provide lists of isolated facts, but 
rather facilitated the prospective subject's or representative's 
understanding of the reasons why one might or might not want to 
participate. For example, for some research studies, it could be 
important for the discussion of the purpose of the research and the 
reasonably foreseeable risks of the research to be discussed together 
so that prospective subjects would better understand how participation 
in the study might alter their clinical care and ultimately, their 
health.
    It is also proposed that in obtaining informed consent, the 
investigator would be required to present first the information 
required by this section, before providing other information, if any, 
to the subject. This would mean that the consent document could only 
include the elements of consent that were required by the rule, with 
any other information included in an appendix. This is intended to lead 
to substantially shorter consent forms, with prospective subjects 
receiving the most important information in the body of these 
relatively short forms, instead of that key information being buried in 
a long and overly complex document.
    Public comments did not provide consensus on desirable changes to 
the elements of informed consent. Thus,

[[Page 53971]]

this language aims to emphasize the necessity of addressing the basic 
elements of informed consent, as described in Sec.  __.116(a), in a 
user-friendly but sufficiently detailed manner that facilitates 
comprehension of the risks and potential benefits of the research. 
Because commenters agree that informed consent forms should be written 
in appropriate language, this proposal reinforces the need to include 
information using language understandable to the subject. This goal is 
consistent with Federal Plain Language guidelines and the Federal Plain 
Writing Act of 2010. The Secretary will publish guidance at a later 
time to explain how consent forms can be written in order to comply 
with the requirements of this policy. It is not envisioned that the 
regulations would require a formal assessment to evaluate an 
individual's competency, but that such a practice may be appropriate 
for certain populations. That this ambiguity already exists in the 
current regulations with regard to what constitutes ``legally effective 
informed consent'' is acknowledged.
    In addition, the NPRM proposes to clarify in the introductory 
language at Sec.  __.116 that if a HIPAA authorization is combined with 
a consent form, the authorization elements required by 45 CFR 164.508 
must be included in the consent document and not the appendices. In 
other words, when consent is combined with authorization, the 
authorization elements should be considered to constitute one of the 
required elements of consent.
    Since research with non-identified data does not involve ``human 
subjects'' under proposed Sec.  __.102(e), it is proposed that a new 
element of informed consent be required to better ensure that subjects 
are informed of the possibility that identifiers collected as part of a 
research study could be removed from the data and then used for 
secondary research studies without the protections provided by this 
policy. The new basic element of consent at Sec.  __.116(a)(9) would 
apply to all research collecting identifiable private information. 
Based on the investigator's plans, the informed consent form and 
process would need to inform subjects either that: (1) Identifiers 
might be removed from the data and that the non-identified data could 
be used for future research studies or distributed to another 
investigator for future research studies without additional informed 
consent from the subject or the representative, if this might be a 
possibility; or (2) the subject's data collected as part of the 
research would not be used or distributed for future research studies, 
even in a non-identified form. This proposed additional element of 
informed consent is intended to create greater transparency and enable 
prospective research subjects to make a more informed decision about 
whether to participate in research. Prospective subjects can always 
decline to participate in the initial research if they object to the 
statement provided. These changes would not apply to ongoing human 
subjects research in which human subjects were involved prior to the 
effective date of this rule.
    It is anticipated that very few investigators will elect to offer 
the option to restrict the future research use of non-identified data, 
in part because of the challenges of marking and tracking such 
decisions. However, should they offer this option, then institutions 
and investigators will have to develop a system for tracking 
impermissible uses of non-identified information. Since most 
investigators will likely elect to inform subjects that identifiers 
might be removed from the data and distributed for future research 
without additional informed consent, it would be reasonable for 
investigators and institutions to generally assume that the secondary 
research use of non-identified information would be permissible unless 
marked otherwise.
    It is possible that investigators could choose to include 
additional statements about their plans to use non-identified data for 
future research studies. For example, investigators could agree to give 
subjects an option about whether subjects' non-identified research data 
could be used for future research studies, or could agree to seek 
additional informed consent from subjects before using or sharing non-
identified data for future research studies. However, it is anticipated 
that such commitments by investigators would be uncommon, and so the 
NPRM does not propose including such statements in the informed consent 
form or process. If such commitments about the future use of non-
identified information were made by investigators in the informed 
consent form or process, investigators would need to satisfy these 
commitments, which would also require the development of a tracking 
system.
    The NPRM also proposes adding three additional elements of consent 
at Sec.  __.116(b)(7)-(9) that, when appropriate, would be required to 
be included in the informed consent form and process. These three 
additional elements of consent all pertain to issues that have become 
more relevant in recent years as science has advanced and the nature of 
research has changed. The proposed new element at Sec.  __.116(b)(7) 
would require that prospective subjects be informed that their 
biospecimens may be used for commercial profit and whether the subject 
will or will not share in this commercial profit. The proposed new 
element at Sec.  __.116(b)(8) would require that prospective subjects 
be informed of whether clinically relevant research results, including 
individual research results, will be disclosed to subjects, and if so, 
under what conditions. The proposed new element at Sec.  __.116(b)(9) 
would provide subjects or their legally authorized representatives with 
an option to consent, or refuse to consent, to investigators re-
contacting the subject to seek additional information or biospecimens 
or to discuss participation in another research study. Since the 
information that would be required to be disclosed under these three 
proposed additional elements of consent is often relevant to an 
individual's decision of whether to participate in a research study, 
currently such information is sometimes included in informed consent 
forms under the current Common Rule. The NPRM proposes to require 
inclusion of these additional elements, when appropriate, to better 
ensure that prospective subjects are more consistently provided with 
this information when it is information that a reasonable person would 
want to know in order to make an informed decision about whether to 
participate in a research study. These three proposed additional 
elements of consent are also relevant to seeking an individual's broad 
consent to the storage, maintenance, and secondary research use of 
biospecimens or identifiable private information, so it is proposed 
that broad consent obtained under Sec.  __.116(c) also include these 
additional elements, when applicable. These clarifications and 
additions would have to meet the documentation requirements at Sec.  
__.117(b)(1)-(2).
e. What would change?
     New language would strengthen the informed consent 
requirements to make sure that the most appropriate information is 
presented to prospective subjects in sufficient detail and in a format 
that is tied to understandability.
     New language would clarify that, when a HIPAA 
authorization is combined with consent, the HIPAA authorization 
elements must be part of the core elements of the consent.
     When identifiable private information is collected for 
research purposes, consent would be required to notify subjects if 
their non-identified

[[Page 53972]]

information could be utilized for future research studies without 
additional consent.
     The Secretary will publish guidance in the future to 
explain how consent forms can be written to comply with the regulatory 
requirements.
     Three additional elements of consent would be required, 
when appropriate.
f. Question for Public Comment
    60. What topics should be addressed in future guidance on improving 
the understandability of informed consent?
2. Broad Consent to the Storage, Maintenance and Secondary Research Use 
of Biospecimens and Identifiable Private Information (NPRM at Sec.  
__.116(c), (d)).
a. NPRM Goal
    One of the primary objectives of the NPRM is to make the strength 
of protections commensurate with the level of risks of the research, 
and by so doing, reduce unnecessary administrative burdens on research. 
That objective has been viewed as being particularly relevant to 
research involving only secondary use of biospecimens and identified 
data, which is relatively low-risk if appropriate protections of 
privacy and confidentiality are in place, including protections against 
the misuse of biospecimens or data that could cause harm to research 
subjects.
b. Current Rule
    The increasing use of information and biospecimens in research, 
often into the future and beyond the point at which an individual is 
directly involved in the information or biospecimen collection, 
requires rethinking the elements of consent in those circumstances to 
ensure that potential research subjects understand how their 
information or biospecimens might be used as well as the risks and 
potential benefits of such use. Critics of the existing rules have 
observed that the current requirements for informed consent for future 
research with pre-existing information and biospecimens are confusing 
and consume substantial amounts of investigators' and IRBs' time and 
resources.
    Under the current requirements of the Common Rule, if identifiers 
are removed, biospecimens and data that have been collected for 
purposes other than the proposed research can be used without any 
requirement for informed consent. Similarly, under the HIPAA Privacy 
Rule, if data are de-identified or HIPAA identifiers do not accompany 
biospecimens, then the Privacy Rule does not apply. When identifiers 
have not been removed, under the Common Rule investigators may be 
allowed in certain situations to obtain a consent that is broader than 
for a specific research study, such as for a research repository that 
involves obtaining biospecimens from living individuals to create a 
repository for future research studies. In these cases, an IRB may 
determine that the original consent for the creation of the research 
repository satisfies the requirements of the Common Rule for the 
conduct of the future research, provided that the elements of consent 
under Sec.  __.116 continue to be satisfied for the future research. 
Despite this existing flexibility in the Common Rule, it is believed 
that the current elements of consent required under Sec.  __.116 often 
do not continue to be satisfied for the future research.
    With respect to HIPAA, HHS's prior interpretation of the HIPAA 
Privacy Rule was that authorizations for research needed to be study-
specific, and thus, that such authorizations could not authorize 
certain future unspecified research. However, in January 2013, the 
Office for Civil Rights modified its prior interpretation.\58\ Under 
the new interpretation, an authorization now may be obtained from an 
individual for uses and disclosures of protected health information for 
future research purposes, so long as the authorization adequately 
describes the future research such that it would be reasonable for the 
individual to expect that his or her protected health information could 
be used or disclosed for the future research purposes.
---------------------------------------------------------------------------

    \58\ 78 FR 5611-5613 (Jan 25, 2013).
---------------------------------------------------------------------------

c. ANPRM Discussion
    The ANPRM suggested generally requiring written consent for 
research use of any biospecimens collected for clinical purposes after 
the effective date of the new rules (such as research with excess 
pathological specimens). Such consent could be obtained by use of a 
brief standard consent form agreeing to generally permit future 
research. This brief consent could be broad enough to cover all 
biospecimens to be collected related to a particular set of encounters 
with an institution (e.g., hospitalization) or even to any biospecimens 
to be collected at any time by that institution. These studies using 
biospecimens collected for clinical purposes would also fall under the 
expanded and revised exempt categories, and thus would not require IRB 
review or any routine administrative or IRB review but would be subject 
to the data security and information protection standards. This 
discussed modification would conform the rules for research use of 
clinically collected biospecimens to the rules for biospecimens 
collected for research purposes. The general rule would be that a 
person needs to give consent, in writing, for research use of their 
biospecimens, though that consent need not be study-specific, and could 
cover open-ended future research. The ANPRM envisioned that consent 
could be waived in certain limited circumstances and sought comment on 
appropriate criteria for waiving consent.
    The ANPRM suggested that this standardized broad consent form would 
permit the subject to say no to all future research. In addition, the 
ANPRM acknowledged that there are likely to be a handful of special 
categories of research with biospecimens that, given the unique 
concerns they might raise for a significant segment of the public, 
could be dealt with by check-off boxes allowing subjects to separately 
agree (or not) to that particular type of research. More specifically, 
the ANPRM asked whether certain flexible consent requirements could be 
imposed on some of these studies that would permit the use of a broad 
consent for future use, with a requirement that a subject's specific 
consent would be required before their biospecimens could be used for 
special categories of research.
    Further, the ANPRM suggested maintaining the current prohibition 
that participation in a research study (such as a clinical trial) could 
not be conditioned on agreeing to allow future open-ended research 
using a biospecimen. With regard to the secondary research use of pre-
existing data, on those occasions when oral consent was acceptable 
under the regulations for the initial data collection, the ANPRM 
envisioned that subjects would have typically provided their oral 
consent for future research at the time of the initial data collection; 
a written consent form would not have to be signed in that 
circumstance.
    The ANPRM also noted that there would be rules that would allow for 
waiver of consent under specified circumstances, though those 
conditions would not necessarily be the same as those for other types 
of research.
d. NPRM Proposal
    Similar to what was discussed in the 2011 ANPRM, the NPRM proposes 
to allow broad consent to cover the storage or maintenance for 
secondary research use of biospecimens and identifiable private 
information. Broad consent would be permissible for the storage or 
maintenance for secondary research of such information and biospecimens 
that

[[Page 53973]]

were originally collected for either research studies other than the 
proposed research or non-research purposes. The broad consent document 
would also meet the consent requirement for the use of such stored 
biospecimens and information for individual research studies. As is 
currently the case, consent would not be required for the secondary 
research use of non-identified private information, such as the 
research use of medical records that have had all identifiers removed. 
The NPRM also proposes to facilitate research that uses information or 
biospecimens collected for purposes other than the currently proposed 
research by adding a new consent provision for such research at Sec.  
__.116(c), which would permit individuals to provide broad consent for 
the storage or maintenance for secondary research use of their 
information and biospecimens that would not be study-specific, and 
would be sufficient to satisfy the consent requirement for two proposed 
exemptions at Sec.  __.104(f)(1) and (f)(2).
    Since it is proposed that the definition of human subject be 
expanded to include all biospecimens, the NPRM proposes to facilitate 
research using biospecimens by permitting broad consent to be obtained 
for their storage or maintenance for secondary research. In addition, a 
new exemption at Sec.  __.104(f)(2) would permit the secondary research 
use of biospecimens without a subject being given information about the 
specific research study if broad consent under Sec.  __.116(c) and (d) 
was obtained and the privacy safeguards at Sec.  __.105 were met.
    Public comments on the 2011 ANPRM revealed variable opinions on the 
issue of broad consent. Several commenters indicated that there is no 
need for additional regulations, with one university stating that it 
``strongly opposes more restrictive regulations about the use of these 
biospecimens and sees no need to change the current regulations, even 
or perhaps especially in the case of secondary data analysis.'' Other 
commenters opposed broad consent, stating that investigators and 
clinicians should obtain specific consent from individuals for each 
research project. This opposition was made on the ethical grounds that 
because individuals are not fully informed of specific research 
purposes for broad consent, they can never be truly informed about the 
use of their data. In contrast, other commenters expressed clear 
support for general consent for secondary research use of biospecimens 
and data collected during research to exempt the research from IRB 
review, noting that ``we support the suggestion in the ANPRM to 
encourage general consent for the secondary research use of 
biospecimens and data and where this is not obtained IRB review is 
required.'' Other commenters favored requiring IRB review over 
permitting the use of a broad consent to approve secondary research use 
of identifiable data or biospecimens. These commenters believed that 
IRB consideration of consent requirements for individual research 
studies was more protective of human subjects than the ANPRM 
suggestions to permit broad consent for future use.
    It is envisioned that the proposed broad consent provision would be 
used by institutions and investigators to give individuals the choice 
to either allow or disallow the use of their biospecimens and 
identifiable private information for secondary research. In some cases, 
institutions would be expected to seek broad consent under Sec.  
__.116(c) and (d) as part of a research protocol to create a research 
repository of biospecimens or information. However, in other cases it 
is expected that institutions, particularly institutions that do not 
typically conduct human subjects research, might not develop a research 
protocol to create a research repository, but still choose to seek 
broad consent from individuals for the research use of their 
biospecimens or identifiable private information. In such cases, these 
institutions might simply ``tag'' biospecimens and information as 
either available or not available for secondary research.
    Since broad consent is a different form of informed consent than 
informed consent for a specific research study, in which individuals 
must be given information about a particular research study to be 
conducted with their biospecimens and information, the proposed 
requirements for broad consent under Sec.  __.116(c) and (d) would 
include several of the basic and additional elements of informed 
consent under Sec.  __.116(a) and (b), but not all, and would include 
several additional required elements. The proposed elements of broad 
consent are intended to ensure that the individual would be provided 
with sufficient information to make an informed decision about whether 
to agree to provide broad consent for a wide variety of research that 
may be unforeseen at the time in which consent is being sought.
    The NPRM proposes to require that the broad consent describe the 
biospecimens and identifiable private information that would be covered 
by the consent, recognizing that the biospecimens and information to be 
used in future research studies might be collected after the consent 
was obtained. Broad consent for the research use of biospecimens or 
identifiable private information that were originally collected for a 
research study would generally be described in the consent document for 
the study that would be generating the research biospecimens or 
information. Therefore, it is proposed that broad consent to the 
secondary research use of biospecimens and identifiable private 
information collected as part of a research study could cover all such 
research material.
    However, in the non-research context, it is recognized that the 
biospecimens and information that the subject would be asked to permit 
to be stored or maintained and used for a wide range of secondary 
research studies would not be as readily understood as in the research 
context, since such non-research collections are usually less 
predictable or defined. Therefore, the NPRM proposes that broad consent 
for the research use of biospecimens or identifiable private 
information obtained for non-research purposes would be limited to 
covering either or both of the following: (1) Biospecimens or 
identifiable private information that exist at the time at which broad 
consent is sought; and (2) biospecimens or identifiable private 
information that will be collected up to 10 years after broad consent 
is obtained for adult subjects, and, for research involving children as 
subjects, biospecimens or identifiable private information that will be 
collected up to 10 years after broad consent is obtained or until the 
child reaches the legal age of consent to the treatments or procedures 
involved in the research, whichever comes first.
    The rationale for these limitations is that individuals will not 
know what biospecimens and information about them will be collected by 
an institution in the future. The 10-year time limit may make it more 
likely that an individual will have a better understanding of the 
biospecimens and information that would be covered by the broad 
consent, and may be a sufficiently long enough time period to 
appropriately facilitate secondary research using biospecimens and 
information. The NPRM proposes to include the standard for who is a 
child based upon the definition of ``children'' as defined at 45 CFR 
46.402(a). At the time the child became an adult, the broad consent or 
permission would no longer be valid and either broad consent would need 
to be sought from the child-turned adult, or the investigator would 
need to seek a waiver of informed consent in order to use the 
individual's

[[Page 53974]]

biospecimens or identifiable private information for research, unless 
one of the exclusions or exemptions were applicable.
    The Common Rule departments and agencies contemplated proposing 
that the scope of broad consent to secondary research use of 
individually identifiable clinical information or biospecimens that 
were originally collected for non-research purposes would be limited to 
(1) clinical information and biospecimens already existing at the 
institution at the time broad consent was sought, and (2) clinical 
information and biospecimens collected as part of an identified 
clinical encounter. Although it was recognized that this limitation 
related to an identified clinical encounter would give individuals more 
meaningful information about the scope of future clinical information 
and biospecimens that would be covered by their broad consent, it was 
determined that limiting the scope of the broad consent in this manner 
would be very difficult to implement and would require rigorous 
tracking on an individual-subject basis. Therefore, this proposal was 
not included in the NPRM, and was instead replaced with the above 
proposal that uses a limitation based on a period of years.
    In addition, the Common Rule departments and agencies contemplated 
proposing that for nonclinical information collected for non-research 
purposes (e.g., education and court records, financial records, 
military records, employee records, or motor vehicle records), broad 
consent would only be required to include a clear description of the 
types of records or information that were or will be collected and the 
period of time or event during which information collection may occur. 
However, it was decided that all biospecimens and identifiable private 
information originally collected for non-research purposes should be 
bound by the same limitations, regardless of whether the materials were 
originally collected for clinical or nonclinical purposes.
    The proposed element of broad consent, at (Sec.  __.116(c)(1)(iv)), 
includes a requirement that subjects be informed that they may withdraw 
consent, if feasible, for research use or distribution of the subject's 
information or biospecimens at any time without penalty or loss of 
benefits to which the subject is otherwise entitled. Information that 
has been stripped of identifiers might not be traceable. Thus, it might 
not be feasible to withdraw consent for future use or distribution in 
this case. If, however, an investigator committed to permitting a 
subject to discontinue the use of such information, it is expected that 
the investigator would honor this commitment by not stripping 
identifiers. The regulations would not require investigators to make 
such a commitment.
    Another of the proposed elements of broad consent, at (Sec.  
__.116(c)(1)(viii)), relates to the public posting of non-identifiable 
data about a subject. This proposed element of broad consent would 
include an option, when relevant, for an adult subject or the subject's 
legally authorized representative to consent or refuse to consent, to 
the inclusion of the subject's data, with removal of the identifiers 
listed in the HIPAA Privacy Rule at 45 CFR 164.514(b)(2)(i)(A) through 
(Q), in a database that is publicly available and openly accessible to 
anyone. This provision is being proposed in the context of increasing 
interest in inviting study participants to allow their study data, in 
some cases including genomic data, to be made publicly available in 
order to maximize the potential for research that spurs increased 
understanding of disease processes. Under this provision, the consent 
document would be required to prominently note the option for the 
participant to allow the investigator to publically post (e.g., on a 
Web site) the participant's genomic or other potentially identifiable 
sensitive information, and to include a description of the risks 
associated with public access to the data.
    To facilitate the use of broad consent, the NPRM proposes that the 
Secretary of HHS will publish in the Federal Register templates for 
broad consent that would contain all of the required elements of 
consent in these situations. It is envisioned that there would be at 
least two broad consent templates developed: One for information and 
biospecimens originally collected in the research context, and another 
for information and biospecimens originally collected in the non-
research context.
    In addition, two exemptions are proposed related to facilitating 
secondary research use of biospecimens and identifiable private 
information when the Secretary's broad consent template is used. These 
exemptions are described in section II.A.3 of this preamble.
    The NPRM also proposes that the template for consent established by 
the Secretary may serve as the written consent form in circumstances 
when the proposed exemption categories at Sec.  __.104(f) require 
written consent. In circumstances where Sec.  __.104(f)(1) allows for 
oral consent, a subject's oral consent for secondary research use of 
identifiable private information must be documented such that the 
consent is associated with the subject's identifiable information. If 
this requirement is met through the use of written documentation, the 
subject would not be required to sign anything.
e. What would change?
     No change would be made in the current regulatory 
framework allowing research use of non-identified private information 
without consent, except that, when relevant, individuals would be given 
an option to consent or refuse to consent to the inclusion of their 
data, with the removal of certain identifiers, in a publicly available 
database.
     Broad consent would be permissible for the storage or 
maintenance for secondary research use of biospecimens and identifiable 
private information, and for the use of such stored material for 
individual research studies.
     No change would be made to the definition of ``legally 
authorized representative.''
f. Questions for Public Comment
    61. Public comment is sought on whether broad consent to secondary 
research use of information and biospecimens collected for non-research 
purposes should be permissible without a boundary, or whether there 
should be a time limitation or some other type of limitation on 
information and biospecimens collected in the future that could be 
included in the broad consent as proposed in the NPRM. If a time limit 
should be required, is the NPRM proposal of up to 10 years a reasonable 
limitation? Would a limitation related to an identified clinical 
encounter better inform individuals of the clinical information and 
biospecimens that would be covered by a broad consent document?
    62. Public comment is sought on whether all of the elements of 
consent proposed at Sec.  __.116(c) should be required for the 
secondary use of biospecimens or identifiable private information 
originally collected as part of a research study that was conducted 
without consent because either the original research study met an 
exclusion or exempt category of research, or a waiver of consent was 
approved by an IRB.
    63. Public comment is sought on whether oral consent should be 
permissible in limited circumstances as proposed under exemption Sec.  
__.104(f)(1).
    64. Would research subjects continue to be appropriately protected 
if the

[[Page 53975]]

definition of ``legally authorized representative'' were broadened to 
include individuals authorized by accepted common practice to consent 
on behalf of another individual to participation in clinical 
procedures? If the definition of ``legally authorized representative'' 
was broadened in this way, public comment is sought on the 
interpretation of ``accepted'' and ``common'' as these terms would be 
used in the revised definition.
3. Waiver of Informed Consent or Documentation of Informed Consent 
(NPRM at Sec. Sec.  __.116(e), (f) and __.117)
a. NPRM Goals
    The goals of the proposals related to the waiver of informed 
consent and the documentation of informed consent are to uphold 
individuals' autonomy interests in determining whether their 
biospecimens and identifiable private information may be used for 
secondary research, to facilitate the recruitment of prospective 
research subjects, and to create more flexible rules for documenting 
informed consent for certain subject populations.
b. Current Rule
    Currently the Common Rule permits an IRB to waive the requirements 
for obtaining informed consent under two sets of circumstances 
described at Sec.  __.116(c) or (d)). The most common set of 
circumstances requires that four specific criteria be satisfied (Sec.  
__.116(d)).
    Under the current Common Rule at Sec.  __.117(c), IRBs may waive 
the requirement for the investigator to obtain a signed consent form 
for some or all subjects. The current criteria for such a waiver may 
not be flexible enough for dealing with a variety of circumstances, 
such as when federally sponsored research is conducted in an 
international setting where for cultural or historical reasons signing 
documents may be viewed as offensive and problematic.
c. ANPRM Discussion
    The ANPRM asked whether changes to the regulations would clarify 
the current four criteria for waiver of informed consent and facilitate 
their consistent application. The ANPRM also asked for comments on the 
information investigators should be required to provide to prospective 
subjects in circumstances where the regulations would permit oral 
consent. Additional questions focused on whether there are additional 
circumstances under which it should be permissible to waive the usual 
requirements for obtaining or documenting informed consent, and whether 
there are types of research in which oral consent without documentation 
should not be permitted.
d. NPRM Proposals
    Many commentators have argued that these conditions for waiver of 
consent are vague and applied haphazardly at different 
institutions.59 60 In response to these concerns, SACHRP, 
through its Subcommittee on Subpart A, developed several 
recommendations regarding the interpretation of these waiver 
criteria.\61\ In particular, commenters have questioned the meaning of 
the criterion at Sec.  __.116(d)(2) that the waiver or alteration will 
not adversely affect the rights and welfare of the subjects. Questions 
have also been raised about the meaning of the term ``practicably'' as 
used in Sec.  __.116(d)(3), which states that the research could not 
practicably be carried out without the waiver or alteration.
---------------------------------------------------------------------------

    \59\ Green LA, Lowery JC, Kowalski CP, Wyszewianski L. Impact of 
institutional review board practice variation on observational 
health services research. Health Serv Res 2006;41:214-230.
    \60\ Sanders AB, Hiller K, Duldner J. Researchers' understanding 
of the federal guidelines for waiver of and exception from informed 
consent. Acad Emerg Med 2005;12:1045-1049.
    \61\ Secretary's Advisory Committee on Human Research 
Protections (2008, January 31). SACHRP Letter to HHS Secretary. 
Retrieved from Advisory Committee (SACHRP): http://www.hhs.gov/ohrp/sachrp/sachrpletter013108.html.
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    Further, some have argued that the requirements for obtaining 
waivers of informed consent or waivers of documentation of informed 
consent are confusing and inflexible, which leads to inconsistent 
application.\62\ These problems may not be inherent in the language of 
the Common Rule, but there may be some changes to the regulations or 
clarifications as to how to interpret and implement such regulations 
that could improve informed consent forms and the informed consent 
process.
---------------------------------------------------------------------------

    \62\ See supra note 59.
---------------------------------------------------------------------------

    The NPRM offers several proposals related to the waiver or 
alteration of informed consent provisions (Sec.  __.116(c) and (d) in 
the current rule, Sec.  __.116(e) and (f) in the NPRM). The NPRM 
proposes at Sec.  __.116(f)(1)(iv) to retain the language found in 
Sec.  __.116(d)(2) of the current Rule regarding the necessity to 
evaluate the rights and welfare of subjects before issuing a waiver of 
consent or altering consent procedures. Despite the vagueness of the 
term, IRBs should consider whether there are considerations distinct 
from the risk of harm and discomfort that the IRB should be able to 
take into account in deciding whether to approve a waiver or alteration 
of informed consent. Note that SACHRP's recommendations included a 
comment that the IRB should determine ``. . . that the waiver or 
alteration does not adversely impact the ethical nature or scientific 
rigor of the research. . . ,'' which implies that there could be 
ethical considerations other than the degree of risk that could 
legitimately affect the IRB's decision.
    This criterion can be interpreted to include rights conferred by 
pertinent federal law or regulation, relevant state or local law, the 
stipulations at Sec.  __.101(e) and (f) (in both the NPRM and the 
current Rule), or laws in other countries where research is to be 
conducted. It could also include considerations of privacy or the right 
to decide how someone is going to be treated, where the IRB determines 
that subjects have such a right that the waiver would adversely impact, 
or where the waiver would preclude them from obtaining a benefit they 
would otherwise receive. We recognize that further guidance regarding 
this criterion would be helpful.
    HHS has also evaluated the utility of the term ``practicably'' 
contained in the elements of waiver or alteration of consent (Sec.  
__.116(d)(3) in the current Rule). The NPRM proposes to keep this 
terminology at Sec.  __.116(f)(1)(ii) in the NPRM. SACHRP has noted 
that the commonly accepted definitions of the term ``practicably'' are 
(1) feasible; (2) capable of being effected, done or put into practice; 
and (3) that may be practiced or performed; capable of being done or 
accomplished with available means or resources. SACHRP emphasized this 
criterion states that the research could not practicably be carried out 
without the waiver or alteration. In other words, it would not be 
practicable to perform the research (as it has been defined in the 
protocol by its specific aims and objectives) if consent was required. 
Thus it is impracticable to perform the research, and not just 
impracticable to obtain consent. SACHRP also offered the following 
concepts to help an IRB determine whether the research could not be 
practicably carried out without the waiver of consent: (1) Scientific 
validity would be compromised if consent was required; (2) ethical 
concerns would be raised if consent were required; (3) there is a 
scientifically and ethically justifiable rationale why the research 
could not be conducted with a population from whom consent can be 
obtained; (4) practicability should not be determined

[[Page 53976]]

solely by considerations of convenience, cost, or speed.\63\
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    \63\ See Secretary's Advisory Committee on Human Research 
Protections (2008, January 31). SACHRP Letter to HHS Secretary. 
Retrieved from Advisory Committee (SACHRP): http://www.hhs.gov/ohrp/sachrp/sachrpletter013108.html.
---------------------------------------------------------------------------

    SACHRP's recommendations are consistent with OHRP's interpretation 
of this waiver criterion. Consideration was given to replacing the term 
practicably with another term such as feasibly, but HHS is uncertain 
whether such a change would improve the understanding of this 
criterion. Thus the NPRM proposes to retain this phrase.
    Few comments to the 2011 ANPRM were received on this topic although 
many commenters expressed support for clarifying the key terms through 
guidance or altering the criteria. In particular, most comments on this 
topic noted the confusion that IRBs face when trying to understand the 
meaning of the terms ``practicably'' and ``adversely affect the rights 
and welfare of subjects.'' Some commenters expressed the opinion that 
the waiver criterion concerning rights and welfare should be 
interpreted to include reference to rights conferred by other federal 
laws or regulations, state or local laws, or laws in other countries 
where research is to be conducted. Some comments reflected concerns 
about privacy or security. Several commenters also pointed to the need 
to consider community norms throughout the consent process, including 
its documentation.
    The NPRM proposes to add a new waiver criterion at Sec.  
__.116(f)(1)(iii), which would require that, for research involving 
access to or use of identifiable biospecimens or identifiable 
information, the research could not practicably be carried out without 
accessing or using identifiers. This criterion was modeled on the 
comparable criterion in the HIPAA Privacy Rule, which requires that the 
research could not practicably be conducted without access to and use 
of the protected health information. The principle embodied in this 
additional criterion is that non-identified information should be used 
whenever possible in order to respect subjects' interests in protecting 
the confidentiality of their data and biospecimens.
    Additional more stringent waiver conditions apply to research 
involving biospecimens, specifically that (1) there are compelling 
scientific reasons for the research use of the biospecimens; and (2) 
the research could not be conducted with other biospecimens for which 
informed consent was or could be obtained. Under this new, more 
stringent waiver standard, the circumstances in which a waiver could be 
granted by an IRB should be extremely rare.
    The Common Rule departments and agencies considered whether to 
require institutions or IRBs to report to OHRP when this waiver of 
consent for research involving the use of biospecimens was approved by 
an IRB. If such a reporting were required, it is envisioned that OHRP 
could use the information to consider whether the waiver provision was 
being implemented appropriately or whether regulatory changes might be 
needed (e.g., because such waivers were too frequently being granted). 
It is estimated that such a reporting requirement would constitute 
almost no burden to institutions, since the very premise behind the 
waiver provision is that such waivers should be extremely rare. It is 
also recognized that such a reporting requirement might deter IRBs from 
utilizing the waiver provision. The NPRM does not include a reporting 
requirement to OHRP when this waiver of consent is approved by an IRB, 
but public comments are requested on whether such a reporting 
requirement should be included in the final rule.
    The Common Rule departments and agencies also considered whether 
the NPRM should propose that a waiver of consent not be permissible for 
secondary research involving the use of biospecimens. The purpose of 
such a requirement would be to encourage investigators to seek broad 
consent for such research. This proposal was not included in the NPRM, 
but public comments are requested on whether such a prohibition to 
waive informed consent should be included in the final rule.
    In addition, the NPRM proposes that the Common Rule prohibit IRBs 
from waiving informed consent if individuals were asked and refused to 
provide broad consent to the storage and maintenance for secondary 
research use of biospecimens and identifiable private information. If a 
subject refused to provide broad consent, it is proposed that this 
refusal would need to be recorded by the investigator to better ensure 
that the subject's wishes would be honored.
    The proposal to not allow any waivers of consent by an IRB with 
regard to the secondary research use of identifiable private 
information if an individual was asked to consent to such use, and 
refused to consent, was thoroughly considered during the drafting of 
this document. On the one hand, a core initial motivation for this NPRM 
has been the recognition that we should not be imposing unnecessary 
burdens on low-risk research that is capable of producing important 
knowledge. Re-using data that has been generated for other purposes, 
when appropriate protections for privacy and confidentiality are in 
place, seems to fit within that category.
    Moreover, with society's growing abilities to rapidly generate 
massive data sets, and manipulate such data using cutting-edge 
algorithms, research using ``big data'' seems more important than ever. 
At the same time, however, it is recognized that if an individual is 
asked to provide consent and declines or refuses to do so, the 
individual's choice should be honored, except perhaps under only very 
rare circumstances that justify overriding an individual's autonomy 
interest.
    Most of the provisions in this NPRM regarding the research use of 
identifiable private information have led to the conclusion that, when 
there are appropriate privacy protections in place, the balance between 
respect for persons and beneficence should come out in favor of 
facilitating the research, including not requiring informed consent in 
many instances. In recognition of this circumstance, while the NPRM 
proposes new consent requirements related to biospecimens (justified 
primarily by the special autonomy interest of a person in controlling 
the research use of such biospecimens), it does not impose such consent 
requirements with regard to research use of a person's identifiable 
private information. Accordingly, in most respects, the current Rules--
which do allow such use without consent, provided that an IRB has 
reviewed the study and found that it meets the criteria for the waiver 
of consent--are retained with regard to the secondary research use of 
such information. For research involving the secondary use of 
identifiable private information, waivers of consent appear to 
currently be quite frequently given by IRBs, and represent a 
significant (and likely growing) portion of the research universe.
    Accordingly, even after the implementation of this NPRM, an 
individual will still generally not have the right to prevent secondary 
research taking place using their identifiable private information, in 
the event that an IRB approves a waiver of consent for such a study. 
(Indeed, this is only one of the circumstances in which the NPRM allows 
such research to take place without consent; the NPRM has actually 
expanded such circumstances through some of the exclusions and 
exemptions, based on the ethical analysis mentioned above.) The main 
alteration of this rule by the NPRM

[[Page 53977]]

would be in the circumstance described above: Where the individual 
happened to be asked to sign a broad consent regarding the use of that 
information, and they refused to do so. If that happened, an IRB would 
no longer be able to waive consent.
    This is a complicated issue, and as discussed below, comments are 
sought on various aspects of the proposal to allow for broad consent 
for secondary use of identifiable private information, including 
whether it is appropriate to include the limitation on an IRB's ability 
to waive consent where a person has been asked to sign a broad consent 
form, but refused.
    The NPRM also clarifies that waivers of informed consent and the 
waivers related to documenting informed consent might not be permitted 
for research subject to FDA regulation. For example, research conducted 
with a waiver of informed consent, or its documentation, may, if 
submitted in support of a marketing application to FDA, become subject 
to certain applicable informed consent requirements under 21 CFR part 
50.
    A provision has also been added at Sec.  __.116(g) in the NPRM to 
address concerns that the current regulations require an IRB to 
determine that informed consent can be waived under the current Sec.  
__.116(d) (Sec.  __.116 (e) and (f) in the NPRM) before investigators 
may record identifiable private information for the purpose of 
identifying and contacting prospective subjects for a research study. 
This requirement to waive informed consent is viewed as burdensome and 
unnecessary to protect subjects, and is not consistent with FDA's 
regulations, which do not require informed consent or a waiver of 
informed consent for such activities. This proposal in the NPRM is 
intended to address these concerns and to make the Common Rule 
consistent with the FDA's regulations by eliminating the requirement 
for the IRB to waive informed consent for these activities while 
explicitly assuring that the information will be protected.
    With regard to documentation requirements, the NPRM proposes to 
alter the language at Sec.  __.117(b)(1) to specify that the consent 
document should include only the language required by Sec.  __.116, 
with appendices included to cover any additional information. The goal 
here is to reduce the length and complexity of the document and to 
ensure that the elements of information essential to decision-making 
receive priority by appearing in the main document.
    In addition, the NPRM would make it explicit in the regulatory 
language at proposed Sec.  __.117(c)(1)(iii) that if the subjects are 
members of a distinct cultural group or community for whom signing 
documents is not the norm, so long as the research presents no more 
than minimal risk of harm to subjects and provided there is an 
appropriate alternative mechanism for documenting that informed consent 
was obtained, the requirement to obtain a signed consent form may be 
waived. Documentation must include a description as to why signing 
forms is not the norm for the distinct cultural group or community.
    Finally, as discussed above, to facilitate tracking of broad 
consent to storage or maintenance for secondary research use of 
biospecimens or identifiable private information, and to provide 
information to IRBs should IRB review be required, waiver of 
documentation of consent for the research use of such biospecimens 
would not be allowed based upon a new provision at Sec.  __.117(c)(3). 
The regulatory language proposed at Sec.  __.117(c)(4) would also 
clarify that waivers of documentation may not be permitted for research 
subject to regulation by FDA.
e. What would change?
     A new waiver criterion would be added at Sec.  
__.116(f)(1)(iii) requiring that, for research involving access to or 
use of biospecimens or identifiable information, the research could not 
practicably be carried out without accessing or using identifiers.
     Additional waiver criteria would apply to research 
involving the use of biospecimens.
     If a person was asked to provide broad consent to store or 
maintain for secondary research use biospecimens or identifiable 
private information and refused to do so, a waiver of consent would not 
be allowed with respect to the research use of such person's 
biospecimens or private identifiable information.
     A new provision would be added at Sec.  __.116(g) stating 
that an IRB may approve a research proposal in which investigators 
obtain identifiable private information without individuals' informed 
consent for the purpose of screening, recruiting, or determining the 
eligibility of prospective human subjects of research, through oral or 
written communication or by accessing records, in order to obtain 
informed consent, if the research proposal includes an assurance that 
the investigator will implement standards for protecting the 
information obtained in accordance with and to the extent required by 
Sec.  __.105.
     The language at Sec.  __.117(b)(1) would be altered to 
specify that the consent document should include only the language 
required by Sec.  __.116, with appendices included to cover any 
additional information. The goal here is to reduce the length and 
complexity of the document and to ensure that the elements of 
information essential to decision-making receive priority by appearing 
in the consent document.
     A new provision would be added at Sec.  __.117(c)(1)(iii) 
allowing a waiver of the requirement for a signed consent form if the 
subjects are members of a distinct cultural group or community for whom 
signing documents is not the norm. This would be allowed only if the 
research presents no more than minimal risk of harm to subjects and 
provided there is an appropriate alternative method for documenting 
that informed consent was obtained.
f. Questions for Public Comment
    65. Public comment is sought on how the waiver criterion regarding 
``practicably'' at Sec.  __.116(d)(3) could be explicitly defined or 
otherwise clarified (e.g., what term should replace ``practicably''?).
    66. Public comment is sought on the proposed differences between 
the criteria for waiving informed consent for the research use of 
biospecimens versus identifiable information.
    67. Public comment is sought on whether the proposal to permit an 
IRB to waive consent for research involving the use of biospecimens 
should be included in the regulations.
    68. Public comment is sought on the proposal to permit an IRB to 
waive consent for the secondary use of biospecimens or information 
originally collected for research purposes, even if the original 
research study required subjects' informed consent.
    69. Public comment is sought regarding how likely investigators are 
to seek broad consent for the use of identifiable private information 
(as contrasted with biospecimens), given that there are provisions 
within the NPRM that would make it easier to do such research without 
consent (such as the new exemption at Sec.  __.104(e)(2)). In this 
regard, note that the NPRM proposal to prohibit waiver of consent by an 
IRB if a person has been asked for broad consent and refused to provide 
it might create a disincentive on the part of investigators from 
choosing to seek broad consent for research involving secondary use of 
identifiable private information. Given the costs and time and effort 
involved in implementing the system for obtaining broad consent for the 
use of identifiable private

[[Page 53978]]

information and tracking when people provide consent or refuse to do 
so, are the benefits to the system likely to outweigh the costs, and if 
so, should the broad consent provisions be limited to obtaining broad 
consent for research use of biospecimens?
    70. Public comment is sought on the proposed prohibition on waiving 
consent when an individual has been asked to provide broad consent 
under Sec.  __.116(c) and refused. In particular, how would this 
prohibition on waiving consent affect the secondary research use of 
identifiable private information? If an individual was asked to provide 
such consent, should the absence of a signed secondary use consent be 
considered a refusal? Does this prohibition on waiving consent for the 
secondary use of identifiable private information create a disincentive 
for institutions to seek broad secondary use consent and instead seek a 
waiver of consent from an IRB? Under what circumstances, if any, would 
it be justified to permit an IRB to waive consent even if an individual 
declined or refused to consent?
4. Posting of Consent Forms
a. NPRM Goals
    Public posting of consent forms is intended to increase 
transparency, enhance confidence in the research enterprise, increase 
accountability, and inform the development of future consent forms.
b. NPRM Proposal
    Thus, the NPRM proposes a new provision at Sec.  __.116(h)(1) that 
would require that a copy of the final version of the consent form 
(absent any signatures) for each clinical trial conducted or supported 
by a Common Rule department or agency be posted on a publicly available 
federal Web site that will be established as a repository for such 
consent forms. The name of the protocol and contact information would 
be required to be included with the submission of the consent form. The 
primary purpose of this provision is to improve the quality of consent 
forms in federally funded research by assuring that--contrary to 
current practices, under which it is often very difficult to ever 
obtain a copy of these documents--they eventually would become subject 
to public scrutiny. It is anticipated that the Web site will be 
searchable.
    Under proposed Sec.  __.116(h)(2), the consent form must be 
published on the Web site within 60 days after the trial is closed for 
recruitment. By final consent form, it is anticipated that 
investigators generally will post the version of the consent form that 
had been most recently approved by an IRB. Note that even though a 
newer consent form could be developed after the timeframe specified 
here, investigators would only be required to post one consent form. 
Thus, even if a modification to a consent form occurs after it has been 
posted, investigators would not be required to re-post an updated 
document. Moreover, only one posting would be required for each multi-
site study. There is no expectation that a version would need to be 
posted for each study site.
    A Web site would be developed by HHS, which could be used by other 
Federal departments or agencies, or the other Federal departments or 
agencies could create their own Web sites for the posting of these 
consent forms.
c. What would change?
     A new provision at Sec.  __.116(h) would require that, for 
clinical trials conducted or supported by a Common Rule department or 
agency, a copy of the final version of a consent form would have to be 
posted on a publicly available federal Web site within 60 days after 
the trial is closed for recruitment.

C. Proposed Changes To Protect Information and Biospecimens (NPRM at 
Sec.  __.105)

1. NPRM Goal
    IRBs were not designed to evaluate risks to privacy and 
confidentiality, and often have little expertise in these matters. 
Setting uniform specific standards will help to assure appropriate 
privacy and confidentiality protections to all subjects, without the 
administrative burden of needing a specific committee review of the 
privacy and confidentiality protections of each study.
    Increasing research use of genetic information, information 
obtained from biospecimens, and the ability to more easily merge 
multiple sources of administrative and survey datasets (e.g., medical 
records, claims data, vital records, and information about lifestyle 
behaviors from surveys) have increased the stakes associated with data 
breaches. For example, the unauthorized release or use of information 
about subjects such as the disclosure of Social Security or Medicare 
numbers may pose financial risks, and disclosure of illegal behavior, 
substance abuse, or chronic illness might jeopardize subjects' current 
or future employment, or cause emotional or social harm. The risks of a 
large portion of social and behavioral research are also generally 
informational risks.
    The goal of the NPRM here is to create information privacy 
protections that would apply to research, calibrated to the level of 
identifiability and sensitivity of the information being collected.
2. Current Rule and Other Regulatory or Statutory Requirements
    Currently, the Common Rule at Sec.  __.111(a)(7) requires that IRBs 
evaluate each study with regard to all levels of risk and are expected 
to determine whether the privacy of subjects and the confidentiality of 
their information are protected. Under the Common Rule, IRBs must 
review each individual study's protection plan to determine whether it 
is adequate with respect to the informational risks of that study.
    In addition, the HIPAA Privacy Rule addresses some of these 
informational risks by imposing restrictions on how individually 
identifiable health information collected by health plans, health care 
clearinghouses, and most health care providers (``covered entities'') 
may be used and disclosed, including for research. In addition, the 
HIPAA Security Rule (45 CFR parts 160 and 164, Subparts A and C) 
requires that these entities implement certain administrative, 
physical, and technical safeguards to protect this information when in 
electronic form from unauthorized use or disclosure. However, the HIPAA 
Rules apply only to covered entities (and in certain respects to their 
business associates), and not all investigators are part of a covered 
entity. Moreover, the Privacy Rule does not apply specifically to 
biospecimens in and of themselves.
    Separate from the HIPAA Rules, the Privacy Act of 1974, as amended 
(5 U.S.C. 552a) requires Federal agencies to protect certain 
information in their possession and control. However, it does not apply 
to non-Federal investigators.
3. ANPRM Discussion
    The ANPRM suggested establishment of mandatory data security and 
information protection standards for all studies that involve the 
collection, generation, storage, or use of identifiable or potentially 
identifiable information that might exist electronically or in paper 
form or contained in a biospecimen. It put forward the idea that these 
standards might be modeled after certain standards of the HIPAA Rules 
and asked a series of questions about how best to protect private 
information.

[[Page 53979]]

4. NPRM Proposals
    Some public comments reflected confusion about the focus of the 
suggested standards and whether they would apply to information or 
biospecimens that were not individually identifiable. Although most 
commenters confirmed the need to protect the privacy and 
confidentiality of information of human subjects in research, a 
majority expressed serious concerns about the merits of requiring all 
investigators to meet standards modeled on certain HIPAA standards, 
such as those in the HIPAA Security Rule. Most commenters expressed the 
opinion that certain HIPAA standards are not well suited to some 
research of various kinds carried out by investigators not subject to 
the HIPAA Rules. Some commenters claimed that the HIPAA privacy 
safeguards do not adequately protect individuals' information. Many 
commenters claimed that standards modeled after certain HIPAA standards 
would be unnecessarily burdensome for studies in the behavioral and 
social sciences where the data are often less sensitive than health 
information.
    Some comments maintained that HIPAA-like standards would not always 
be suitable for the variety of research methods and procedures for the 
collection and storage of information in research activities not 
subject to the HIPAA Rules. Some commented that certain HIPAA standards 
would not be suitable because of the location of the research activity, 
or because the kind of institution supporting the research was 
significantly different from a covered entity. Others thought the HIPAA 
standards create confusion and complications for investigators and 
institutions that would increase if standards modeled on certain HIPAA 
standards were applied across the board. At the same time, regardless 
of the specific standards to be employed under this approach, several 
commenters noted that the additional administrative burden that might 
be created by establishing a data security and information protection 
system could be offset by the decreased time and attention IRBs would 
have to invest in reviewing every study that required data or 
biospecimen protections. They also noted that many institutions already 
have required data and biospecimen protection systems in place.
    Some commenters noted that expansion of some of the exemption 
categories could only be ethically acceptable if those research 
activities were subject to a requirement for data security and 
information protection, because information collected for some research 
studies would no longer be collected under a research plan approved by 
an IRB. With regard to an absolute prohibition against re-identifying 
de-identified data, many commenters expressed concern, and provided 
reasons why re-identification might be valid or even desirable, 
including the need to return clinically relevant research results to an 
individual. For example, if the research uncovers information that 
might have important clinical significance for an individual, re-
identification could be used so that the individual could get care. In 
addition, they pointed out that the current Common Rule requires 
investigators who re-identify non-identified private information as 
part of a research study to comply with the current Common Rule 
regulatory requirements.
    The NPRM proposes to require that investigators and institutions 
conducting research subject to the Common Rule implement reasonable 
safeguards for protecting against risks to the security or integrity of 
biospecimens or identifiable private information. Given the significant 
concerns of public commenters about the idea discussed in the ANPRM of 
adopting the standards solely modeled on certain standards of the HIPAA 
Rules, the NPRM proposes several sets of standards, and allows a choice 
about which to use. First, the NPRM proposes to have the Secretary of 
HHS publish a list of specific measures that an institution or 
investigator can use to meet the requirements. The list would be 
evaluated and amended, as appropriate, after consultation with other 
Common Rule departments and agencies. The proposed list will be 
published in the Federal Register, and public comment on the proposed 
list will be sought before the list is finalized.
    The list of specific safeguards that would be identified by the 
Secretary will be designed such that they could be readily implemented 
by the individual investigator, could build on existing safeguards 
already in place to protect research data, and would involve minimal 
cost and effort to implement. These standards would include security 
safeguards to assure that access to physical biospecimens or data is 
limited only to those who need access for research purposes. These 
standards would also assure that access to electronic information is 
only authorized for appropriate use. Finally, these safeguards would 
assure that information and biospecimens posing informational risks to 
subjects would be protected according to appropriate standards.
    Second, if an institution or investigator is currently required to 
comply with the HIPAA rules, then the safeguards required by the Common 
Rule would be satisfied. No additional requirements are proposed to 
protect information that is subject to the HIPAA Rules. The NPRM also 
proposes to clarify at Sec.  __.105(d) that the provisions at Sec.  
__.105 do not amend or repeal the requirements of 45 CFR parts 160 and 
164 for the institutions or investigators to which these regulations 
apply pursuant to 45 CFR 160.102. Institutions or investigators that 
are not required to follow HIPAA could voluntarily implement the HIPAA 
Rules and be considered to satisfy the Sec.  __.105 privacy protections 
requirements. For Federal departments and agencies that conduct 
research activities that are or will be maintained on information 
technology that is subject to and in compliance with section 208(b) of 
the E-Government Act of 2002, 44 U.S.C. 3501 note, if all of the 
information collected, used, or generated as part of the activity will 
be maintained in systems of records subject to the Privacy Act of 1974, 
5 U.S.C. 552a, and the research will involve a collection of 
information subject to the Paperwork Reduction Act of 1995, 44 U.S.C. 
3501 et seq., the requirements of Sec.  __.105 will be deemed 
satisfied.
    For the purposes of informing the development of the Sec.  __.105 
privacy safeguards, comment is sought on what types of safeguards would 
be appropriate.
    There are additional statutes or acts that mandate the protection 
of privacy and confidentiality of identifiable private information that 
may be reasonable to include in Sec.  __.105(b) as additional standards 
which, if research is already subject to those standards or a 
voluntarily election to comply with them is made, should perhaps be 
viewed as meeting the new requirement. These include:
     The Confidential Information Protection and Statistical 
Efficiency Act, 44 U.S.C. 3501 note;
     The Family Educational Rights and Privacy Act of 1974, 20 
U.S.C. 1232g;
     The Census Act, 13 U.S.C. 1 et seq.;
     Agency for Healthcare Research & Quality (AHRQ) statutory 
provision protecting the confidentiality of identifiable data obtained 
for research purposes by AHRQ or its contractors and grantees, 42 
U.S.C. 299c-3(c);
     The CDC National Center for Health Statistics (NCHS) 
statutory confidentiality provision at Section 308(d) of the Public 
Health Service Act,

[[Page 53980]]

42 U.S.C. 242m(d) (using nearly identical language to the AHRQ 
statutory provision referenced above);
     The Substance Abuse and Mental Health Services 
Administration authorizing statute regarding confidentiality of alcohol 
and drug abuse patient records at 42 U.S.C. 290dd-2;
     The Department of Justice statute related to 
confidentiality of information used by the Office of Justice Programs 
at 42 U.S.C. 3789g;
     The Department of Education statute related to Education 
Sciences Reform at 20 U.S.C. 9573.
    Public comment is sought on whether any of the above referenced 
statutes or acts would serve the goals of Sec.  __.105. Note that the 
statutes and acts referenced in Sec.  __.105(b) are currently 
referenced in the proposed exclusions at Sec.  __.101(b)(2)(i) 
(exclusion for surveys, educational tests, and public observation) and 
Sec.  __.101(b)(2)(iii) (exclusion for federal departments or agencies 
to use pre-existing federally generated non-research data). To that 
end, public comment is also sought as to whether the goals of the NPRM 
are served by referencing any of the aforementioned statutes, acts, or 
standards in the exclusions proposed in Sec.  __.101(b)(2)(i) and 
(iii).
    In order to reduce burden on IRBs that may under the current 
regulation be tasked with ensuring that safeguards are commensurate 
with informational risk, IRB review of required safeguards generally 
would not be required. Note that while the proposed language at Sec.  
__.111(a)(7) requires that IRBs consider if the privacy safeguards at 
Sec.  __.105 are sufficient to protect the privacy of subjects and the 
confidentiality of data, the presumption would be that these privacy 
safeguards are sufficient in most circumstances.
    The new section includes conditions for use and disclosure of 
research information to other entities, consistent with those 
protections to participants in research conducted by Federal employees 
and their contractors. It requires that protections be in place when 
biospecimens or identifiable private information are shared for 
appropriate research or other purposes as specified in the rule. Unless 
required by law, the NPRM would limit the re-disclosure of biospecimens 
and identifiable private information that were obtained for research 
purposes to the following four purposes: (1) For human subjects 
research regulated under the Common Rule; (2) for public health 
purposes; (3) for any lawful purpose with the consent of the subject; 
or (4) for other research purposes if the institution or investigator 
has obtained adequate assurances that: The recipient investigator will 
implement and maintain the level of safeguards required by this 
provision, and the research has been approved by an IRB under Sec.  
__.111 (except for human subjects research that qualifies for exclusion 
under proposed Sec.  __.101(b) or exemption under proposed Sec.  __.104 
and the recipient will not further disclose the biospecimens or 
identifiable private information except as permitted by this provision 
(NPRM at Sec.  __.105(c)).
    These four purposes are additional uses or disclosures of 
biospecimens or identifiable private information collected in research, 
because the subjects themselves consented, or because the information 
and biospecimens will continue to be safeguarded, or because the public 
health will be served. For the purposes of this requirement, an 
institution or investigator must obtain adequate assurances through the 
use of a written agreement with the recipient of the biospecimens or 
identifiable private information that the recipient will abide by these 
conditions. In developing this provision, Common Rule departments and 
agencies discussed whether it was appropriate to limit the re-
disclosure of biospecimens and identifiable private information 
``unless [such a disclosure was] required by law'' or if some other 
standard (such as ``unless [such a disclosure was] authorized by law'') 
would be appropriate. Public comment is sought on whether limiting re-
disclosure to four specific circumstances unless such a disclosure was 
``required by law'' is too restrictive, or whether more permissive 
standards would better facilitate the NPRM goal of fostering the 
secondary research use of information.
    Also, research involving the collection and use of biospecimens or 
identifiable private information that would qualify for an exemption 
under section Sec.  __.104(e) and (f) must conform to the privacy 
safeguards proposed in Sec.  __.105. A proposed change also appears at 
Sec.  __.115(c), requiring that IRB records that contain identifiable 
private information also be safeguarded through compliance with the 
safeguards proposed at Sec.  __.105.
    In addition to ensuring that biospecimens and identifiable private 
information are protected, a benefit of this new provision is that IRBs 
would not be required to review the individual plans for safeguarding 
information and biospecimens for each research study, so long as 
investigators will adhere to them. While there is a presumption that 
the proposed Sec.  __.105 privacy safeguards are sufficient, an IRB may 
determine that a particular activity requires more than what is 
discussed in Sec.  __.105. Once IRBs are familiar with standard 
institutional and investigator adopted protections, it is anticipated 
that they will become more comfortable with the fact that they need not 
review every protocol for privacy safeguards. In addition, there will 
be an overall reduction in regulatory burden because IRBs will not have 
to review security provisions on a case-by-case basis.
    Finally, the proposed exemptions found at Sec.  __.104(e) and (f), 
which will permit a larger number of protocols to proceed without IRB 
review if specific conditions are met, are conditioned on investigators 
and institutions meeting these privacy and security requirements. Note 
that there is currently no requirement for an IRB to determine whether 
investigators are adhering to the Sec.  __.105 privacy safeguards for 
research exempted under Sec.  __.104(e) or (f).
5. What would change?
     The NPRM would create a set of standards for the 
protection of information for research to create an effective and 
efficient means of implementing appropriate protections for information 
and biospecimens.
     The NPRM also proposes to include limitations for the use 
and disclosure of information and biospecimens.
     IRBs would be required to safeguard their records in 
compliance with the provisions at Sec.  __.105 if the records contain 
identifiable private information.
6. Questions for Public Comment
    71. Public comment is sought regarding whether particular 
information security measures should be required for certain types of 
information or research activities and, if so, what measures and for 
what types of information or research. Specifically, should the 
safeguards be calibrated to the sensitivity of the information to be 
collected?
    72. Are the proposed limitations on re-disclosure more or less 
restrictive than necessary? Are there additional purposes for which re-
disclosure of biospecimens or identifiable private information should 
be permitted?

D. Harmonization of Agency Guidance (NPRM at Sec.  __.101(j))

1. NPRM Goal
    From the outset of the development of the Common Rule, the 
importance of consistency across the Federal Government has been 
recognized. Each

[[Page 53981]]

Common Rule department or agency may issue its own guidance regarding 
the protection of human subjects. Consequently, there may be variations 
in the guidance issued.
    As the label of the Common Rule suggests, there seems to be a 
compelling case for consistency across Federal departments and agencies 
regarding guidance on the protections of human subjects. Nevertheless, 
there are arguments in favor of some departments or agencies imposing 
specific requirements, apart from the Common Rule, that are tailored to 
certain types of research. The various agencies that oversee the 
protection of human subjects range from regulatory agencies, to those 
agencies and departments that conduct research, and to those that 
support and sponsor research. In addition, in some cases, statutory 
differences among the agencies have resulted in different regulatory 
requirements and agency guidance. Not only do the agencies have 
different relationships to the research, but they also oversee very 
different types and phases of research and thus there may be reasonable 
justifications for differences in guidance. Moreover, achieving 
consensus across the entire Federal Government may be arduous, 
preventing timely issuance of guidance.
2. Current Rule
    Each Common Rule agency, and the FDA, is authorized to issue its 
own guidance with regard to interpreting and implementing the 
regulations protecting human subjects. That guidance may substantially 
differ from agency to agency.
    Currently, there are multiple efforts to address variation in 
guidance across the Federal Government, but there is no regulatory 
requirement for agencies to consult other departments prior to issuance 
of a policy, to the extent appropriate. As a result, inter-departmental 
communication is at times uneven, leading to potentially avoidable 
inconsistencies. The Common Rule departments and agencies have 
procedures for sharing proposed guidance before it is adopted, and 
these procedures have generally been successful. Additionally, FDA and 
OHRP have been working closely to ensure harmonization of guidance and 
regulation to the extent possible, given the differing statutory 
authorities and regulatory missions.
3. ANPRM Discussion
    The ANPRM did not suggest any specific approaches to harmonization 
but asked for public comment on a set of questions focused on: (1) The 
extent to which differences in guidance on research protections from 
different agencies strengthen or weaken protections for human subjects; 
(2) the extent to which differences in guidance on research protections 
from different agencies facilitate or inhibit the conduct of research 
domestically and internationally; and (3) the desirability of all 
Common Rule agencies issuing one set of guidance.
4. NPRM Proposal
    Responses to questions in the 2011 ANPRM about the need for 
harmonization across Common Rule agencies reflected widespread support 
for such efforts. Several commenters acknowledged the difficulty of 
getting all Common Rule agencies to agree on all issues, as each has a 
different mission and research portfolio. However, they encouraged 
seeking harmonized guidance whenever possible.
    Thus, the NPRM proposes that the regulations contain language at 
Sec.  __.101(j) requiring consultation among the Common Rule agencies 
for the purpose of harmonization of guidance, to the extent 
appropriate, before federal guidance on the Common Rule is issued, 
unless such consultation is not feasible.
    The Department believes this proposal appropriately recognizes the 
importance of harmonized guidance by creating an expectation that 
guidance should only be issued after consultation among the Common Rule 
agencies, while also permitting guidance to be issued without such 
consultation when it is not feasible. The proposal also recognizes that 
harmonization will not always be possible or desirable given the varied 
missions of the agencies that oversee the protection of human subjects 
and differences in statutory authorities. Although the NPRM proposal is 
limited to requiring consultation for the purpose of harmonization, the 
Common Rule agencies may wish to consult with one another before 
issuing guidance for reasons other than the purpose of harmonization, 
and the proposal would not preclude this. Some concerns have been 
expressed that the proposed language in Sec.  __.101(j) does not go far 
enough to mandate harmonization in guidance between Common Rule 
agencies. Others are concerned that this provision would, in effect, 
mean that Common Rule agencies issue fewer guidance documents because 
of lengthy internal government review and approval processes. Public 
comment is sought about the effectiveness of the consultation language 
proposed in Sec.  __.101(j), and whether this language should require 
more (or less) than consultation amongst Common Rule agencies before 
guidance is issued.
    For example, FDA intends to modify its regulations in light of this 
NPRM, to the extent appropriate, considering its unique statutory 
framework and regulatory mission. In developing guidance that 
interprets its human subject protection regulations that mirror the 
requirements found in the Common Rule, FDA may seek consultation with 
the Common Rule agencies, to the extent feasible. Further, FDA and OHRP 
will continue to work together in developing guidance on their 
respective regulatory requirements that are found both in FDA 
regulations and in the Common Rule, to the extent feasible.
5. What would change?
     The regulations would contain language at Sec.  __.101(j) 
requiring consultation among the Common Rule agencies for the purpose 
of harmonization of guidance, to the extent appropriate, before federal 
guidance on the Common Rule is issued, unless such consultation is not 
feasible.
6. Question for Public Comment
    73. Will the proposed language at Sec.  __.101(j) be effective in 
achieving greater harmonization of agency guidance, and if not, how 
should it be modified?

E. Cooperative Research (NPRM and Current Rule at Sec.  __.114) and 
Proposal To Cover Unaffiliated IRBs Not Operated by an Institution 
Holding a Federalwide Assurance (NPRM at Sec.  __.101(a))

1. NPRM Goal
    The goal is to enhance and streamline the review process, reduce 
inefficiencies, and hold unaffiliated IRBs directly accountable for 
regulatory compliance, without compromising ethical principles and 
protections.
2. Current Rule
    Currently, an institution engaged in non-exempt human subjects 
research conducted or supported by any Federal department or agency 
that has adopted the Common Rule is required to hold an OHRP-approved 
FWA or another assurance of compliance approved by the Federal 
department or agency conducting or supporting the research. The FWA 
mandates the application of the Common Rule only to certain federally 
funded research projects. Most institutions voluntarily extend the 
applicability of the Common Rule to all the research conducted at their

[[Page 53982]]

institutions, even research not conducted or supported by one of the 
federal departments or agencies that have adopted the Common Rule.\64\ 
However, such extensions are not required. Many observers have called 
for legislation that would extend the Common Rule protections to all 
research with human subjects conducted in the United States, regardless 
of funding source.
---------------------------------------------------------------------------

    \64\ According to the OHRP's FWA Database, twenty-five percent 
of institutions with an active FWA have formally extended the Common 
Rule to all research conducted at those institutions, regardless of 
funding source (by ``checking the box'' on their assurance). 
Comments from the regulated community suggest that most 
institutions, however, voluntarily follow the requirements of the 
Common Rule in all research activities conducted at these 
institutions.
---------------------------------------------------------------------------

    In addition, IRBs not affiliated with an institution holding an FWA 
are not directly subject to oversight for compliance through the 
vehicle of the FWA. OHRP's current practice of enforcing compliance 
with the Common Rule in situations where an institution relies on an 
external IRB is through the institutions that are engaged in human 
subjects research, even in circumstances when the regulatory violation 
is directly related to the responsibilities of an external IRB. Thus, 
certain aspects of the regulations are not directly applied to external 
IRBs.
    External IRB review of cooperative research may be problematic 
given the current lack of direct regulatory accountability and the 
large volume of cooperative reviews. The inefficiencies of multiple IRB 
reviews for cooperative studies adds bureaucratic complexity to the 
review process, and delays initiation of research projects without 
evidence that multiple reviews provide additional protections to 
subjects.
    The Common Rule currently requires that each institution engaged in 
a cooperative research study obtain IRB approval of the study, although 
it does not require that a separate local IRB at each institution 
conduct such review. In many cases, however, a local IRB for each 
institution does independently review the research protocol, informed 
consent forms and other materials, sometimes resulting in hundreds of 
reviews for one study. When any one of these IRBs requires changes to 
the research protocol that are adopted for the entire study, 
investigators must re-submit the revised protocol to all of the 
reviewing IRBs. This process can take many months and can significantly 
delay the initiation of research projects and recruitment of subjects 
into studies.
    In 2006, the FDA issued guidance intended to assist sponsors, 
institutions, IRBs, and clinical investigators by facilitating the use 
of a centralized IRB review process in cooperative clinical trials of 
investigational new drugs.\65\
---------------------------------------------------------------------------

    \65\ See FDA Guidance at: Guidance for Industry: Using a 
Centralized IRB Review Process in Multicenter Clinical Trials. 
(2006, March). Retrieved from U.S. Food and Drug Administration: 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127013.pdf.
---------------------------------------------------------------------------

    Currently, the choice to have cooperative research reviewed by a 
central IRB, or by an IRB at another institution, is voluntary under 
the Common Rule. In practice, most institutions have been reluctant to 
replace review by their local IRBs with review by a central IRB.
3. Relevant Prior Proposals and Discussions
    The choice to have cooperative research reviewed by a single 
unaffiliated IRB (or by an external IRB operated by or affiliated with 
another FWA-holding institution) currently is voluntary. In practice, 
most institutions have been reluctant to replace review by their local 
IRBs with review by a single IRB. Participants in two meetings on 
alternative IRB models co-sponsored by OHRP in November 2005 and 
November 2006 indicated that one of the key factors influencing 
institutions' decisions about this issue is OHRP's current practice of 
enforcing compliance with the Common Rule through the institutions that 
were engaged in human subjects research,\66\ even in circumstances when 
the regulatory violation is directly related to the responsibilities of 
an external IRB.
---------------------------------------------------------------------------

    \66\ In general, an institution is considered engaged in a 
particular non-exempt human subjects research project when its 
employees or agents for the purposes of the research project obtain: 
(1) Data about the subjects of the research through intervention or 
interaction with them; (2) identifiable private information about 
the subjects of the research; or (3) the informed consent of human 
subjects for the research. Office for Human Research Protections. 
(2008, October 16). Guidance on Engagement of Institutions in Human 
Subjects Research. Retrieved from Policy & Guidance: http://www.hhs.gov/ohrp/policy/engage08.htmll.
---------------------------------------------------------------------------

    In 2009, OHRP issued an ANPRM in the Federal Register requesting 
information and comments from the public about whether the office 
should pursue a notice of proposed rulemaking to enable OHRP to hold 
IRBs and the institutions or organizations operating the IRBs directly 
accountable for meeting certain regulatory requirements of the Common 
Rule.\67\ OHRP contemplated this regulatory change to encourage 
institutions to rely on IRBs that are operated by another institution 
or organization, when appropriate. In this ANPRM, OHRP stated that it 
believed that such a regulatory change in its enforcement authority 
might address one of the main disincentives institutions have cited as 
inhibiting them from exercising the regulatory flexibility that 
currently permits institutions to implement a variety of cooperative 
review arrangements and to rely on the review of an IRB operated by 
another institution or organization. If institutions become more 
willing to rely on cooperative review arrangements and on review of 
IRBs operated by other institutions or organizations, this could reduce 
administrative burdens associated with implementing the Common Rule 
without diminishing human subject protections.
---------------------------------------------------------------------------

    \67\ 74 FR 9568 (Mar. 5, 2009).
---------------------------------------------------------------------------

    The ANPRM sought public comment on the feasibility, advantages, and 
disadvantages of mandating that all domestic (United States) sites in a 
study involving more than one institution rely on a single IRB for that 
study. This would apply regardless of whether the study underwent 
convened review or expedited review. Further, it would only affect 
which IRB would be designated as the reviewing IRB for institutional 
compliance with the IRB review requirements of the Common Rule. It 
would not relieve any site of its other obligations under the 
regulations to protect human subjects. Nor would it prohibit 
institutions from choosing, for their own purposes, to conduct 
additional internal ethics reviews, though such reviews would no longer 
have any regulatory status in terms of compliance with the Common Rule.
    Based on public comments received to the 2009 ANPRM \68\ on the 
issue of IRB accountability and to address institutions' concerns about 
OHRP's practice of enforcing compliance with the Common Rule through 
the institutions that are engaged in human subjects research, the 2011 
ANRPM also suggested that appropriate accompanying changes could be 
made in enforcement procedures to hold external IRBs directly 
accountable for compliance with certain regulatory requirements.\69\ 
This change was discussed only for United States sites in multi-
institutional studies. The ANPRM suggested that, in most cases, 
independent local IRB reviews of international sites are appropriate 
because it might be difficult for an IRB in the U.S. to adequately 
evaluate local conditions in a foreign country that could play an 
important role in the ethical evaluation of the study.
---------------------------------------------------------------------------

    \68\ 74 FR 9578 (Mar. 5, 2009).
    \69\ 74 FR 9578 (Mar. 5, 2009). Also available at http://www.hhs.gov/ohrp/newsroom/rfc/com030509.html.

---------------------------------------------------------------------------

[[Page 53983]]

    In late 2014, NIH issued a Request for Comments on the Draft NIH 
Policy on the Use of a Single Institutional Review Board for Multisite 
Research. The response to NIH's proposed policy was robust and largely 
supportive, with many institutions citing both reduced duplication of 
effort and faster initiation of research as important factors. A 
minority, however, pointed to the importance of maintaining independent 
local IRB review, and expressed doubt over the anticipated efficiencies 
and cost savings that would be incurred through a centralized model. 
SACHRP commented on this draft policy, and was generally supportive of 
voluntary increased use of a single IRB for multi-site studies, as such 
use may decrease differences among site implementation of protocols. 
SACHRP concluded that a uniform mandate of single IRB review for all 
domestic multi-site studies was premature, and recommended a more 
incentivized approach at this time.\70\
---------------------------------------------------------------------------

    \70\ Secretary's Advisory Committee on Human Research 
Protections. (2015). Recommendations Regarding the Draft NIH Policy 
on the Use of a Single Institutional Review Board for Multi-site 
Research. Retrieved from Office for Human Research Protections: 
http://www.hhs.gov/ohrp/sachrp/commsec/useofasingle_irb.html.
---------------------------------------------------------------------------

4. NPRM Proposals
    These issues attracted a large number of comments to the 2011 
ANPRM, and revealed nearly evenly divided perspectives. Investigators 
and disease advocacy groups tended to favor the single IRB review 
requirement. IRB and institutional representatives tended to be opposed 
to the possible requirement, though many indicated single IRB review 
should be encouraged. Support was especially strong for single IRB 
review for cooperative clinical trials for which the evaluation of a 
study's social value, scientific validity, and risks and benefits, and 
the adequacy of the informed consent form and process generally do not 
require the unique perspective of a local IRB. Moreover, depending on 
the nature of the study, FDA may not permit differences in protocols 
across sites, which further bolstered commenters' views that the 
requirements be harmonized across the Common Rule and FDA requirements. 
Commenters reported incidences of IRBs continuously second-guessing 
each other, which delayed studies to the point that subject recruitment 
opportunities were foregone or lost. This problem seemed especially 
critical in studies of rare diseases and cancers, which nearly always 
involve multiple research sites.
    Support for the use of a single IRB, however, was not restricted to 
clinical trials. Several commenters cited long delays and burdensome 
requirements resulting from multiple reviews of studies in the 
behavioral and social sciences. In addition to the view that these 
administrative requirements do not enhance protections, supporters of a 
single IRB review of cooperative studies cited the frequent need for 
maintaining consistency across sites, which can be degraded by multiple 
reviews.
    Despite support for the ANPRM suggestion, several commenters 
expressed concern about making such a provision mandatory, stating that 
the current regulations at Sec.  __.114 permit the use of joint review 
arrangements for cooperative research. They noted that although this 
option exists, institutions might be hesitant to use it because of 
liability concerns and the unwillingness of institutions or IRBs to 
rely on the judgment of other institutions or IRBs. However, several 
commenters expressed concern about signaling the acceptability of a 
single IRB for review while allowing institutions to continue to 
conduct their own ethics review, fearing that such a policy would not 
correct the current situation, which tends to favor multiple reviews. 
Thus, they commented that mandating a single IRB might be the only way 
to achieve the goals of streamlining review while ensuring protections.
    Another issue raised was the need to set clearer expectations of 
the responsibilities of local IRBs that are not designated as the 
central IRB. A number of commenters supporting the requirement for a 
central IRB also requested that OHRP issue guidance on how to select 
the IRB, responsibilities of all parties, and compliance and 
enforcement policies. Several commenters also requested that OHRP 
develop a template for reliance agreements to replace inter-
institutional agreements currently in use.
    Those who expressed concern about the use of a single IRB said some 
studies, especially in the behavioral and social sciences, might 
involve significant contextual issues reflecting community norms, 
standards, and practices, or local culture and customs. Use of a 
distant IRB might not consider and best protect subjects based on 
community norms. Others noted that such concerns can be addressed by 
investigators or IRBs submitting ``points to consider'' regarding 
significant contextual or cultural considerations of relevance to their 
site.
    A primary issue posed by those opposed to mandating use of a single 
IRB in cooperative studies focused on potential loss of accountability 
and increased liability for the institutions where the research is 
conducted but where the reviewing IRB is not located.
    Taking into consideration this public debate and various sources of 
public comments, the NPRM proposes a requirement at Sec.  __.114(b)(1) 
mandating that all institutions located in the United States engaged in 
cooperative research rely on a single IRB as their reviewing IRB for 
that study. Under proposed Sec.  __.114(b)(2), this requirement would 
not apply to: (1) Cooperative research for which more than single IRB 
review is required by law (e.g., FDA-regulated devices); or (2) 
research for which the Federal department or agency supporting or 
conducting the research determines and documents that the use of a 
single IRB is not appropriate for the particular study.
    Based on comments to OHRP's 2011 ANPRM, the NPRM also proposes to 
add a new provision at Sec.  __.101(a) that would explicitly give 
Common Rule departments and agencies the authority to enforce 
compliance directly against unaffiliated IRBs that are not operated by 
an assured institution. This change is proposed to address concerns 
about OHRP's current practice of enforcing compliance with the Common 
Rule through the institutions that are engaged in human subjects 
research, even in circumstances when the regulatory violation is 
directly related to the responsibilities of an external IRB. In large 
part, this change was made to facilitate the use of a single IRB in 
cooperative research, allowing OHRP to enforce compliance with the 
Common Rule through non-compliant external IRBs rather than the 
institutions that were engaged in human subjects research. This 
proposal should encourage institutions to be more willing to rely on a 
single IRB for cooperative research as required under the NPRM proposal 
at Sec.  __.114. It would reassure institutions using an external IRB 
because compliance actions could be taken directly against the IRB 
responsible for the flawed review, rather than the institutions that 
relied on that review.
    Some public commenters responding to the 2011 ANPRM cautioned that 
extending compliance oversight to external IRBs might serve as a 
disincentive for some IRBs to be the IRB of record for cooperative 
research. A majority of commenters expressed an opposing view; that is, 
holding external IRBs directly accountable for compliance with the 
regulations would increase the comfort level of institutions in 
accepting the regulatory review of an external IRB.

[[Page 53984]]

    Related to this issue is a new provision proposed at Sec.  
__.103(e) regarding policies for documenting an institution's reliance 
on an external IRB. That provision states that for non-exempt research 
involving human subjects covered by this policy that takes place at an 
institution in which IRB oversight is conducted by an IRB that is not 
affiliated with the institution, the institution and the IRB should 
establish and follow written procedures identifying the compliance 
responsibilities of each entity. These procedures should be set forth 
in an agreement between the institution and the IRB specifying the 
responsibilities of each entity in ensuring compliance with the 
requirements of this policy.
    This would only apply to U.S.-conducted portions of studies because 
the flexibility to make use of external local IRB reviews of 
international sites should be maintained; it might be difficult for an 
IRB in the United States to adequately evaluate local conditions in a 
foreign country that could play an important role in the ethical 
evaluation of the study.
    This policy would apply regardless of whether the study underwent 
convened review or expedited review. This proposal only affects the 
decision regarding how an IRB would be designated as the reviewing IRB 
for institutional compliance with the IRB review requirements of the 
Common Rule. The reviewing IRB is expected to be selected either by the 
funding agency or, if there is no funding agency, by the lead 
institution conducting the study. An agency may solicit input regarding 
which IRB would be most appropriate to designate as the IRB of record. 
Public comment is sought on how this will work in practice.
    This policy would not relieve any site of its other obligations 
under the regulations to protect human subjects. Nor would it prohibit 
institutions from choosing, for their own purposes, to conduct 
additional internal IRB reviews, though such reviews would no longer 
have any regulatory status in terms of compliance with the Common Rule. 
Although a local IRB may conduct its own additional internal review, 
such a review would not be binding on the local site if not adopted by 
the single IRB, and the terms of it would not be enforced by OHRP.
    Relevant local contextual issues (e.g., investigator competence, 
site suitability) pertinent to most studies can be addressed through 
mechanisms other than local IRB review. For research where local 
perspectives might be distinctly important (e.g., in relation to 
certain kinds of vulnerable populations targeted for recruitment), 
local IRB review could be limited to such consideration(s); but again, 
IRB review is not the only mechanism for addressing such issues. The 
evaluation of a study's social value, scientific validity, and risks 
and benefits, and the adequacy of the informed consent form and process 
generally do not require the unique perspective of a local IRB.
    The proposal also modifies the current regulations by removing the 
requirement that only with the approval of the department or agency 
head may an institution participating in a cooperative project enter 
into a joint review arrangement, rely upon the review of another IRB, 
or make similar arrangements for avoiding duplication of effort. Such 
approval is no longer required.
    Some detractors of mandated single IRB review for cooperative 
research point to concerns regarding implementation logistics, and the 
time necessary to establish new policies, procedures, and agreements; 
recognizing this concern, the proposed compliance date is three years 
from the publication of the final rule.
5. What would change?
     IRBs not affiliated with an assured institution that 
review research covered by the Common Rule would be subject to direct 
compliance oversight regarding IRB regulatory requirements.
     All U.S. institutions engaged in a cooperative study would 
rely upon a single IRB for that study, with some exceptions.
6. Questions for Public Comment
    74. Is mandated single IRB review for all cooperative research a 
realistic option at this time? Please provide information about the 
likely costs and benefits to institutions. Will additional resources be 
necessary to meet this requirement in the short term? Should savings be 
anticipated in the long run?
    75. What areas of guidance would be needed for institutions to 
comply with this requirement? Is there something that OHRP could do to 
address concerns about institutional liability, such as the development 
of model written agreements?
    76. Would it be useful for this requirement to include criteria 
that Federal departments or agencies would need to apply in determining 
whether to make exceptions to the use of a single IRB requirement? If 
so, what should these criteria be?
    77. Are the exceptions proposed appropriate and sufficient, or 
should there be additional exceptions to this mandate for single IRB 
review than those proposed in the NPRM? If additional exceptions should 
be included, please provide a justification for each additional 
exception recommended.
    78. Is three years appropriate timing to establish compliance with 
this provision?

F. Changes To Promote Effectiveness and Efficiency in IRB Operations

1. Continuing Review of Research (NPRM at Sec.  __.109(f); Current Rule 
at Sec.  __.109(e))
a. NPRM Goal
    The goal is to reduce or eliminate the need for continuing review 
in specific circumstances, thereby reducing regulatory burden that does 
not meaningfully enhance protection of subjects.
b. Current Rule
    The current regulations at Sec.  __.109(e) require that IRBs 
conduct continuing review of research covered by this policy at 
intervals appropriate to the degree of risk, but not less than once per 
year. Except when an expedited review procedure is used, continuing 
review of research must occur at convened meetings at which a majority 
of the IRB members are present, including at least one member whose 
primary concerns are in nonscientific areas. In order for research 
undergoing continuing review to be approved, it must receive the 
approval of a majority of those members present at the meeting (Sec.  
__.108(b)).
    An IRB may use an expedited review procedure to conduct continuing 
review of research for some or all of the research appearing on the 
list of research eligible for expedited review \71\ and found by the 
reviewer(s) to involve no more than minimal risk. OHRP may restrict, 
suspend, terminate, or choose not to authorize an IRB's use of the 
expedited review procedure (Sec.  __.110(d)).
---------------------------------------------------------------------------

    \71\ See Office for Human Research Protections (OHRP)--
Categories of Research That May Be Reviewed by the Institutional 
Review Board (IRB) through an Expedited Review Procedure. November 
9, 1998, http://www.hhs.gov/ohrp/policy/expedited98.html.
---------------------------------------------------------------------------

c. ANPRM Discussion
    The ANPRM requested comments on eliminating continuing review for 
all minimal risk studies that undergo expedited review, unless the 
reviewer explicitly justifies why continuing review would enhance 
protection of research subjects. For studies initially reviewed by a 
convened IRB, continuing review would not be required, unless

[[Page 53985]]

specifically mandated by the IRB, after the study reaches the stage 
where procedures are limited to either (1) analyzing data (even if it 
is identifiable), or (2) accessing follow-up clinical data from 
procedures that subjects would undergo as part of standard care for 
their medical condition or disease.
d. NPRM Proposals
    The NPRM proposes at Sec.  __.109(f) eliminating continuing review 
for many minimal risk studies (namely those that qualify for expedited 
review), unless the reviewer documents why continuing review should 
take place (as would be required by Sec.  __.115(a)(8)). Moreover, for 
studies initially reviewed by a convened IRB, continuing review would 
not be required, unless specifically mandated by the IRB, after the 
study reaches the stage where it involves one or both of the following: 
(1) Analyzing data (even if it is identifiable private information), or 
(2) accessing follow-up clinical data from procedures that subjects 
would undergo as part of standard care for their medical condition or 
disease.
    In addition, continuing review would not be required for research 
involving certain secondary research using information and biospecimens 
that requires limited IRB review in order to qualify for exemption 
under Sec.  __.104(f)(1).
    Further, the NPRM proposes at Sec.  __.109(f)(2) that an IRB must 
receive annual confirmation that such research is ongoing and that no 
changes have been made that would require the IRB to conduct continuing 
review (that is, the study still qualifies for expedited review because 
it still meets the criteria listed above and still involves no greater 
than minimal risk). This confirmation allows the IRB to 
administratively account for research that is occurring without 
continuing review. Investigators would continue to be required to 
submit changes to the protocol to the IRB. This requirement aims to 
address concerns some might have about institutional liability relating 
to the status of ongoing research, the possibility for increased 
noncompliance among investigators no longer required to ``check in,'' 
and possible breakdowns in lines of communications between 
investigators and IRBs. Institutions will have significant flexibility 
in how they implement this requirement. For example, some might rely on 
an automated electronic communication with the investigator at one-year 
intervals after the study was initiated that might merely require the 
investigator to type ``yes'' indicating that the study is ongoing and 
that no changes have been made. It is therefore anticipated that this 
requirement can be met with minimal time and effort on the part of 
investigators and IRBs. Investigators would still have the current 
obligations to report various developments (such as unanticipated 
problems or proposed changes to the study) to the IRB.
    If an IRB chooses to conduct continuing review even when these 
conditions are met, the rationale for doing so must be documented 
according to a new provision at Sec.  __.115(a)(8).
    The NPRM, at Sec.  __.115(a)(3), proposes a new requirement for 
IRBs to maintain records of continuing reviews. Because the NPRM 
proposes a new provision that eliminates the need for continuing review 
under specific circumstances (Sec.  __.109(f)(1)), the NPRM at Sec.  
__.115(a)(8) also proposes that IRBs need to justify the need for 
continuing review in cases where they will not follow the provision in 
Sec.  __.109(f)(1).
e. What would change?
     Continuing review would be eliminated for all studies that 
undergo expedited review, unless the reviewer explicitly justifies why 
continuing review would enhance protection of research subjects. For 
studies initially reviewed by a convened IRB, once certain specified 
procedures are all that remain for the study, continuing review would 
not be required, unless specifically mandated by the IRB. However, 
investigators would be required to provide annual confirmation to the 
IRB that such research is ongoing and that no changes have been made 
that would require the IRB to conduct continuing review.
     Continuing review would not be required for research 
involving certain secondary research using information and biospecimens 
that requires limited IRB review in order to qualify for exemption 
under Sec.  __.104(f)(1).
2. Expedited Review Procedures and the Definition of ``Minimal Risk'' 
(NPRM at Sec. Sec.  __.110 and __.102(j))
a. NPRM Goal
    IRBs report challenges in assessing the level of risk presented by 
some studies in order to make the critical minimal risk determination. 
This is, in part, due to the difficulties in applying the current 
definition of minimal risk within the Common Rule, particularly because 
the terms ``ordinarily encountered in daily life'' and ``routine 
physical or psychological examinations'' are not clarified. The goal is 
to help eliminate this ambiguity as it pertains to expedited review, 
and improve the efficiency and consistency of minimal risk 
determinations for some activities.
b. Current Rule
    The concept of ``minimal risk'' is central to numerous aspects of 
the Common Rule, the determination of which affects the type of review 
required, considerations for IRBs in the review process, and the 
frequency of review. In sum, the review process has been calibrated, 
for the most part, to the risk of the research.
    The current definition of minimal risk at Sec.  __.102(i) 
encompasses research activities where ``the probability and magnitude 
of harm or discomfort anticipated in the research are not greater in 
and of themselves than those ordinarily encountered in daily life or 
during the performance of routine physical or psychological 
examinations or tests.''
    Under the Common Rule at Sec.  __.110, a research study can receive 
expedited review if the research activities to be conducted appear on 
the list of activities published by the Secretary of HHS that are 
eligible for such review,\72\ and is found by the reviewer(s) to 
involve no more than minimal risk. Under an expedited review procedure, 
the review may be carried out by the IRB chairperson or by one or more 
experienced reviewers designated by the chairperson from among the 
members of the IRB. Research that is eligible for expedited review 
requires continuing review at least annually.
---------------------------------------------------------------------------

    \72\ See Office for Human Research Protections (OHRP)--
Categories of Research That May Be Reviewed by the Institutional 
Review Board (IRB) through an Expedited Review Procedure. November 
9, 1998, http://www.hhs.gov/ohrp/policy/expedited98.html.
---------------------------------------------------------------------------

c. ANPRM Discussion
    The ANPRM suggested updating the current list of research 
activities eligible for expedited review; this list was last updated in 
1998. It also considered mandating that a federal panel periodically 
(such as every year or every two years) review and update the list, 
based on a systematic, empirical assessment of the levels of risk. This 
would provide greater clarity about what would be considered to 
constitute minimal risk, and create a process that allows for routinely 
reassessing and updating the list of research activities that would 
qualify as minimal risk. The ANPRM asked for public comments on 
categories of research that should be considered for addition to the 
current list.

[[Page 53986]]

    The ANPRM asked for public comment on whether the current 
regulatory definition of minimal risk is appropriate. The ANPRM further 
suggested that the ``default'' assumption would be that a study 
otherwise eligible for expedited review will be considered minimal risk 
unless a reviewer documents the rationale for classifying the study as 
involving more than minimal risk.
    Finally, the ANPRM discussed the idea that continuing review would 
not be required of studies that are eligible for expedited review 
unless the reviewer, at the time of initial review, determines that 
continuing review is required, and documents why. In follow-up to this 
discussion, the ANPRM asked for comments on whether IRBs should be 
required to report instances when they overrode the default presumption 
that research appearing on the posted list did not warrant review by a 
convened IRB.
d. NPRM Proposal
    Based on public comments on the ANPRM, the NPRM proposes changes to 
the current regulatory language at Sec.  __.110(b)(1) regarding 
expedited review, and will allow expedited review to occur for studies 
on the Secretary's list unless the reviewer(s) determine(s) that the 
study involves more than minimal risk. This is in contrast to the 
current regulations, which require that an IRB use the expedited review 
procedure only if the reviewer determines that the research involves no 
more than minimal risk; in addition, OHRP has indicated that the 
activities on the current list should not be deemed to be of minimal 
risk simply because they are included on the list. Therefore, this 
proposed change represents a change to the default position, and now 
says that research included on the list only involves minimal risk, 
unless the IRB makes a determination that the research is actually 
greater than minimal risk. Thus, it is anticipated that more studies 
that involve no more than minimal risk would undergo expedited review, 
rather than full review, which would relieve burden on IRBs.
    This proposal is in line with public comment to the 2011 ANPRM. 
Commenters overwhelmingly welcomed the clarification that categories of 
research found on the published list should be presumed to be minimal 
risk. However, commenters were largely opposed to requiring IRBs to 
report instances when they conducted a review by the convened 
membership (versus an expedited review) for studies appearing on the 
list. They were opposed because of the additional administrative burden 
and also because they felt such a requirement would undermine the 
purview of local review and open IRBs up to second-guessing by OHRP.
    Public comments to the 2011 ANPRM expressed both a desire to retain 
the current definition (slightly less than half) and a desire for 
changing it (slightly more than half). There were few common themes in 
the suggested changes to the language other than seeking clarification 
on what baselines an IRB should consider in determining the meaning of 
``daily life'' and ``routine physical or psychological examinations.'' 
Several commenters acknowledged the difficulty of arriving at a concise 
definition for all circumstances. Those opposed to changing the 
definition said that IRBs generally understand how to interpret the 
language and that difficult or challenging application of the 
definition will persist regardless of the definition for those areas of 
research where risks are difficult to assess. Commenters recognized 
that the risks encountered in daily life can vary greatly depending on 
many factors, for example, where people live, what kind of work they 
are involved in, what their social and economic environment is, and 
their baseline health status. Thus, IRBs need to consider all of these 
issues in making a determination about the level of risk.
    Thus, the NPRM does not propose to modify the definition of minimal 
risk (NPRM at Sec.  __.102(j)), but rather proposes adding to the 
definition a requirement that the Secretary of HHS create and publish a 
list of activities that qualify as ``minimal risk.'' This Secretary's 
list will be re-evaluated periodically, but at least every 8 years, 
based on recommendations from federal departments and agencies and the 
public. Note that this will not be an exhaustive list of all activities 
that should be considered minimal risk under the Common Rule, but will 
allow IRBs to rely on the determination of minimal risk for activities 
appearing on the list. IRBs will still need to make minimal risk 
determinations about activities that do not appear on this list.
    In addition, the NPRM proposes to eliminate the parenthetical 
phrase ``of one year or less'' at Sec.  __.110(b)(2) since annual 
continuing review of research eligible for expedited review and 
research that progresses to the point of only involving specified 
limited activities will no longer be required for all ongoing human 
subjects research. The NPRM also proposes that the regulations be 
revised at Sec.  __.110(a) to require evaluation of the list of 
expedited review categories every 8 years, followed by publication in 
the Federal Register and solicitation of public comment. A revised list 
will be prepared for public comment outside the scope of the NPRM.
    For several reasons, the NPRM proposes no changes in the 
requirement that expedited review be conducted by an IRB member. First, 
public comments on the 2011 ANPRM were divided on the value of allowing 
a non-IRB member to conduct such reviews. Those with concerns 
questioned whether permitting someone other than an IRB member to 
conduct expedited review would have unintended consequences, such as 
either increasing or decreasing the number of studies deemed acceptable 
for expedited review, or by increasing liabilities for the institution. 
Second, IRB staff members would likely constitute the pool of non-IRB 
members qualified to conduct expedited review, and the current 
regulations permit IRB staff members to be IRB members. HHS does not 
believe a regulatory change is warranted to facilitate expedited 
review.
    Finally, the NPRM contains a requirement at Sec.  __.115(a)(9) that 
IRBs document the rationale for an expedited reviewer's determination 
that research appearing on the expedited review list is more than 
minimal risk (i.e., an override of the presumption that studies on the 
Secretary's list are minimal risk). Such documentation could provide a 
basis for the Secretary's future determinations about the 
appropriateness of the list, and allow for greater internal consistency 
at institutions. In response to public comment on the 2011 ANPRM, the 
NPRM does not propose to require that institutions report such 
determinations directly to OHRP. Commenters were largely opposed to 
requiring IRBs to report instances when they conducted a review by the 
convened membership (versus an expedited review) for studies appearing 
on the list. They were opposed because of the additional administrative 
burden and also because they felt such a requirement would undermine 
the purview of local review and open IRBs up to second-guessing by 
OHRP.
e. What would change?
     Expedited review can occur for studies on the Secretary's 
list unless the reviewer(s) determine(s) that the study involves more 
than minimal risk.
     Evaluation of the list of expedited review categories 
would occur every 8 years, followed by publication in the Federal 
Register and solicitation of public comment.
     IRBs will be required to document their rationale when 
they override the presumption that studies on the

[[Page 53987]]

Secretary's expedited review list involve greater than minimal risk.
     The Secretary of HHS will create and publish and maintain 
a list of activities that should be considered minimal risk.
f. Questions for Public Comment
    79. How often should the Secretary's list of minimal risk 
activities be updated? Should advice be solicited from outside parties 
when updating the list?
    80. Is this Secretarial list of minimal research activities a 
useful tool for the research community, or does it represent a loss of 
IRB flexibility in risk determination?

G. Proposed Changes to IRB Operational Requirements

1. Proposed Criteria for IRB Approval of Research (NPRM at Sec.  
__.111)
a. NPRM Goals
    These revisions modernize the rule by (1) creating new forms of IRB 
review for activities relating to storing or maintaining data and 
biospecimens for later secondary use, and for the review of studies 
involving certain types of such secondary use; (2) revising two of the 
existing criteria for approval of research, where there are special 
considerations related to the involvement of vulnerable populations and 
for privacy and confidentiality of data provisions; and (3) adding a 
provision regarding plans to review the return of individual results to 
participants.
b. Current Rule
    There are several determinations that an IRB must generally make 
before it can approve a study, which are spelled out in current Common 
Rule at Sec.  __.111. These relate, among other things, to minimizing 
risks to subjects, determining that there is an appropriate 
relationship between risks and benefits, and assuring the equitable 
selection of subjects. The regulations generally require all of these 
determinations to be made with regard to any study that must undergo 
IRB review.
c. ANPRM Discussion
    The ANPRM asked whether all of the Sec.  __.111 criteria should 
still be required for approval of studies that qualify for expedited 
review, and if not, which ones should not be required. Currently, 
before an IRB may approve a research study, including research that is 
being reviewed under an expedited procedure, the IRB must find that the 
criteria at Sec.  __.111 have been met.
d. NPRM Proposals
    Based on comment to the 2011 ANPRM, the NPRM does not propose to 
modify the Sec.  __.111 criteria that apply to research reviewed under 
the expedited procedure versus research reviewed under full board 
review. The NPRM does however propose a number of changes regarding the 
criteria for IRB approval of research, including (1) creating a new 
form of IRB review for activities relating to storing or maintaining 
data and biospecimens for later secondary use; (2) revising two of the 
existing criteria for approval of research, where there are special 
considerations related to the involvement of vulnerable populations and 
for privacy and confidentiality of data provisions; and (3) adding a 
provision regarding plans to review the return of individual results to 
participants.
    The first set of changes relates to updating the IRB review 
criteria for research activities relating to storing or maintaining 
information and biospecimens, and to the secondary use of such 
information and biospecimens. Paragraph (a)(9)(i) of proposed Sec.  
__.111 would apply to storage or maintenance for secondary research use 
of biospecimens or identifiable private information. This provision 
would eliminate the need for an IRB to make the usual determinations 
with regard to such an activity. Instead, the IRB would be required to 
determine that the procedures for obtaining broad consent to the 
storage or maintenance of the biospecimens or information were 
appropriate, and met the standards included in the introductory 
paragraph of Sec.  __.116. In addition, if these storage and 
maintenance activities involved a change for research purposes from the 
way the biospecimens or information had been stored or maintained, then 
the IRB would have to determine that the biospecimen and privacy 
safeguards at Sec.  __.105 are satisfied for the creation of any 
related storage database or repository. Note that in many instances 
there will be no such change. For example, an individual could sign a 
consent form allowing broad unspecified future research use of 
information contained in their medical records, and that information 
would remain where it is, but be tagged in some manner to indicate that 
the individual has provided such consent.
    This in effect means that the default for such secondary research 
studies using either biospecimens or identifiable information will be 
that the initial broad consent would be sufficient, and that there will 
be no need to obtain a new consent from individuals for each specific 
research study that is conducted with the biospecimens and information.
    The second proposal, relating to vulnerable subjects, is intended 
to address an inconsistency in the current regulations among three 
provisions in the current Common Rule that address requirements related 
to the consideration of vulnerable populations: Sec. Sec.  __.107(a), 
__.111(a)(3), and __.111(b). Under the current Rule, only Sec.  
__.111(b) of these three provisions provides that vulnerability to 
coercion or undue influence is the type of vulnerability that should be 
considered. It is proposed that the criterion at Sec.  __.111(a)(3) be 
revised to align with the language of Sec.  __.111(b) to reflect that 
the vulnerability of the populations in these research studies should 
be considered to be a function of the possibility of coercion or undue 
influence, and that this vulnerability alone should be the IRB focus of 
concern with respect to this criterion. The proposed change is intended 
to provide greater consistency and clarity in IRB consideration of 
vulnerability of subject populations in research activities and 
appropriate protections. A comparable change is also proposed at Sec.  
__.107(a), pertaining to IRB membership. In addition, of these same 
three provisions in the current Rule, only Sec.  __.107(a) identifies 
``handicapped'' individuals (which the NPRM proposes be changed to 
``physically disabled'' individuals as discussed below in section 
II.G.2.c. of the preamble) as a vulnerable category of subjects. 
Therefore, to enhance consistency and clarity among these three 
provisions, it is proposed that the term ``physically disabled'' be 
inserted at Sec.  __.111(a)(3) and (b). This would mean that physically 
disabled persons would be among the individuals that the IRB may 
consider in determining that the selection of subjects is equitable 
(Sec.  __.111(a)(3)), and that the IRB may consider to be vulnerable to 
coercion or undue influence (Sec.  __.111(b)). Public comment is being 
sought on these proposed changes to the provisions related to 
vulnerable populations. Since it is proposed that the only 
vulnerability that needs to be considered is vulnerability to coercion 
or undue influence, and not other types of vulnerability, it is 
appropriate to review the subject populations to determine whether all 
of these subject populations identified in these three provisions 
should be considered vulnerable to coercion or undue influence. In 
particular, public comment is sought

[[Page 53988]]

about whether pregnant women and those with physical disabilities 
should be characterized as vulnerable to coercion or undue influence. 
Whether or not these subpopulations are considered vulnerable to 
coercion or undue influence would not affect the applicability of 
subpart B.
    The third proposed change would be an addition of paragraph (a)(8) 
to Sec.  __.111 clarifying that if an investigator submits as part of 
the protocol a plan for returning individual research results, the IRB 
will evaluate the appropriateness of the plan. IRBs need not determine 
whether there should be a plan for returning individual research 
results. Although many IRBs probably already review plans for return of 
results, many studies do not include this feature. Challenges can arise 
regarding return of individual research results when it is not clear if 
the findings have clinical validity or utility, or when the knowledge 
imparted may cause psychological distress or social harm. These issues 
have been the subject of frequent discussion, particularly regarding 
the Clinical Laboratory Improvement Amendments of 1988, 42 U.S.C. 
263a.\73\ \74\ \75\
---------------------------------------------------------------------------

    \73\ Presidential Commission for the Study of Bioethical Issues. 
(2013, December). Anticipate and communicate: Ethical management of 
incidental and secondary findings in the clinical, research, and 
direct-to-consumer contexts. Retrieved from Presidential Commission 
for the Study of Bioethical Issues: http://bioethics.gov/sites/default/files/FINALAnticipateCommunicate_PCSBI_0.pdf.
    \74\ Wolf SM et al. Managing incidental findings in human 
subjects research: Analysis and recommendations. J Law Med Ethics 
2008 Summer; 36(2):219-248, 211.
    \75\ Ofri D. 2013. Medicine's problem of `incidental findings.' 
Atlantic Monthly.
---------------------------------------------------------------------------

    An additional change is related to the proposed changes at Sec.  
__.105, and would clarify that it is not an IRB responsibility to 
review the security plans for biospecimens and identifiable private 
information for every protocol (i.e., on a case-by-case basis). It is 
assumed that once institutions and investigators have established 
policies and procedures for compliance with the new privacy safeguards 
at Sec.  __.105 (and it is expected that many already have already such 
procedures in place), that IRBs will be confident in omitting that 
aspect of their review of research, as it does not pose unusual privacy 
or security risks to subjects. It is proposed that this requirement 
will be modified to recognize that the requirements at Sec.  __.105 
will apply to all non-excluded research (unless the criteria for 
exemptions are met). The default position should be that if the privacy 
safeguards at Sec.  __.105 are being met, there is no need for 
additional IRB review of a research study's privacy and security 
protections. However, there might be extraordinary cases in which an 
IRB determines that privacy safeguards above and beyond those called 
for in Sec.  __.105 are necessary. Therefore, it is proposed that IRBs 
will be responsible for ensuring there are adequate provisions to 
protect the privacy of subjects and to maintain the security of data 
only if the IRB determines that the protections required in Sec.  
__.105 are insufficient.
e. What would change?
     A new version of more limited IRB approval criteria would 
be created for activities relating to the storage or maintenance of 
biospecimens and identifiable private information for the purposes of 
later doing secondary research with them.
     IRBs considering the Sec.  __.111(a)(3) approval criterion 
regarding equitable selection of subjects would need to focus on issues 
related to coercion or undue influence in research with vulnerable 
populations and not other considerations related to vulnerability.
     Physically disabled persons would be among the individuals 
that the IRB may consider in determining that the selection of subjects 
is equitable (Sec.  __.111(a)(3)), and that the IRB may consider to be 
vulnerable to coercion or undue influence (Sec.  __.111(b)).
     IRBs would need to consider the requirements for 
investigators to protect information, and biospecimens as a criterion 
for approval of research only if they find the protections under Sec.  
__.105 are not sufficiently protective.
     If a plan for returning research results is included as 
part of a protocol, IRBs would be required to determine whether the 
plan is appropriate. IRBs would not be required to determine whether 
such a plan is needed.
f. Questions for Public Comment
    81. What should IRBs consider when reviewing the plans for 
returning research results, for example, what ethical, scientific, or 
clinical concerns?
    82. Is the Sec.  __.111(a)(3) and (b) focus on issues related to 
coercion or undue influence in research with vulnerable populations, 
and not other considerations related to vulnerability, appropriate? 
Note that this focus also appears in proposed Sec.  __.107(a).
    83. Should pregnant women and those with physical disabilities be 
included in the category of subpopulations that may be vulnerable to 
coercion or undue influence?
2. Proposed Revisions to IRB Operations, Functions, and Membership 
Requirements
a. NPRM Goal
    The goal is to improve IRB operations and make relevant sections 
consistent with other areas of the NPRM.
b. Current Rule
    The current Rule outlines IRB functions and operations at 
Sec. Sec.  __.108 and __.103, and membership requirements at Sec.  
__.107.
c. NPRM Proposals
    The NPRM contains several proposals for changes in IRB operations, 
functions, and membership requirements. First, the requirements for 
recordkeeping by IRBs no longer appear in Sec.  __.103 of the rule. 
They are now described in Sec.  __.108(a)(2), (3), and (4).
    Also as previously discussed, IRBs would be required to safeguard 
their records in compliance with the privacy protections described in 
proposed Sec.  __.105 if the records contain individually identifiable 
information.
    Finally, there are four changes to the IRB membership requirements 
at Sec.  __.107(a). The first change is the elimination of the 
requirement that IRBs not consist entirely of individuals of one gender 
or profession. This provision is unnecessary, because the requirement 
that IRB membership reflect members of varying backgrounds and 
diversity, including gender, will accomplish the same effect. The 
deletion of this provision in the NPRM is not intended to alter the 
composition of IRBs from what had been established in the current Rule.
    For the reasons discussed above in section II.G.1.d, three 
additional changes are proposed to Sec.  __.107(a). It is proposed that 
Sec.  __.107(a) be modified so that consideration of vulnerability of a 
subject population would be limited to vulnerability to coercion or 
undue influence. This proposed change is consistent with the proposal 
at Sec.  __.111(a)(3). The proposed change is intended to result in 
greater consistency and clarity in IRB consideration of vulnerability 
of subject populations in research activities and appropriate 
protections.
    The third change in Sec.  __.107(a) is the insertion of 
``economically or educationally disadvantaged persons'' as an example 
of a vulnerable population, requiring an IRB to give consideration to 
membership expertise in this area. This language is already included in 
the current Rule at Sec.  __.111(a)(3) and Sec.  __.111(b). Adding this 
category of individuals to

[[Page 53989]]

those who may be considered vulnerable to coercion or undue influence 
at Sec.  __.107(a) is intended to create greater consistency among 
these three provisions.
    In order to modernize the regulatory language, the fourth change in 
proposed Sec.  __.107(a) is the replacement of the term ``handicapped'' 
persons with ``physically disabled persons'' as an example of a 
vulnerable population, requiring an IRB to give consideration to 
membership expertise in this area.
d. What would change?
     The provision regarding IRBs avoiding membership that 
consists entirely of individuals of one gender or profession would be 
eliminated because the requirement that IRB membership reflect members 
of varying backgrounds and diversity, including gender, would 
accomplish the same goal.
     The provision regarding the IRB's expertise in the review 
of research involving a vulnerable category of subjects would be 
limited to the subjects' vulnerability to coercion or undue influence
     The phrase economically or educationally disadvantaged 
persons is included as an example of a vulnerable category of subjects, 
requiring an IRB to give consideration to membership expertise in this 
area.
     The term ``handicapped'' persons is replaced with 
``physically disabled persons'' as an example of a vulnerable category 
of subjects, requiring an IRB to give consideration to membership 
expertise in this area.
e. Question for Public Comment
    84. Should populations be considered vulnerable for reasons other 
than vulnerability to coercion or undue influence? Are the proposed 
categories appropriate?

H. Other Proposed Changes

1. Proposal To Extend the Common Rule to All Clinical Trials (With 
Exceptions) (NPRM at Sec.  __.101(a)(1))
a. NPRM Goals
    The goal of this proposal is to ensure that studies that generally 
pose the most risk to potential subjects (such as surgical clinical 
trials), are encapsulated by the Common Rule. The proposal attempts to 
balance the goals of ensuring that studies where the Common Rule 
provides meaningful protections to subjects are covered under the rule, 
while studies where the administrative burdens of the Common Rule 
outweigh any potential benefits to subjects are not covered.
b. Current Rule
    The Common Rule applies to all research involving human subjects 
that is conducted or supported by a Federal department or agency that 
has adopted the policy (Sec.  __.101(a)).
c. ANPRM Discussion
    The ANPRM discussed the possibility of the Common Rule applying to 
all studies, regardless of funding source, that are conducted by a U.S. 
institution that receives some federal funding for human subjects 
research from a Common Rule agency.
    The ANPRM also asked the public to consider a regulatory option to 
partially fulfill the goal of extending Common Rule protections to all 
human subjects research in the United States. The discussed policy 
would require domestic institutions that receive some federal funding 
from a Common Rule agency for non-exempt research with human subjects 
to extend the Common Rule protections to all human subjects research 
studies conducted at their institution.
d. NPRM Proposal
    In response to ANPRM feedback, the Common Rule NPRM proposes an 
extension that would ensure that clinical trials are covered by the 
Common Rule if conducted at an institution in the United States that 
receives federal support for non-exempt and non-excluded human subjects 
research, regardless of the funding source of the specific clinical 
trial.
    Note that the purpose of the clinical trials extension is to ensure 
that clinical trials that would otherwise not be covered by some body 
of federal research ethics regulations are covered. To that end, if a 
clinical trial is already subject to FDA oversight but not Common Rule 
oversight, since that clinical trial is subject to human subjects 
protection regulations, this change would not affect it. Also note that 
this proposed extension is based on whether an institution receives 
funding specifically for non-exempt and non-excluded research. This is 
because the Common Rule departments and agencies have a more 
substantial relationship with institutions that receive support from a 
Common Rule department or agency to conduct non-exempt and non-excluded 
human subjects research than those institutions that receive such 
support for only exempt and excluded human subjects research.
    Although supporting the principle that all human subjects research 
regardless of funding source should be conducted ethically, public 
commenters generally expressed concern and caution about the ANPRM 
consideration for a variety of reasons. Behavioral and social science 
investigators thought that this approach would unnecessarily bring 
less-than-minimal-risk research funded by non-federal sources (e.g., 
surveys or observational studies supported by the nonprofit sector) 
under burdensome regulatory requirements while not enhancing 
protections. Some commenters argued that the increased regulatory 
burden that would ensue was not warranted and would shift scarce 
oversight resources to review of research studies that are generally 
non-problematic and frequently supported by non-federal funds, such as 
some student or institutional research.
    Others argued that such a change was an overreach of federal 
oversight and constituted an unfunded mandate. Commenters from large 
academic research institutions felt that this change inappropriately 
focused heavily on academic institutions, which generally extend 
protections to all human subjects research at their institution, even 
if they have not ``checked the box'' \76\ on their FWA indicating that 
they do so. They argued that such a change would not reach those 
institutions already operating outside the federal research system and 
would limit flexibility in making risk-based determinations about the 
levels of review required.
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    \76\ The FWA covers all non-exempt human subjects research at 
the submitting institution that is conducted or supported by HHS, or 
funded by any other federal department or agency that has adopted 
the Common Rule and relies upon the FWA. It is not project specific. 
Domestic institutions may voluntarily extend their FWA (and thus a 
Common Rule department or agency's regulatory authority) to cover 
all human subjects research at the submitting institution regardless 
of the source of support for the particular research activity. See 
Office for Human Research Protections. (2011, June 17). What 
research does the Federalwide Assurance (FWA) cover? Retrieved from 
Frequently Asked Questions: http://www.hhs.gov/ohrp/policy/faq/assurance-process/what-research-does-fwa-cover.html.
---------------------------------------------------------------------------

    Industry also expressed concern about having to comply with two 
sets of regulations, that is, FDA regulations as well as the Common 
Rule. The ANPRM did not clarify that the changes under consideration 
would not require compliance with the Common Rule of non-federally 
funded research subject to regulation by FDA. However, there might 
continue to be research that would be subject to both sets of 
regulations involving federal funding of research concerning an FDA-
regulated product.

[[Page 53990]]

    Those commenters who supported a formal extension of the 
regulations cited the need to have one set of standards for all 
research, regardless of funding source; however, many noted that absent 
legislation covering all human subjects research conducted in the 
United States, it would be difficult to cover all research through a 
regulatory approach alone--gaps would still remain.
    Thus, the NPRM proposes changes in the regulatory language at Sec.  
__.101(a)(2) to state that the policy extends to all clinical trials as 
defined by this policy, irrespective of funding source, that meet all 
of three conditions: (1) The clinical trials are conducted at an 
institution that receives support from a federal department or agency 
for human subjects research that is not excluded from this policy under 
Sec.  __.101(b)(2), and the research does not qualify for exemption in 
accordance with Sec.  __.104; (2) The clinical trials are not subject 
to FDA regulation; and (3) The clinical trials are conducted at an 
institution located within the United States.
    For purposes of this policy, the NPRM proposes at Sec.  __.102(b) 
that a clinical trial be a research study in which one or more human 
subjects are prospectively assigned to one or more interventions (which 
may include placebo or other control) to evaluate the effects of the 
interventions on biomedical or behavioral health-related outcomes. By 
the term ``behavioral outcomes,'' the NPRM contemplates the reality 
that clinical trials may occur outside of the biomedical context. The 
studies addressed in the proposed definition of clinical trial at Sec.  
__.102(b) are more likely to involve greater-than-minimal risk, and, 
therefore, require the highest level of oversight. Limiting the 
extension of the regulations to only the highest risk research is 
consistent with the goal of a more risk-based approach to review. For 
example, surgical clinical trials that do not receive support from a 
Common Rule department or agency often are outside of the scope of 
FDA's human subjects protection regulations. Thus, many of these 
unfunded activities are currently not subject to the protections 
afforded by the human subjects protection system. This NPRM proposal 
would cause many of these trials to come under the purview of the 
Common Rule.
e. What would change?
     Clinical trials as defined by proposed Sec.  __.102(b), 
irrespective of funding source, would be subject to oversight, given 
specified conditions.
f. Questions for Public Comment
    85. Public comment is sought on whether there might be unintended 
consequences from the clinical trials expansion proposed in the NPRM in 
Sec.  __.101(a)(2)(i)). Unintended consequences may include an increase 
in burden or costs, or an inappropriate redistribution of costs.
    86. Public comment is sought as to whether the criterion that the 
policy extends to all clinical trials conducted at an institution that 
receives federal support (see the NPRM at Sec.  __.101(a)(2)(i)) should 
be further clarified in some way. For example, should it specify a 
timeframe for support (e.g., within the past number of years), or a 
minimum monetary threshold value?
    87. Public comment is sought on whether the definition of clinical 
trial (NPRM at Sec.  __.102(b)) should include additional explanation 
of what is encompassed by the term behavioral health-related outcomes.
2. Changes to the Assurance Process (NPRM at Sec. Sec.  __.103 and 
__.108; Current Rule at Sec.  __.103)
a. NPRM Goal
    There has been concern expressed by some, such as SACHRP, that the 
current assurance process may be unduly burdensome for institutions and 
does not provide meaningful protections for human subjects. The changes 
proposed to the assurance process are intended to reduce unnecessary 
administrative burdens.
b. Current Rule
    Requirements at Sec.  __.103 delineate procedural requirements for 
institutions and IRBs to follow to comply with the Common Rule.
c. NPRM Proposals
    A number of substantive and procedural modifications are proposed 
to Sec.  __.103 of the Common Rule. The NPRM proposes to move the IRB 
recordkeeping requirements from Sec.  __.103(b)(4) and (5) of the 
Common Rule. They are now described in the NPRM in Sec.  __.108(a)(3) 
and (4), which pertains to IRB functions and operations
    Additionally, the NPRM proposes to eliminate the current Common 
Rule requirement at Sec.  __.103(b)(1) that an institution provide a 
statement of ethical principles with which an institution will abide as 
part of the assurance process. This change was made because this 
provision is generally not enforced. Further, for international 
institutions that may receive U.S. government funding for research 
activities, it creates the impression that these international 
institutions must modify their internal procedures to comport with the 
set of principles designated on the FWA for activities conducted at 
those institutions that receive no U.S. government funding. OHRP 
specifically has received many questions about the extent to which 
international institutions must adhere to the ethical principles 
designated as part of the assurance process in research activities 
conducted by the institution that receive no Common Rule department or 
agency funding. In order to provide clarity to these international 
institutions that such measures are not required, the NPRM proposes to 
delete the requirement at Sec.  __.103(b)(1).
    The NPRM also proposes to eliminate the requirement in Sec.  
__.103(b)(2) that an institution designate one or more IRBs on its FWA 
established in accordance with the Common Rule. The requirement in the 
current Common Rule at Sec.  __.103(b)(2) that IRBs have sufficient 
meeting space and staff to support IRB reviews and recordkeeping 
requirements is found in the NPRM at Sec.  __.108(a)(1). Note that 
federal departments or agencies retain the ability to ask for 
information about which IRBs review research conducted at an 
institution as part of the assurance process, even if that requirement 
is not explicitly mandated in the regulations.
    Additionally, the NPRM proposes to eliminate the current 
requirement in Sec.  __.103(b)(3) that an up-to-date list of the IRB 
members and their qualifications be included in an institution's 
assurance. Instead, proposed Sec. Sec.  __.108(a)(2) and __.115(a)(5) 
require that an IRB or the institution prepare and maintain a current 
list of IRB members. This modification also eliminates the current 
requirement in Sec.  __.103(b)(3) that changes in IRB membership be 
reported to the department or agency head or to OHRP when the existence 
of an assurance approved by HHS for federalwide use is accepted. SACHRP 
recommended on March 28, 2008, that OHRP pursue harmonizing the Common 
Rule with FDA's human subjects protection regulations by eliminating 
the requirement to submit IRB membership lists. SACHRP members felt 
that submitting IRB membership lists and reporting all changes in IRB 
membership to OHRP added little to the protection of human subjects and 
that eliminating these requirements therefore would reduce unnecessary

[[Page 53991]]

administrative burdens on institutions and OHRP.\77\
---------------------------------------------------------------------------

    \77\ Secretary's Advisory Committee on Human Research 
Protections. (2008, September 18). SACHRP Letter to HHS Secretary. 
Retrieved from Office for Human Research Protections: http://www.hhs.gov/ohrp/sachrp/sachrpletter091808.html.
---------------------------------------------------------------------------

    Note that in implementing the NPRM an additional, non-regulatory 
change is planned to the assurance mechanism. The current option of 
``checking the box'' on an FWA to extend HHS's (or other Common Rule 
supporting agencies') regulatory authority to studies conducted by an 
institution that do not receive federal support would be eliminated. 
Importantly, for research other than clinical trials, institutions 
could, if they so desired, continue for purposes of their own internal 
rules to voluntarily extend the regulations to all research conducted 
by the institution, but this voluntary extension would no longer be 
part of the assurance process and the research would not be subject to 
OHRP oversight. This change would be expected to have the beneficial 
effect of encouraging some institutions to explore a variety of new 
flexible approaches to overseeing low-risk research that is not funded 
by a Common Rule agency, thus furthering the goal of this NPRM to 
decrease inappropriate administrative burdens on such research.
    In addition, the NPRM proposes to remove the provision found in the 
current Common Rule at Sec.  __.103(d) that a department or agency 
head's evaluation of an assurance will take into consideration the 
adequacy of the proposed IRB(s) designated under the assurance in light 
of the anticipated scope of the institution's activities and the types 
of subject populations likely to be involved, the appropriateness of 
the proposed initial and continuing review procedures in light of the 
probable risks, and the size and complexity of the institution.
    To further strengthen the new provision at Sec.  __.101(a) giving 
Common Rule departments and agencies explicit authority to enforce 
compliance directly against IRBs that are not affiliated with an 
assured institution, language is proposed at Sec.  __.103(e) requiring 
each IRB, institution, or organization that has oversight 
responsibility for non-exempt research involving human subjects covered 
by this policy and conducted by another institution to have and follow 
procedures for documenting the institution's reliance on the 
unaffiliated IRB and the respective responsibilities of each entity for 
meeting the regulatory requirements of this policy. This is already a 
requirement under the terms of a FWA. Such agreements would have to be 
included as part of the IRB records, per a proposed requirement at 
Sec.  __.115(a)(10). This change is proposed to address concerns about 
OHRP's current practice of enforcing compliance with the Common Rule 
through the institutions that were engaged in human subjects research, 
even in circumstances when the regulatory violation is directly related 
to the responsibilities of an external IRB.
    Finally, the NPRM would eliminate the requirement in the current 
Common Rule at Sec.  __.103(f) that grant applications undergo IRB 
review and approval for the purposes of certification. The grant 
application is often outdated by the time the research study is 
submitted for IRB review and contains detailed information about the 
costs of a study, personnel, and administrative issues that go beyond 
the mission of the IRB to protect human subjects. Therefore, experience 
suggests that review and approval of the grant application is not a 
productive use of IRB time.
    Note that each assured institution continues to have responsibility 
for ensuring that the IRBs upon which it relies are registered with 
OHRP and are appropriately constituted to review and approve the human 
subjects research, as required under Sec. Sec.  __.107 and __.108.
    In developing the NPRM proposals related to the assurance process, 
consideration was given to the 2014 SACHRP recommendation that the 
assurance of compliance required under Sec.  __.103 be provided through 
the grant-making or contract process, as one of multiple 
``Representations and Certifications'' already made by institutions 
when they apply for federal grants, contracts or cooperative 
agreements.\78\ SACHRP suggested that such a proposal may reduce 
administrative burden on IRB offices responsible for the FWA process 
without significantly diminishing the protection that these offices 
provide human subjects.
---------------------------------------------------------------------------

    \78\ See Secretary's Advisory Committee on Human Research 
Protections (SACHRP). (2014, March 13). Final Recommendations on 
Assurances and Engagement. Retrieved from SACHRP's Meetings: http://www.hhs.gov/ohrp/sachrp/mtgings/mtg03-14/assurancesandengagementrecommendations.html.
---------------------------------------------------------------------------

    Ultimately, SACHRP's recommendation was not adopted as an NPRM 
proposal because of concerns regarding the impact that removal of the 
FWA process would have on the ability for Common Rule departments and 
agencies to determine their compliance authority in certain 
circumstances. As part of SACHRP's recommended change to the assurance 
process, it was envisioned that only the primary awardee of a grant or 
contract would be required to obtain an assurance, and that this 
assurance would be provided through the grant-making or contract 
process. Subawardees or subcontractors may also be engaged in human 
subjects research, which extends the funding Common Rule department's 
or agency's authority to such institutions. However, Common Rule 
departments or agencies may not be able to ascertain that such 
institutions are required to follow the Common Rule for such human 
subjects research at their institution in the absence of an assurance 
filed with a Common Rule department or agency (including OHRP). In 
addition, some institutions have over a thousand grants or contracts 
with Common Rule departments and agencies and therefore would have over 
a thousand assurances. Certain institutional changes (for example, 
changes in the signatory official or human protections administrator) 
will require assurances to be updated. Ensuring that assurances are 
appropriately updated and keeping track of these updates are likely to 
pose challenges to Common Rule departments or agencies.
d. What would change?
     The regulatory requirement that an institution identify a 
set of ethical principles on which an institution will rely in all 
research conducted at that institution, regardless of funding source 
for the activity, would be deleted.
     The regulatory requirement that a written assurance 
include a list of IRB members for each IRB designated under the 
assurance would be replaced by the requirement that a written assurance 
include a statement that, for each designated IRB, the institution, or 
when appropriate the IRB, prepares and maintains a current detailed 
list of the IRB members with information sufficient to describe each 
member's chief anticipated contributions to IRB deliberation and any 
employment or other relationship between each member and the 
institution.
     The regulatory requirement specifying that changes in IRB 
membership be reported to the department or agency head, or to OHRP 
when the existence of an HHS-approved assurance is accepted, would be 
deleted.
     The requirement would be deleted that a department or 
agency head's evaluation of an assurance take into consideration the 
adequacy of the proposed IRB in light of the anticipated scope of the 
institution's activities and

[[Page 53992]]

the types of subject populations likely to be involved, the 
appropriateness of the proposed initial and continuing review 
procedures in light of the probable risks, and the size and complexity 
of the institution.
     For non-exempt human subjects research that takes place at 
an institution in which IRB oversight is conducted by an IRB not 
affiliated with that institution, the institution and non-affiliated 
IRB must establish and follow written procedures that identify 
compliance responsibilities of each entity that are set forth in a 
written agreement between the institution and the IRB.
e. Question for Public Comment
    88. Would protection to human subjects in research be enhanced if 
OHRP conducted routine periodic inspections to ensure that the 
membership of IRBs designated under FWAs satisfy the requirements of 
Sec.  __.107?
3. Department or Agency Discretion about Applicability of the Policy 
(NPRM at Sec.  __.101(c), (d), (i)) and Discretion Regarding Additional 
Requirements Imposed by the Conducting or Supporting Department or 
Agency (NPRM and current Rule at Sec.  __.124)
a. NPRM Goals
    The goals of the NPRM revisions in these sections are to: (1) 
Formally codify the general practice that the ethical standards 
articulated in the Belmont Report is the ethical standard that Common 
Rule departments or agencies will use in determining whether an 
activity is covered under this policy; and (2) ensure that when 
relevant, either the department or agency conducting or supporting an 
activity may require additional protections for human subjects.
b. Current Rule
    The current Common Rule allows in Sec.  __.101(c), (d), (i) for 
Federal department or agency heads to determine which specific 
activities or classes of activities are covered by the rule.
c. NPRM Proposals
    As described in section II.A.2 above, the NPRM proposes to exclude 
specific categories of low-risk research and non-research activities 
from the scope of the Common Rule in order to reduce regulatory burden. 
Of course, there will be cases that call for the exercise of careful 
judgment in determining whether activities are in an exclusion 
category, or whether they are within the scope of the Common Rule. The 
NPRM proposes to retain the Common Rule's current requirement that 
Federal department or agency heads retain final judgment about the 
coverage of particular research activities under the Common Rule (Sec.  
__.101(c)) and proposes an additional clause that Federal department or 
agency heads must exercise their authority consistent with the 
principles of the Belmont Report, in order to require these Federal 
department and agency heads to make these judgments in consideration of 
the ethical protection of human research subjects.
    The NPRM also proposes at Sec.  __.101(d) that the agency may 
require additional protections for specific types of research supported 
or conducted by the agency or department; however advance public notice 
will be required when those additional requirements apply to entities 
outside of the Federal agency itself. This requirement is intended to 
promote harmonization between Federal agencies or departments, to the 
extent possible, and to ensure transparency between funding entities 
and the regulated community.
    Finally, at Sec.  __.101(i) the NPRM proposes to amend the criteria 
for a department or agency waiving the applicability of some or all of 
the provisions of the policy, by stating that the waiver must be 
supported by an argument that the alternative procedures to be followed 
are consistent with the principles of the Belmont Report. Here again, 
the addition of this provision is to make explicit the ethical basis 
underpinning how waiver decisions have and must be considered.
    New definitions of ``Department or agency head'' and ``Federal 
department or agency'' are provided at Sec.  __.102(c) and (d) in the 
NPRM to help clarify these requirements. The NPRM proposes in Sec.  
__.102(d) adding a definition of ``Federal department or agency'' in 
order to avoid confusion as to whether this phrase encompasses Federal 
departments or agencies that do not follow the Common Rule, and to 
clarify that this phrase refers to the department or agency itself, not 
its bureaus, offices or divisions. This is consistent with HHS's 
historical interpretation of the current Rule. To distinguish this from 
the definition of Department or agency head found in the current 
regulations at Sec.  __.102(a) (and found in the NPRM at Sec.  
__.102(c)), the example of the Secretary of HHS has been inserted to 
provide clarity. In addition, the definition of ``institution'' has 
been changed at Sec.  __.102(f) in the NPRM to clarify that departments 
can be considered institutions for the purposes of this policy.
4. Research Covered by This Policy Conducted in Foreign Countries (NPRM 
at Sec.  __.101(h))
    The current Common Rule at Sec.  __.101(h) articulates that when 
research covered by this policy takes place in foreign countries, 
procedures normally followed in the foreign countries to protect human 
subjects may differ from those set forth in this policy. The current 
provision provides the Declaration of Helsinki, as amended in 1989, as 
an example of internationally recognized ethical standards that a 
foreign country might use as its ethical base. In this situation, the 
current Common Rule provides that if a department or agency head 
determines that the procedures prescribed by the institution afford 
protections that are at least equivalent to those provided in this 
policy, the department or agency head may approve the substitution of 
the foreign procedures in lieu of the procedural requirements provided 
in this policy.
    The NPRM proposes to remove the specific example provided in this 
provision. A concern with providing a specific example of 
internationally recognized ethical document is that such a document is 
subject to change independent of HHS or other Common Rule agencies, and 
therefore could be modified to contain provisions that are inconsistent 
with U.S. laws and regulations.

I. Effective and Compliance Dates of New Rule (NPRM at Sec.  __.101(k))

1. Effective Dates
    It is anticipated that the effective date of the final rule will be 
one year after publication in the Federal Register. The compliance date 
of the new rules would also be one year from the publication of the 
Final Rule, with two exceptions discussed below. However, a provision 
that is anticipated to provide additional regulatory flexibility to 
institutions or investigators could voluntarily be implemented 90 days 
from the publication of the Final Rule. This 90-day delay would give 
the Common Rule departments and agencies time to develop the documents 
and tools needed to assist institutions in implementing some of these 
provisions (e.g., the Secretary's broad consent template, and privacy 
safeguards under Sec.  __.105). The provisions that would provide 
additional regulatory flexibility include:
     the proposed exclusions in Sec.  __.101(b);

[[Page 53993]]

     the proposed exemptions in Sec.  __.104(d), (e) and (f);
     the proposal to no longer require IRB review of grant 
applications (Sec.  __.103(f) in the current Common Rule);
     the proposal to eliminate the regulatory requirement in 
Sec.  __.103 specifying that changes in IRB membership be reported to 
the department or agency head, or to OHRP when an HHS-approved 
assurance is approved;
     the proposed provision in Sec.  __.109(f) to eliminate the 
continuing review requirement for studies that undergo expedited review 
and for studies that have completed study interventions and are merely 
analyzing data or involve only observational follow up in conjunction 
with standard clinical care;
     the proposed provision in Sec.  __.116(g) stating that an 
IRB may approve a research proposal in which investigators obtain 
identifiable private information without individuals' informed consent 
for the purpose of screening, recruiting, or determining the 
eligibility of prospective human subjects of research, through oral or 
written communication or by accessing records, in order to obtain 
informed consent, if the research proposal includes an assurance that 
the investigator will implement standards for protecting the 
information obtained in accordance with and to the extent required by 
the Sec.  __.105 privacy safeguards; and
     the new provision in Sec.  __.117(c)(1)(iii) allowing a 
waiver of the requirement for a signed consent form if the subjects are 
members of a distinct cultural group or community for whom signing 
documents is not the norm, the research presents no more than minimal 
risk of harm to subjects, and there is an appropriate alternative 
method for documenting that informed consent was obtained.
    In two cases, institutions would have longer than one year to 
comply: (1) The proposal for the Common Rule to cover all biospecimens 
(Sec.  __.102(e) in the NPRM); and (2) the proposal in Sec.  
__.114(b)(1) regarding identifying a single IRB that would be 
responsible for the review of certain multi-institutional clinical 
trials. The compliance date for these requirements would be three years 
after the publication of the final rule to allow institutions the 
necessary time to develop institutional policies and procedures 
necessary to implement these provisions. Comment is sought about 
whether a different approach to phasing in these provisions would allow 
the regulated community to better implement the changes proposed in 
this NPRM. Additional possibilities discussed amongst the Common Rule 
agencies included providing smaller institutions more time to implement 
these two changes, and somehow incentivizing early compliance with 
these provisions.
    Further, the extension of the regulations to clinical trials that 
are not directly funded by a Common Rule department or agency, but that 
are conducted at an institution that receives funding from a Common 
Rule department or agency for other human subjects research, would not 
apply to an institution until the institution received federal funding 
for non-exempt research in an award made after the effective date of 
the final rule.
2. Transition Provisions
    The ANPRM suggested that any change related to the extent to which 
biospecimens are covered under the Common Rule would only apply to 
biospecimens collected after the effective date of the revised Common 
Rule. Commenters noted concerns about imposing consent requirements on 
the use of biospecimens already collected--that is, not grandfathering 
in such resources--especially if these biospecimens are non-identified. 
Requiring that consent be obtained for the use of these materials could 
result in their being rendered useless for research, which would 
represent a cost of its own in terms of lost opportunity. This concern 
was based on the practical limitations involved in obtaining consent 
for biospecimens that were de-identified in the past, given that it may 
not be possible to re-contact the original source.
a. Research Initiated Prior to the Effective Date of This Subpart (NPRM 
at Sec.  __.101(k)(1))
    The NPRM addresses the transition provisions for human subjects 
research (as defined in the NPRM) initiated before the effective date 
of the policy. Ongoing human subjects research initiated prior to the 
effective date of the final rule may choose to comply with the 
provisions that provide additional regulatory flexibility discussed 
above, but would not need to comply with additional requirements 
related to:
     Coverage of clinical trials (Sec.  __.101(a)(2));
     Written procedures for documenting an institution's 
reliance on an unaffiliated IRB (Sec.  __.103(e));
     New exempt research categories and determination 
requirements (Sec.  __.104(c)-(f));
     Information and biospecimen protection requirements (Sec.  
__.105);
     New IRB roster and written procedural requirements (Sec.  
__.108(a)(2));
     Continuing review requirements (Sec.  __.109(f)(2));
     Additional IRB approval criteria for information 
safeguards and return of results plans (Sec.  __.111(a)(7) and (8));
     Requirements for cooperative research (Sec.  __.114);
     IRB recordkeeping requirements for documenting an 
institution's reliance on an unaffiliated IRB and exemption 
determinations (Sec.  __.115(a)(10) and (11)); and
     Requirements for obtaining and documenting informed 
consent (Sec. Sec.  __.116 and __.117) that become effective on the 
date of the final rule.
b. Use of Prior Collections of Biospecimens (NPRM at Sec.  
__.101(k)(2))
    Research involving the use of prior collections of biospecimens is 
permitted if the biospecimens were collected for either research or 
non-research purposes before the effective date of this subpart, and 
research use of the biospecimens occurs only after removal of any 
individually identifiable information associated with the biospecimens.
    If prior collections of biospecimens are not individually 
identifiable, research using such non-identified biospecimens would 
continue to be not covered by the regulations even after the effective 
date of this policy.
    Similarly, if prior collections of biospecimens are being stored or 
maintained in an individually identifiable form, but identifiers are 
removed from the biospecimens before being obtained by an investigator, 
the investigator's use of such nonidentifiable biospecimens would 
continue to be not covered by the regulations even after the effective 
date of this policy.

III. Regulatory Impact Analyses

A. Introduction

    HHS has examined the impacts of this proposed rule under Executive 
Order 12866 on Regulatory Planning and Review (September 30, 1993); 
Executive Order 13563 on Improving Regulation and Regulatory Review 
(January 18, 2011); the Regulatory Flexibility Act of 1980, Public Law 
96-354 (September 19, 1980); the Unfunded Mandates Reform Act of 1995, 
Public Law 104-4, (March 22, 1995); and Executive Order 13132 on 
Federalism (August 4, 1999).
    Executive Order 12866 directs agencies to assess all costs and 
benefits of available regulatory alternatives and, if regulation is 
necessary, to select

[[Page 53994]]

regulatory approaches that maximize net benefits (including potential 
economic, environmental, public health and safety effects; distributive 
impacts; and equity). Executive Order 13563 is supplemental to and 
reaffirms the principles, structures, and definitions governing 
regulatory review as established in Executive Order 12866. HHS expects 
that this proposed rule would have an annual effect on the economy of 
$100 million or more in any one year and therefore is a significant 
regulatory action as defined by Executive Order 12866.
    The Regulatory Flexibility Act (RFA) requires agencies that issue a 
regulation to analyze options for regulatory relief of small businesses 
if a rule has a significant impact on a substantial number of small 
entities.\79\ The RFA generally defines a ``small entity'' as (1) a 
proprietary firm meeting the size standards of the Small Business 
Administration (SBA); (2) a nonprofit organization that is not dominant 
in its field; or (3) a small government jurisdiction with a population 
of less than 50,000 (states and individuals are not included in the 
definition of ``small entity'').\80\ HHS considers a rule to have a 
significant economic impact on a substantial number of small entities 
if at least 5 percent of small entities experience an impact of more 
than 3 percent of revenue. HHS anticipates that the proposed rule would 
not have a significant economic impact on a substantial number of small 
entities. Supporting analysis is provided in section III.G below.
---------------------------------------------------------------------------

    \79\ 5 U.S.C. 603
    \80\ 5 U.S.C. 601
---------------------------------------------------------------------------

    Section 202(a) of the Unfunded Mandates Reform Act of 1995 \81\ 
requires that agencies prepare a written statement, which includes an 
assessment of anticipated costs and benefits, before proposing ``any 
rule that includes any Federal mandate that may result in the 
expenditure by State, local, and tribal governments, in the aggregate, 
or by the private sector, of $100,000,000 or more (adjusted annually 
for inflation) in any one year.'' The current threshold after 
adjustment for inflation is $141 million, using the most current (2013) 
implicit price deflator for the gross domestic product. HHS expects 
this proposed rule to result in expenditures that would exceed this 
amount.
---------------------------------------------------------------------------

    \81\ 2 U.S.C. 1532
---------------------------------------------------------------------------

    Executive Order 13132 establishes certain requirements that an 
agency must meet when it promulgates a rule that imposes substantial 
direct requirement costs on state and local governments or has 
federalism implications. HHS has determined that the proposed rule, if 
finalized, would not contain policies that would have substantial 
direct effects on the States, on the relationship between the National 
Government and the States, or on the distribution of power and 
responsibilities among the various levels of government. The proposed 
changes in the rule represent the Federal Government regulating its own 
program. Accordingly, HHS concludes that the proposed rule does not 
contain policies that have federalism implications as defined in 
Executive Order 13132 and, consequently, a federalism summary impact 
statement is not required.

B. Summary of the Proposed Rule

    This NPRM is being issued to propose revisions to modernize, 
strengthen, and make more effective the current regulations for 
protecting human subjects. This proposed rule enhances clarity and 
transparency of the consent process by imposing stricter new 
requirements regarding the information that must be given to 
prospective subjects including the elements of consent in a variety of 
circumstances. It will also allow consent to the secondary research use 
of biospecimens and identifiable private information, given specific 
conditions are met. Enhanced protections to subjects are also achieved 
through greater transparency by posting of informed consent forms used 
in clinical trials. Several proposed changes (such as explicitly 
excluding certain activities from the rule, expanding the categories of 
research exempt from some of the requirements of the proposed rule, and 
eliminating continuing review by an IRB in some situations) would 
relieve the burden of unnecessary or unwarranted stringent review of 
some low-risk studies that do not pose threats to the welfare of 
subjects. Other proposed changes expand the reach of the regulations by 
covering all clinical trials, regardless of funding source, and by 
changing the definition of human subject to include research in which 
an investigator uses, studies, or analyzes a biospecimen. Single IRB 
review for multi-institutional studies would also be generally 
required, except where local IRB review is required by law, to reduce 
duplicative IRB reviews. Still other revisions clarify or revise 
requirements for and responsibilities of IRB review and documentation. 
New exempt categories are proposed, requiring that investigators and 
institutions comply with minimum standards for protecting privacy. A 
new process is also proposed through which investigators may input 
information about a prospective study into a tool in order for that 
tool to generate exemption determinations.
1. Accounting Table
    Table 1 summarizes the quantified and non-quantified benefits and 
costs of all proposed changes to the Common Rule. Over the 2016-2025 
period, present value benefits of $2,629 million and annualized 
benefits of $308 million are estimated using a 3 percent discount rate; 
present value benefits of $2,047 million and annualized benefits of 
$291 million are estimated using a 7 percent discount rate. Present 
value costs of $13,342 million and annualized costs of $1,564 million 
are estimated using a 3 percent discount rate; present value costs of 
$9,605 million and annualized costs of $1,367 million are estimated 
using a 7 percent discount rate. Non-quantified benefits include 
improved human subjects protections in clinical trials and biospecimen 
research not currently subject to oversight; enhanced oversight of 
research reviewed by unaffiliated IRBs; increased uniformity in 
regulatory requirements among Common Rule agencies; standardization of 
human subjects protections when variation among review IRBs is not 
warranted; revised informed consent forms and processes; improved 
protection of biospecimens and identifiable private information; and 
increased transparency of Common Rule agency-supported clinical trials 
to inform the development of new consent forms. Non-quantified costs 
include the time needed for consultation among Common Rule agencies 
before federal guidance is issued; and the time needed by investigators 
to obtain, document, and track the permissible uses of biospecimens and 
identifiable private information for secondary research use.

[[Page 53995]]



                     Table 1--Accounting Table of Benefits and Costs of All Proposed Changes
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits.....................            2,629             2,047               308               291
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Improved human subjects protections in clinical trials and biospecimen research not currently subject to
     oversight; enhanced oversight in research reviewed by unaffiliated IRBs; increased uniformity in regulatory
     requirements among Common Rule agencies; ethical benefit of respecting an individual's wishes in how his or
     her biospecimens are used in future research; standardization of human subjects protections when variation
     among review IRBs is not warranted; improved informed consent forms and processes; improved protection of
     biospecimens and identifiable private information; better ensuring availability of biospecimens for future
     research activities; and increased transparency of Common Rule-supported clinical trials to inform the
     development of new consent forms...........................................................................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs                                   13,342             9,605             1,564             1,367
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    Time for consultation among Common Rule agencies before federal guidance is issued; time for investigators
     to obtain consent for secondary use of biospecimens or identifiable private information....................
----------------------------------------------------------------------------------------------------------------

    Table 2 summarizes the quantified present value benefits and costs 
of each proposed change to the Common Rule using a 3 percent discount 
rate.

   Table 2--Accounting Table of Quantified Benefits and Costs of Each
                             Proposed Change
------------------------------------------------------------------------
                                      Present value of 10 years at a  3
                                     percent discount rate  (millions of
          Proposed change                       2013 dollars)
                                   -------------------------------------
                                         Benefits            Costs
------------------------------------------------------------------------
Costs to Learn New Requirements     .................                208
 and Develop Training Materials;
 OHRP Costs to Develop Training
 and Guidance Materials, and To
 Implement the Rule...............
Extending Oversight to IRBs         .................               84.6
 Unaffiliated With an Institution
 Holding an FWA...................
Extending Common Rule Compliance    .................               18.3
 Oversight to Clinical Trials
 Regardless of Funding Source.....
Excluding Activities from the                    74.0  .................
 Requirements of the Common Rule
 because They are not Research....
Excluding Low-Risk Research from                  740  .................
 the Requirements of the Common
 Rule.............................
Clarifying and Harmonizing          .................  .................
 Regulatory Requirements and
 Agency Guidance..................
Expanding the Definition of Human   .................                101
 Subject to Include Research
 involving Non-Identified
 Biospecimens and Creating an
 Exemption for Secondary Research
 Using Biospecimens or
 Identifiable Private Information.
Modifying the Assurance                          5.81  .................
 Requirements.....................
Requirement for Written Procedures  .................               11.3
 and Agreements for Reliance on
 External IRBs....................
Eliminating the Requirement that                  310  .................
 the Grant Application Undergo IRB
 Review and Approval..............
Tracking and Documenting Exemption  .................  .................
 Determinations...................
Amending the Research and                        37.0               0.36
 Demonstration Project Exemption..
Expansion of Research Activities                 70.0  .................
 Exempt from IRB Review...........
Exemption for the Storage and       .................               1.58
 Maintenance of Biospecimens and
 Identifiable Private Information
 for Future, Unspecified Secondary
 Research Activities after Consent
 has been Sought and Obtained.....
Protection of Information and       .................                457
 Biospecimens.....................
Elimination of Continuing Review                  145               38.8
 of Research Under Specific
 Conditions.......................
Amending the Expedited Review                    16.8               2.71
 Procedures.......................
Revised Criteria for IRB Approval                 126               0.07
 of Research......................
Cooperative Research..............              1,103                155
Changes in the Basic Elements of    .................               4.55
 Consent, Including Documentation.
Obtaining Consent to Secondary Use  .................             12,245
 of Biospecimens and Identifiable
 Private Information..............
Elimination of Requirement to                    1.21  .................
 Waive Consent in Certain Subject
 Recruitment Activities...........
Requirement for Posting of Consent  .................               14.6
 Forms for Clinical Trials
 supported by Common Rule
 Department or Agencies...........
Alteration in Waiver for            .................  .................
 Documentation of Informed Consent
 in Certain Circumstances.........
------------------------------------------------------------------------

C. Need for the Proposed Rule

    Federal regulations governing the protection of human subjects in 
research have been in place for more than three decades, and 20 years 
have passed since the Common Rule was adopted by 15 Federal departments 
and agencies \82\ in

[[Page 53996]]

an effort to promote uniformity, understanding, and compliance with 
human subject protections. Today 18 departments and agencies have 
adopted the rule.\83\ As such, compliance with the Common Rule is a 
condition for receiving federal funding from one of these agencies. 
Note that an additional agency (Department of Labor) is joining this 
proposed rulemaking in order to promulgate the Common Rule in DOL 
regulations and to apply the regulations to human subjects research 
that DOL may conduct or support, pending the scope of the final rule. 
Although professional organizations have codes of conduct and 
guidelines for members conducting research, only the Federal government 
has the authority to regulate the activities of institutions using 
public funds for human subjects research. Since the Common Rule was 
developed, the volume of research has increased, evolved, and 
diversified. Although the regulations have been amended over the years, 
the enterprise has changed to the point that the current regulations 
might be outdated in some important ways.
---------------------------------------------------------------------------

    \82\ The current 15 Common Rule signatory agencies are: 
Department of Agriculture; Department of Energy; National 
Aeronautics and Space Administration; Department of Commerce; 
Consumer Product Safety Commission; Agency for International 
Development; Department of Housing and Urban Development; Department 
of Justice; Department of Defense; Department of Education; 
Department of Veterans Affairs; Environmental Protection Agency; 
Department of Health and Human Services; National Science 
Foundation; and Department of Transportation.
    \83\ In addition to the signatory Common Rule departments and 
agencies, three departments and agencies have not issued the Common 
Rule but currently apply 45 CFR Part 46: The Central Intelligence 
Agency, the Social Security Administration, and the Department of 
Homeland Security.
---------------------------------------------------------------------------

    Under the current system, the regulated community notes that 
limited IRB resources are often diverted away from focusing on higher-
risk studies because of the considerable time spent reviewing low-risk 
and minimal-risk research. Theoretically, this can result in inadequate 
attention devoted to research that could seriously harm subjects and 
unnecessary delay of very low-risk research. From the perspective of 
human subjects participating in research, the length and complexity of 
consent forms has been increasing even for relatively low-risk studies, 
hindering subject understanding of the research activities in which 
they participate. Current and prospective research subjects have 
increasingly indicated that they would like to be asked about the 
future research use of their biospecimens. This desire is not 
necessarily based on concern of inappropriate disclosure or use of 
personally identifiable private information generated from the 
biospecimen, but rather is rooted in the sense that subjects should, 
whenever possible, be asked about such future research use. Finally, 
the current system contains some oversight gaps that should be 
addressed to ensure that the system is covering the riskiest studies 
and that should compliance-related issues occur, the IRBs responsible 
for these issues may be held responsible. Provisions are needed to 
ensure the Rule's consistency with the principles of Belmont Report and 
to protect privacy in the context of increasing cybercrime and the 
introduction of modern research methods that may jeopardize subject 
privacy while not unnecessarily slowing research.
    Thus, this NPRM proposes a number of measures to address the issues 
described above. Provisions that strengthen the requirements for 
informed consent and promote transparency in the informed consent 
process include: (1) Requiring that the informed consent form be 
designed and presented in such a way that facilitates a prospective 
subject's understanding of why one would want to participate in a 
research study or not; (2) requiring that the informed consent form 
present the required information before providing any other information 
to a prospective subject; (3) revising and adding to the required 
elements of consent; (4) requiring for certain clinical trials the 
posting of a copy of at least one version of a consent form on a 
publicly available federal Web site; and (5) changing the conditions 
and requirements for waiver or alteration of consent to remove 
ambiguity, including a new provision that under specific conditions an 
IRB may approve a research proposal in which investigators obtain 
identifiable private information without individuals' informed consent 
for the purpose of screening, recruiting, or determining eligibility of 
prospective human subjects of research.
    Provisions that strengthen humans subjects protections include: (1) 
A provision that would hold IRBs not affiliated with engaged 
institutions directly responsible for compliance; (2) extending the 
scope of the policy to research most likely to involve greater-than-
minimal risk, that is, clinical trials; and (3) creating standard 
privacy safeguards for biospecimens and information.
    Provisions that strengthen the extent to which the ethics system 
promotes the principle of respect for persons: (1) Requiring informed 
consent for most research activities involving biospecimens, regardless 
of identifiability; (2) allowing for waiver of informed consent in 
research activities involving biospecimens only in rare circumstances; 
and (3) adding a provision that would prohibit waiver of consent if 
someone has been asked to provide their broad consent for future 
research use of their biospecimens or identified private information, 
and that person refuses to give such consent.
    New provisions that would allow IRBs greater flexibility to focus 
resources on higher-risk research include: (1) Distinguishing 
categories of activities that would be excluded from the rule; and (2) 
expanding and clarifying categories of exempt research. Provisions that 
streamline or reduce burden for IRBs or institutions include: (1) 
Requiring consultation among the Common Rule agencies for the purpose 
of harmonizing guidance; (2) eliminating an administrative requirement 
for reporting IRB rosters; (3) removing the requirement that IRBs must 
review and approve grant applications; (4) eliminating under certain 
specific circumstances, continuing review for minimal risk studies that 
undergo expedited review; (5) clarifying when expedited review can 
occur; and (6) mandating use of a single IRB for multi-institutional 
studies.

D. Analysis of Benefits and Costs

    In this section, the analysis of the quantified and non-quantified 
benefits and costs of the proposed changes to the Common Rule are 
presented. First, the common assumptions of the analysis are discussed. 
Then, this section presents the estimated quantified and non-quantified 
benefits and costs of the specific changes. Because of the lack of 
available data about IRB effectiveness and how IRBs function 
operationally,\84\ many of the estimations in this analysis are based 
on anecdotal evidence. On all assumptions and estimates presented 
below, public comment is requested on the accuracy of these assumptions 
and on whether better data sources are available to support the 
analysis.
---------------------------------------------------------------------------

    \84\ See, e.g.,, L Abbott and C. Grady, A Systematic Review of 
the Empirical Literature Evaluating IRBs: What We Know and What We 
Still Need to Learn. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235475/.
---------------------------------------------------------------------------

1. Analytic Assumptions
    The analysis relies on common data elements and assumptions, 
detailed below, concerning the domestic entities, individuals, and IRB 
reviews affected by the proposed changes to the Common Rule. Many of 
the estimates are derived from a 1998 NIH-sponsored evaluation of the 
implementation of Section 491 of the Public Health Service Act, which 
involved nationally representative surveys of IRBs, institutions, and 
investigators. Based on a review of the literature, this study contains 
the best available data on the time spent on protocol reviews as well 
as the

[[Page 53997]]

characteristics of the reviews themselves. As previously stated, public 
comment is requested on these and other estimates used throughout the 
analysis.
    According to the OHRP database of registered institutions and IRBs, 
there are approximately 8,035 institutions with a FWA, of which 2,871 
have an IRB. Some institutions have multiple IRBs and some IRBs are not 
affiliated with an institution with an FWA, for a total of 3,499 IRBs.
    The OHRP database of registered institutions and IRBs shows that 
there are 675,390 annual reviews of non-exempt protocols involving 
human subjects. It is estimated that there are 324,187 initial protocol 
reviews (48 percent) and 351,203 continuing protocol reviews (52 
percent) based on estimates reported in Bell et al.\85\ In each 
category, it is estimated that 69 percent of these reviews are convened 
and 31 percent are expedited based on estimates reported in Bell et al. 
It is estimated that there are 472,773 reviews of single-site protocols 
(70 percent) and 202,617 reviews of multi-site protocols (30 percent) 
based on estimates reported in Bell et al. This analysis also assumes 
that there are on average 5 IRB reviews per multiple-site protocol. 
This implies that there are 472,773 single-site protocols and 40,523 
multi-site protocols, for a total of 513,296 protocols. The above 
implies that there are approximately 246,382 new protocols each year.
---------------------------------------------------------------------------

    \85\ Bell J, Whiton J, and Connelly S, Final Report: Evaluation 
of NIH Implementation of Section 491 of the Public Health Service 
Act, Mandating a Program of Protection for Research Subjects, 1998.
---------------------------------------------------------------------------

    Based on queries of ClinicalTrials.gov, it is estimated that HHS 
supports 909 new clinical trials annually, of which 575 are regulated 
by FDA. In addition, it is estimated that there are 1,399 clinical 
trials currently not subject to oversight by either the Common Rule or 
FDA regulations. Finally, based on queries of ClinicalTrials.gov, 
Common Rule agencies support approximately 5,270 studies total.
    Many individuals in various occupations would be affected by the 
proposed changes to the Common Rule. It is estimated that an average of 
one institution official at each institution with an FWA would be 
affected by these changes, for a total of 2,871 institution officials. 
The OHRP database of registered institutions and IRBs shows that there 
are 10,197 full-time equivalents (FTEs) staff persons at IRBs working 
as administrators or administrative staff, and that 89.8 percent of 
IRBs have an administrator. It is assumed that these individuals work 
full-time, implying a total of 3,193 IRB administrators and 7,004 IRB 
administrative staff. The OHRP database of IRB rosters contains 3,359 
individuals who serve as IRB chairs and an additional 32,518 voting 
members. The number of IRB chairs is less than the number of IRBs 
because some individuals chair multiple IRBs. It is assumed that there 
are 439,968 investigators who conduct human subjects research in the 
United States.\86\
---------------------------------------------------------------------------

    \86\ To derive this estimate, the number of new protocols, 
estimated above, is divided by the average number of new protocols 
submissions reported per investigator. This is estimated to be 2.8 
based on Bell et al. This number is then multiplied by the average 
number of investigators working on each protocol (which is assumed 
to be 5). This allows for an accounting of investigators working on 
multiple protocols as well as protocols with multiple investigators.
---------------------------------------------------------------------------

    The hourly wages of individuals affected by the proposed changes to 
the Common Rule is estimated using information on annual salaries 
provided by the U.S. Bureau of Labor Statistics and the U.S. Office of 
Personal Management. The salary of postsecondary education 
administrators is used as a proxy for the salary of institution 
officials; the salary of lawyers is used as a proxy for the salary of 
institution legal staff and IRB administrators; the salary of office 
and administrative support workers is used as a proxy for the salary of 
IRB administrative staff; the salary of postsecondary health teachers 
is used as a proxy for the salary of IRB chairs and IRB voting members; 
the salary of postsecondary teachers is used as a proxy for the salary 
of investigators; the salary of database and systems administrators and 
network architects is used as a proxy for the salary of database 
administrators; and the salary of all occupations, as a proxy for the 
salary of prospective human subjects. The federal employees affected by 
the proposed changes to the Common Rule are assumed to be Step 5 within 
their GS-level and earn locality pay for the District of Columbia, 
Baltimore, and Northern Virginia. Annual salaries are divided by 2,087 
hours to derive hourly wages. To project wages over 2016-2025, wages 
are adjusted for growth over time using the average annual per capita 
growth in real wage income over 1929-2012 reported by the U.S. Bureau 
of Economic Analysis, which is 2.1 percent. The total dollar value of 
labor, which includes wages, benefits, and overhead, is assumed to be 
equal to 200 percent of the wage rate.
    The RIA calculates person-hours by occupation per initial protocol 
review and per continuing protocol review based on each occupation's 
share of total person-hours reported in Bell et al. In particular, Bell 
et al. reports that institution officials account for 4 percent, IRB 
administrators account for 28 percent, IRB administrative staff account 
for 30 percent, IRB chairs account for 7 percent, and IRB voting 
members account for 31 percent of total person-hours. The RIA assumes 
that the average number of person-hours spent per review equals the 
weighted average of the person-hours spent per convened review and the 
person-hours spent per expedited review. It is further assumed that 
convened review requires twice as many person-hours as expedited 
review.
    Table 3 shows the number of entities affected by the proposed 
changes to the Common Rule and other common assumptions of the analysis 
(described above).

    Table 3--Number of Affected Entities and Other Common Assumptions
------------------------------------------------------------------------
                       Description                           Estimate
------------------------------------------------------------------------
                       U.S. Institutions and IRBs
------------------------------------------------------------------------
Institutions with a Federalwide Assurance...............           8,035
Institutions with an IRB................................           2,871
Institutions without an IRB.............................           5,164
IRBs....................................................           3,499
------------------------------------------------------------------------
                               Occupations
------------------------------------------------------------------------
Institution officials...................................           2,871

[[Page 53998]]

 
IRB administrators......................................           3,193
IRB administrative staff................................           7,004
IRB chairs..............................................           3,359
IRB voting members......................................          32,518
Investigators...........................................         439,968
------------------------------------------------------------------------
                              Hourly Wages
------------------------------------------------------------------------
Institution officials (2013)............................          $48.20
Institution legal staff (2013)..........................          $63.24
IRB administrators (2013)...............................          $63.24
IRB administrative staff (2013).........................          $16.72
IRB chairs (2013).......................................          $46.36
IRB voting members (2013)...............................          $46.36
Investigators (2013)....................................          $35.75
Database administrators (2013)..........................          $38.69
Prospective Human Subjects (2013).......................          $22.25
Federal employees in the District of Columbia,
 Baltimore, and Northern Virginia (2013):
     GS-9 Step 5........................................          $28.04
     GS-13 Step 5.......................................          $48.35
     GS-14 Step 5.......................................          $57.13
     GS-15 Step 5.......................................          $67.21
Average annual per capita growth in real wage income....            2.1%
------------------------------------------------------------------------
  IRB Reviews of Human Subjects Research Protocols at U.S. Institutions
------------------------------------------------------------------------
Annual reviews of non-exempt protocols..................         675,390
    Initial protocol reviews (48%)......................         324,187
         Convened reviews (69%).........................         223,689
         Expedited reviews (31%)........................         100,498
    Continuing protocol reviews (52%)...................         351,203
         Convened reviews (69%).........................         242,330
         Expedited reviews (31%)........................         108,873
Annual reviews of single-site protocols (70%)...........         472,773
Annual reviews of multi-site protocols (30%)............         202,617
------------------------------------------------------------------------
         Human Subjects Research Protocols at U.S. Institutions
------------------------------------------------------------------------
Active protocols........................................         513,296
    Single-site protocols...............................         472,773
    Multi-site protocols................................          40,523
New protocols (48%).....................................         246,382
Average number of IRB reviews per active multi-site                    5
 protocol...............................................
------------------------------------------------------------------------
                             Clinical Trials
------------------------------------------------------------------------
New clinical trials supported by HHS annually...........             909
    Regulated by FDA....................................             575
Active clinical trials currently not regulated by the              1,399
 Common Rule or FDA regulations.........................
Clinical Trials supported by Common Rule Agencies.......           5,270
------------------------------------------------------------------------
   Person-Hours per Protocol Reviewed by Occupation and Type of Review
------------------------------------------------------------------------
Institution officials:
    Initial protocol reviews
        Convened reviews................................            0.52
        Expedited reviews...............................            0.26
    Continuing protocol reviews:
        Convened reviews................................            0.10
        Expedited reviews...............................            0.05
IRB administrators:
    Initial protocol reviews:
        Convened reviews................................            3.64
        Expedited reviews...............................            1.82
    Continuing protocol reviews:
        Convened reviews................................            0.68
        Expedited reviews...............................            0.34
IRB administrative staff:
    Initial protocol reviews:...........................
        Convened reviews................................            3.91
        Expedited reviews...............................            1.95
    Continuing protocol reviews:
        Convened reviews................................            0.73

[[Page 53999]]

 
        Expedited reviews...............................            0.36
IRB chairs:
    Initial protocol reviews:
        Convened reviews................................            0.91
        Expedited reviews...............................            0.46
    Continuing protocol reviews:
        Convened reviews................................            0.17
        Expedited reviews...............................            0.08
IRB voting members:
    Initial protocol reviews:
        Convened reviews................................            2.70
        Expedited reviews...............................            1.35
        Exempt reviews..................................            0.50
    Continuing protocol reviews:
        Convened reviews................................            0.75
        Expedited reviews...............................            0.38
Investigators:
    Initial protocol reviews:
        Convened reviews................................           13.65
        Expedited reviews...............................            7.15
        Exempt reviews..................................            0.50
    Continuing protocol reviews:
        Convened reviews................................            6.83
        Expedited reviews...............................            3.58
------------------------------------------------------------------------

2. Analysis of Proposed Changes
    Presented below is an analysis of the quantified and non-quantified 
benefits and costs of the proposed changes to the Common Rule. For each 
proposed change, we describe and explain the need for the change, 
provide a qualitative summary of the anticipated benefits and costs, 
describe the methods we use to quantify benefits and costs, and then 
present estimates.
a. Costs for the Regulated Community to Learn New Requirements and 
Develop Training Materials; Costs for OHRP to Develop Materials and 
Guidance
    Domestic institutions, IRBs, and investigators would need to spend 
time learning the proposed changes to the Common Rule once training 
materials become available to them. In addition, IRBs and OHRP would 
need to update training materials for investigators. Finally, OHRP 
would need to develop guidance, templates, lists, and a number of 
electronic resources (as stated in the NPRM).
    The RIA estimates that institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators would each spend 5 hours to learn the proposed changes to 
the Common Rule. It is also estimated that institution officials would 
spend two hours to learn new procedures, IRB administrators would spend 
20 hours, and administrative staff would spend 80 hours. Based on the 
estimates presented in Table 3, the dollar value of their time is 
calculated by multiplying hours by their estimated 2016 wages and 
adjusting for overhead and benefits. For example, to calculate the 
dollar value of time spent by institution officials to learn the 
proposed changes to the Common Rule in 2016, we multiply the number of 
institution officials (2,871) by the number of hours spent per 
institutional official (5), by the projected hourly wage of institution 
officials ($48.20), and by the adjustment factor for benefits and 
overhead (2).
    In order to develop the resources required by the NPRM, it is 
anticipated that OHRP would need:
     Three staff people at the GS-14 level to: (1) Promote 
harmonization efforts to issue guidance across Common Rule agencies and 
departments; (2) develop a number of ``Secretary's Lists'' (akin to 
guidance documents) referenced in the rule that would be periodically 
reviewed and revised; (3) develop template agreements/contracts for use 
by the regulated community; (4) manage the administrative transition to 
the new processes proposed in the NPRM; and, (5) develop the language 
and technical requirements for a web-based tool that would allow 
investigators (and others) to determine if a project fits into a 
category of research exempt from certain regulatory requirements.
     One staff person at the GS-13 level to manage process 
changes proposed in the NPRM, and assist with implementation for the 
web-based tools and portals proposed.
     One staff person at the GS-9 level to provide technical 
support for the web-based portals proposed in the NPRM.
    In addition, the first year after a final rule is published 
staffing resources beyond what is described above would be necessary:
     Three staff people at the GS-14 level to draft new 
guidance and revise old guidance.
     One staff person at the GS-14 level to conduct educational 
seminars.
    OHRP also anticipates the following in non-personnel costs:
     Technical development of a web-based tool that 
investigators (and others) may use to determine if a project fits into 
a category of research that is exempt from certain regulatory 
requirements ($350,000)
     Technical development of two web-based portals for 
investigators to post final consent forms for HHS-funded clinical 
trials, and for investigators that conduct certain types of 
demonstration projects to post information about said projects 
($200,000)
     Developing five educational seminars (including travel) to 
educate the public about the requirements of the new rule ($200,000)
     Upgrading equipment for education activities ($50,000)
    Present value costs of $208 million and annualized costs of $24.3 
million are estimated using a 3 percent discount rate; present value 
costs of $199 million and annualized costs of $28.3 million are 
estimated using a 7 percent discount rate. Table 4 summarizes the 
quantified

[[Page 54000]]

and non-quantified benefits and costs to learn new requirements and 
develop training materials.

    Table 4--Summary of Estimated Benefits and Costs To Learn New Requirements and Develop Training Materials
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    None (although benefits discussed in
     association with other provisions
     would be impossible without this
     activity)..........................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Time and money to learn new                       208               199              24.3              28.3
     requirements, update training
     materials, and develop tools.......
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

b. Extending Oversight to IRBs Unaffiliated With an Institution Holding 
a Federalwide Assurance (NPRM at Sec.  __.101(a))
    The NPRM proposes a change to place unaffiliated IRBs within the 
realm of entities to which the policy applies. This new provision gives 
Common Rule departments and agencies explicit authority to enforce 
compliance directly against IRBs that are not affiliated with an 
assured institution. This change addresses concerns about OHRP's 
current practice of enforcing compliance with the Common Rule through 
the institutions that were engaged in human subjects research, even in 
circumstances when the regulatory violation is directly related to the 
responsibilities of an external IRB. This change should encourage 
institutions to more willingly rely on qualified unaffiliated IRBs for 
cooperative research, as is required under the proposed changes at 
Sec.  __.114 (see section III.D.2.s of this RIA below).
    The OHRP database of assured institutions and registered IRBs shows 
that there are approximately 449 IRBs not affiliated with an 
institution holding an FWA that would now be subject to oversight. 
These IRBs would develop an estimated average of 10 written agreements 
with other institutions each year as a result of this proposal. It is 
further estimated that each agreement would require an average of 10 
hours of institution legal staff time and 5 hours of IRB administrator 
time to complete.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    Present value costs of $84.6 million and annualized costs of $9.93 
million are estimated using a 3 percent discount rate; present value 
costs of $69.2 million and annualized costs of $9.86 million are 
estimated using a 7 percent discount rate. Table 5 summarizes the 
quantified and non-quantified benefits and costs of extending oversight 
to IRBs unaffiliated with an institution holding an FWA.

Table 5--Summary of Estimated Benefits and Costs of Extending Oversight to IRBs Unaffiliated With an Institution
                           Holding an Federalwide Assurance (NPRM at Sec.   __.101(a))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Encouragement to institutions to rely on unaffiliated IRBs when appropriate.
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Developing IRB authorization                     84.6              69.2              9.93              9.86
     agreements.........................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------


[[Page 54001]]

c. Extending Common Rule Compliance Oversight to Clinical Trials 
Regardless of Funding Source (NPRM at Sec.  __.101(a)(2))
    The proposed rule would extend the regulations to cover clinical 
trials conducted at an institution in the United States that receives 
federal support from a Common Rule department or agency for non-exempt, 
non-excluded human subjects research, regardless of the funding source 
of the specific clinical trial. Extension of the rules would not apply 
to clinical trials already regulated by FDA.
    A small percentage of clinical trials currently are not subject to 
oversight by either the Common Rule or FDA regulations. This change in 
policy gives OHRP the authority to conduct oversight compliance of 
clinical trials not otherwise subject to human subjects protection 
regulations. The benefits to be gained in terms of equitable and just 
distribution of protections to all subjects of clinical trials warrant 
closing this gap in the current system. Moreover, while it is expected 
that this extension would apply to only a small percentage of clinical 
trials, they are the type of studies that often pose the greatest risks 
to subjects. Since this extension is expected to bring research that 
poses the most risk to research subjects under the rules, it is 
presumed that the current option in the FWA that allows institutions to 
voluntarily extend the funding Common Rule department or agency's 
compliance oversight authority to all research conducted at an 
institution regardless of funding source (i.e., ``checking the box'') 
would be unnecessary.
    Although more research would be covered by the policy, the 
extension is contingent on an entity receiving federal support for non-
exempt human subjects research; thus, the entity already should have an 
established IRB in place and would not incur costs establishing one or 
contracting with an unaffiliated IRB.
    The RIA estimates that there are 1,399 clinical trials currently 
not subject to oversight by either the Common Rule or FDA regulations. 
It is estimated that in 2016 all 1,399 of these clinical trials would 
undergo convened initial review. In subsequent years, an estimated 672 
protocols would undergo convened initial review, 502 would undergo 
convened continuing review, and 225 would undergo expedited continuing 
review based on the distribution of reviews presented in Table 3.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    Present value costs of $18.3 million and annualized costs of $2.15 
million are estimated using a 3 percent discount rate; present value 
costs of $15.1 million and annualized costs of $2.15 million are 
estimated using a 7 percent discount rate. Table 6 summarizes the 
quantified and non-quantified benefits and costs of oversight for 
clinical trials currently not subject to oversight.

   Table 6--Summary of Estimated Benefits and Costs of Extending Common Rule Compliance Oversight for Clinical
                        Trials Regardless of Funding Source (NPRM at Sec.   __.101(a)(2))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Improving institutional willingness to use unaffiliated IRBS, thereby facilitating the implementation of the
     proposed changes to Sec.   __.114 (Cooperative Research).
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Increase in number of reviews.......             18.3              15.1              2.15              2.15
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

d. Activities Excluded From the Requirements of the Common Rule Because 
They Are Not Research (NPRM at Sec.  __.101(b)(1))
    Six categories of activities would be excluded from the regulatory 
requirements of the Common Rule because they are not considered 
research as defined in Sec.  __.102(l) in the NPRM: (1) Certain data 
collection and analysis activities conducted for an institution's own 
internal operation and program improvement purposes; (2) certain 
activities that focus directly on the specific individuals about whom 
the information is collected (i.e., oral history, journalism, 
biography, and historical scholarship); (3) certain collection and 
analysis activities conducted by a criminal justice agency solely for 
criminal justice investigative purposes; (4) certain quality assurance 
or improvement activities; (5) certain public health surveillance 
activities; and (6) certain activities conducted by a defense, national 
security, or homeland security authority. The proposal in the NPRM to 
explicitly list certain activities that are not considered ``research'' 
for the purposes of this policy is not intended to suggest that these 
are the only six categories that may be considered not to meet the 
definition of ``research.''
    Federal agencies (and some institutions in the regulated community) 
engaged in activities considered in these exclusions already interpret 
such activities as excluded from the regulations. Thus, in general, the 
exclusions found in proposed Sec.  __.101(b)(1) represent a proposed 
codification of current practice. However, comments to the ANPRM 
suggested that at many institutions, activities that would now be 
explicitly excluded from the policy are being routinely reviewed by 
IRBs. While many

[[Page 54002]]

institutions are specifically creating policies to state that oral 
history or journalism activities do not require IRB review,\87\ 
institutions vary and some continue to require IRB review for other 
activities (such as quality improvement activities \88\) that may not 
meet the Common Rule's definition of research. Thus, explicitly 
excluding these six categories because they are to be considered not 
research would provide clarity to the regulatory community about what 
constitutes research per this policy, and also likely result in a 
modest decrease in the number of IRB reviews that occur each year in 
institutions.
---------------------------------------------------------------------------

    \87\ See e.g., Schrag, ZM ``Smithsonian Frees Oral History, 
Journalism, and Folklore,'' Institutional Review Blog, 30 July 2010, 
http://www.institutionalreviewblog.com/2010/07/smithsonian-frees-oral-history.html. See also ``More Universities Deregulate Oral 
History'', 7 April 2010, http://www.institutionalreviewblog.com/2010/04/more-universities-deregulate-oral.html.
    \88\ See e.g., Baily, MA ``Quality Improvement Methods in Health 
Care,'' in From Birth to Death and Bench to Clinic: The Hastings 
Center Bioethics Briefing Book for Journalists, Policymakers, and 
Campaigns, ed. Mary Crowley (Garrison, NY: The Hastings Center, 
2008), 147-152 http://www.thehastingscenter.org/Publications/BriefingBook/Detail.aspx?id=2204.
---------------------------------------------------------------------------

    Institutions, investigators, and IRBs involved in supporting, 
conducting, or reviewing these activities would no longer incur the 
costs of IRB review and approval and continuing review. Activities that 
were not intended to be subject to the regulations would clearly be 
excluded, allowing such activities to proceed without delays caused by 
the need for IRB submission, review, and approval.
    It is estimated that 6,754 annual reviews of protocols (1.0 
percent) would no longer be conducted as a result of the exclusions 
proposed in Sec.  __.101(b)(1). Of these reviews, 2,237 would have 
undergone convened initial review, 1,005 would have undergone expedited 
initial review, 2,423 would have undergone convened continuing review, 
and 1,089 would have undergone expedited continuing review based on the 
distribution of reviews presented in Table 3.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    Present value benefits of $74.0 million and annualized benefits of 
$8.67 million are estimated using a 3 percent discount rate, and 
present value benefits of $60.5 million and annualized benefits of 
$8.61 million are estimated using a 7 percent discount rate. Table 7 
summarizes the quantified and non-quantified benefits and costs of 
excluding these activities from the requirements of the Common Rule.

  Table 7--Summary of Estimated Benefits and Costs of Excluding Activities From the Requirements of the Common
                        Rule Because They Are Not Research (NPRM at Sec.   __.101(b)(1))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    Reduction in number of reviews......             74.0              60.5              8.67              8.31
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Increased clarity in what must be reviewed; ability for IRBs to focus efforts on reviews of higher-risk,
     more complex, research activities.
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

e. Low-Risk Research Activities Excluded From the Requirements of the 
Common Rule Because They Are Already Subject to Independent Controls 
(NPRM at Sec.  __.101(b)(2))
    The NPRM proposes that four additional categories of research 
activities be explicitly excluded from the regulatory requirements of 
the Common Rule because they are low-risk and already subject to 
independent controls in the absence of the protections of the Common 
Rule. These are: (1) Certain research activities that involve the use 
of certain educational tests, survey procedures, interview procedures, 
or observation of public behavior (a revised version of current 
exemption category 2); (2) certain research activities involving the 
collection or study of information (a revised version of current 
exemption category 4); (3) certain research activities conducted by a 
government agency using government-generated, non-research data; and 
(4) certain data collection and analysis activities using identifiable 
health information subject to the HIPAA Privacy Rule.
    The current Common Rule articulates two exemptions (current Rule at 
Sec.  __.101(b)(2) and (4)) that appear in a similar format in the 
proposed NPRM exclusions. Current Common Rule exemption category 2 is 
found in the NPRM in Sec.  __.101(b)(2)(i); current exemption category 
4 is found in NPRM Sec.  __.101(b)(2)(ii). In addition to being 
considered excluded from the rule (rather than exempt from certain 
requirements of the rule), current exemption category 2 (NPRM Sec.  
__.101(b)(2)(i)) has been clarified to state that interventions in 
conjunction with collection of data through the use of educational 
tests, survey procedures, interview procedures or observation of public 
behavior uninfluenced by the investigator (including visual or auditory 
recording) may not be used in research activities that qualify for this 
exclusion. For the research activities at issue in the NPRM at Sec.  
__.101(b)(2)(i), it is presumed that the activities poses little to no 
risk to subjects, and that the subjects knowingly and willingly

[[Page 54003]]

provide the information, or decline to participate. Thus, IRB review of 
the research and consent related documents are not believed to be 
necessary for such activities.
    Four changes are proposed to current exemption category 4 (NPRM at 
Sec.  __.101(b)(2)(ii)). First, the provision would now be considered 
excluded from the rule, not just exempt from certain requirements of 
the rule. Second, the provision no longer includes pathological 
specimens or diagnostic specimens. Third, NPRM Sec.  __.101(b)(2)(ii) 
removes the word ``existing'' from the provisions. This is intended to 
clarify the scope of the exclusion to allow for information that will 
be collected in the future. Finally, a condition is added requiring 
that the exclusion may only be used when the investigator has no plans 
to contact subjects, re-identify subject, or otherwise conduct an 
analysis that could lead to creating identifiable private information.
    Neither the exclusion at NPRM Sec.  __.101(b)(2)(iii) (certain 
research activities conducted by a government agency using government-
generated, non-research data) nor the exclusion at NPRM Sec.  
__.101(b)(2)(iv) (certain data collection and analysis activities using 
identifiable health information subject to the HIPAA Privacy Rule) 
appear in the current Rule. These research activities are excluded 
because human subjects are independently protected through other 
mechanisms or laws. It is anticipated that the exclusion of activities 
regulated by HIPAA as health care operation activities, public health 
activities, or research (NPRM at Sec.  __.101(b)(2)(iv)) would 
represent a significant reduction in the volume of activities an IRB 
reviews. For example, the proposed exclusion at Sec.  __.101(b)(2)(iv) 
would mean that at institutions subject to the HIPAA regulations, 
projects where one is simply analyzing protected health information 
from medical charts would not be required to undergo IRB review.
    Institutions, investigators, and IRBs involved in supporting, 
conducting, or reviewing these activities would no longer incur the 
costs of IRB review, approval, and continuing review. Activities that 
were not intended to be subject to the regulations would clearly be 
excluded, allowing such activities to proceed without delays caused by 
the need for IRB submission, review, and approval.
    The RIA estimates that 67,539 annual reviews of protocols (10.0 
percent) would no longer be conducted as a result of the proposed 
exclusions in Sec.  __.101(b)(2). It is anticipated that the exclusion 
of certain activities covered by the HIPAA Privacy Rule would drive the 
estimated reduction in annual IRB reviews of protocols. Of these 
reviews, 22,369 would have undergone convened initial review, 10,050 
would have undergone expedited initial review, 24,233 would have 
undergone convened continuing review, and 10,887 would have undergone 
expedited continuing review based on the distribution of reviews 
presented in Table 3.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    Present value benefits of $740 million and annualized benefits of 
$86.7 million are estimated using a 3 percent discount rate, and 
present value benefits of $605 million and annualized benefits of $86.1 
million are estimated using a 7 percent discount rate. Table 8 
summarizes the quantified and non-quantified benefits and costs of 
excluding these activities from the requirements of the Common Rule.

  Table 8--Summary of Estimated Benefits and Costs of Excluding Low-Risk Research From the Requirements of the
                                    Common Rule (NPRM at Sec.   __.101(b)(2))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    Reduction in number of reviews......              740               605              86.7              86.1
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Clarity in what research activities must be reviewed; ability for IRBs to focus efforts on reviews of higher-
     risk, more complex, research activities.
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

f. Clarifying and Harmonizing Regulatory Requirements and Agency 
Guidance (NPRM at Sec.  __.101(j)
    The proposed rule would require consultation among the Common Rule 
agencies for the purpose of harmonization of guidance, to the extent 
appropriate, before federal guidance on the Common Rule is issued, 
unless such consultation is not feasible. The proposal also recognizes 
that harmonization would not always be possible or desirable given the 
varied missions of the agencies that oversee the protection of human 
subjects and differences in statutory authorities. Note that this is a 
codification of harmonization efforts currently occurring across Common 
Rule agencies.
    This proposal appropriately recognizes the importance of harmonized 
guidance for the regulated community by creating, as much as possible, 
consistent interpretations of the regulations.
    There is no compliance requirement for the regulated community 
associated with this provision. It is anticipated that harmonization 
would create greater

[[Page 54004]]

uniformity in the regulatory requirements for investigators, 
institutions, and IRBs, which could reduce confusion and time spent 
complying with multiple sets of regulations. Costs for achieving 
harmonization would be borne by the Common Rule agencies.
    As this change likely would not impact staffing requirements at 
Common Rule agencies, no costs are quantified here. It is possible 
however, that the harmonization requirement could result in it taking 
longer for Common Rule agency guidance to be approved and issued to the 
public. Similarly, as it is unclear the extent to which this change 
would reduce the time IRBs spend on reviewing protocols, benefits are 
also not quantified. Table 9 summarizes the non-quantified benefits and 
costs of clarifying and harmonizing regulatory requirements and agency 
guidance.

   Table 9--Summary of Estimated Benefits and Costs of Clarifying and Harmonizing Regulatory Requirements and
                                   Agency Guidance (NPRM at Sec.   __.101(j))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Increased uniformity in regulatory requirements among Common Rule agencies; increased clarity to the
     regulated community about how regulations should be interpreted.
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    Time for consultation among Common Rule agencies before federal guidance is issued.
----------------------------------------------------------------------------------------------------------------

g. Expanding the Definition of Human Subject To Include Research 
Involving Non-Identified Biospecimens and Creating an Exemption for 
Secondary Research Using Biospecimens or Identifiable Private 
Information (NPRM at Sec. Sec.  __.102(e), __.101(b)(3)(i), and 
__.104(f)(2))
    The NPRM proposes to expand the definition of human subjects to 
include research in which an investigator obtains, uses, studies or 
analyzes a biospecimen. This would apply regardless of the 
identifiability of the biospecimen. Generally, investigators would not 
be allowed to remove identifiers from biospecimens without obtaining 
informed consent or a waiver of consent. Written consent would 
generally be required for such activities. Thus, this change will 
significantly expand the amount of research that is subject to the 
Common Rule. This requirement would not apply to biospecimens and 
information already collected at the time the final rule is published. 
Proposed Sec.  __.101(b)(3)(i) would exclude research activities 
involving non-identified biospecimens where no new information about an 
individual is generated. While activities such as developing new 
testing assays could be excluded under this provision, it is 
anticipated that under the NPRM proposals, most research with 
biospecimens would now fall under the Rule.
    At its core, this proposal is intended to promote the ethical 
principle of respect for persons. In addition to promoting respect for 
persons in the research enterprise, the proposed regulatory structure 
for research with biospecimens (whereby consent is sought for almost 
all research activities involving biospecimens) will encourage 
investigators to retain identifiers, which can enhance research by 
preserving the ability to link to important additional information 
about the subject. Additionally, members of the regulated community 
have reported situations where, even though not currently required by 
regulation, investigators were told by an IRB that they needed to 
obtain study-specific consent for research activities involving non-
identified biospecimens. Under the current NPRM proposals, such a 
situation would not occur because consent--be it broad or study 
specific--would always be obtained for research involving biospecimens.
    While this proposal will promote the ethical principle of respect 
for persons, it also will significantly increase the volume of studies 
for which investigators must seek and document informed consent (unless 
more stringent waiver criteria are met). The RIA estimates that there 
are 250,000 studies using biospecimens each year that are not currently 
subject to oversight by either the Common Rule or FDA regulations 
because they have been stripped of identifiers. Extrapolations from 
1999 data \89\ suggest that biospecimens are collected from as many as 
30 million individuals and are stored each year for both clinical and 
research purposes. Approximately 9 million individuals' biospecimens 
(30 percent) are collected for research purposes. As a conservative 
estimate, approximately 6.3 million individuals' biospecimens (30 
percent) could potentially be used in future research studies. Thus, it 
is possible that investigators would seek consent to secondary use of 
biospecimens or a waiver of consent for an additional 15 million 
individuals annually for secondary use of biospecimens.
---------------------------------------------------------------------------

    \89\ Eiseman, E., Haga, S. (1999). Handbook of Human Tissue 
Sources: A National Resource of Human Tissue Samples. Washington, 
DC: RAND Corporation.
---------------------------------------------------------------------------

    In the absence of comprehensive data, to calculate the number of 
protocols that will now be covered, two approaches are proposed; public 
comment is requested on these estimates and approaches. Under method 
one, it is estimated that approximately 50 biospecimens will be used on 
average per research protocol involving biospecimens. This gives a 
potential 300,000 new research protocols using

[[Page 54005]]

non-identified biospecimens. This estimate of 300,000 new research 
protocols is rounded down to 250,000 new studies because based on ANPRM 
comments and industry data, it seems reasonable to assume that, as a 
conservative estimate, the number of new biospecimen studies 
encapsulated by the proposed rule would equal the total number of new 
protocols conducted each year (i.e., the number of new biospecimen 
studies is likely close to the estimate of 246,382 new annual studies).
    Under method two, biospecimen repository representatives report 
that roughly 90 percent of their collections are used in non-identified 
form in research activities that do not fall under the current Common 
Rule. Thus, only 10 percent of biospecimen studies are currently 
covered by the Common Rule, representing a 9:1 ratio of studies 
involving non-identified biospecimens to studies involving identifiable 
biospecimens. Of the 246,382 new protocols each year that are non-
exempt (Table 3), we assume conservatively that 10-15 percent are using 
identifiable biospecimens. This equates to between 24,638 and 36,957 
new studies each year using identifiable biospecimens. As previously 
discussed, it is estimated that the number of biospecimen studies that 
occur on non-identified biospecimens each year is approximately 9 times 
the number of studies using identifiable biospecimens, or between 
221,741 and 332,613 studies each year. Thus, under method two, an 
estimate of 250,000 new studies on non-identified biospecimens each 
year is also reasonable.
    In order to facilitate research with biospecimens, the NPRM 
proposes to create separate elements of broad consent (NPRM at Sec.  
__.116(c), discussed in III.D.2.u below) such that investigators and 
institutions may seek, and individuals may grant, consent for future 
unspecified research activities. The NPRM also proposes an exemption 
that relies on obtaining broad consent for future, unspecified research 
studies (NPRM at Sec.  __.104(f)(2)). In order to be eligible for the 
exemption proposed in Sec.  __.104(f)(2), broad consent must have been 
sought and obtained using the Secretary's template for broad consent 
(described in proposed Sec.  __.116(d)(3)), and the investigator must 
not anticipate returning individual research results to subjects. To 
facilitate secondary research using biospecimens and identifiable 
private information, the NPRM also proposes an exemption for the 
storage and maintenance of biospecimens and identifiable private 
information for future, unspecified, secondary research activities 
(NPRM at Sec.  __.104(f)(1)), which is described in more detail in 
Section III.D.2.n below).
    The exemption proposed at Sec.  __.104(f)(2) is specifically for 
secondary research studies involving biospecimens and identifiable 
private information that have been or will be acquired for purposes 
other than the currently proposed research study. If a secondary 
research study does not meet the requirements of this exemption 
category, the investigator would need to seek IRB review of the study, 
and would need to obtain either study-specific consent or a waiver of 
informed consent under the Common Rule. Note that for biospecimens an 
IRB would apply the more stringent waiver criteria at proposed Sec.  
__.116(e)(2) or (f)(2). For identifiable private information, an IRB 
would apply the waiver criteria at proposed Sec.  __.116(e)(1) or 
(f)(1), which are almost identical to the waiver criteria in the 
current Common Rule.
    The proposed exemption at Sec.  __.104(f)(2), also ensures that in 
secondary research conducted with biospecimens or identifiable private 
information, appropriate privacy safeguards are in place (through 
requiring adherence to the privacy safeguards described in Sec.  
__.105). Thus, although this provision is an expansion in the nature of 
research that is exempt, it is accompanied by certain requirements and 
safeguards.
    It is anticipated that a majority of studies that utilize this 
exemption will be biospecimen studies. The extent to which individuals 
conducting secondary research studies involving identifiable private 
information will utilize this exemption is unknown given that there are 
additional pathways under this proposed rule to facilitate secondary 
research activities involving identifiable private information is 
unknown. To that end, the benefits and costs associated with this 
provision only take into consideration secondary research involving 
biospecimens. It is further anticipated that these revisions will 
result in higher value research with biospecimens being conducted with 
subjects' consent and without the need for full IRB review, or the need 
to go back to subjects to obtain consent for every secondary research 
study, as long as certain conditions are met.
    Because the estimated 250,000 biospecimen studies each year that 
will be newly covered under the rule as a result of the proposed 
modification to the definition of human subject will likely be low or 
minimal risk, the RIA assumes that all of these will be eligible for 
the Sec.  __.104(f)(2) exemption (so long as consent--broad or study 
specific--was sought and obtained). Benefits and costs associated with 
obtaining and tracking broad consent are discussed below in section 
III.D.2.u of this RIA. Because the compliance date for the expansion to 
the definition of human subject will be three years after the date of 
publication of a final rule, the benefits and costs described below 
assume a start date of 2019.
    As required under Sec.  __.104(c), an exemption determination must 
be made and documented for each of the 250,000 newly covered 
biospecimen studies. It is anticipated that in 50 percent of these 
studies (125,000 studies), investigators will spend 30 minutes entering 
information into the HHS-created decision tool in order for that tool 
to generate an exemption determination. In the remaining 125,000 
studies, it is anticipated that investigators will spend 30 minutes 
preparing and submitting information about the study to an individual 
able to make exemption determinations (per Sec.  __.104(c)). An 
individual at the IRB voting member level will spend an estimated 30 
minutes per study to make an exemption determination.
    In the absence of the proposed exempt category of research at Sec.  
__.104(f)(2) but taking into consideration the expansion to the 
definition of human subject, it is estimated that each year, all 
250,000 of these studies will undergo convened initial review. In 
subsequent years, it is estimated estimate that 120,000 protocols would 
undergo convened initial review, 89,700 would undergo convened 
continuing review, and 40,300 would undergo expedited continuing review 
based on the distribution of reviews presented in Table 3.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    Present value costs of $101 million and annualized costs of $11.9 
million are estimated using a 3 percent discount rate; present value 
costs of $77.8 million and annualized costs of $11.1 million are 
estimated using a 7 percent discount rate. Table 10 summarizes the 
quantified and non-quantified benefits and costs of amending the 
definition of human subject.

[[Page 54006]]



   Table 10--Summary of Expanding the Definition of Human Subject To Include Research Involving Non-Identified
    Biospecimens and Creating an Exemption for Secondary Research Using Biospecimens or Identifiable Private
                 Information (NPRM at Sec.  Sec.   __.102(e), __.101(b)(3)(i), and __.104(f)(2))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    Reduction in number of IRB reviews    ................  ................  ................  ................
     that would have otherwise occurred
     as a result of the expansion of the
     definition of human subject........
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Ethical benefit of respecting an individual's wishes in how his or her biospecimens are used in future;
     ensuring protection of human subjects in research activities involving non-identifiable biospecimens.
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Determining that these studies are                101              77.8              11.9              11.1
     exempt in accordance with Sec.
     __.104(c)..........................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    Potential reduction in number of biospecimens available for research........................................
----------------------------------------------------------------------------------------------------------------

h. Modifying the Assurance Requirements (current Rule at Sec.  
__.103(b)(1), (b)(3), (d))
    The NPRM proposes to modify the requirements of the assurance 
process in the following ways. First, the NPRM proposes to delete the 
requirement in the current Common Rule at Sec.  __.103(b)(1) of 
identifying a statement of principles governing all research at an 
institution. As discussed in section II.H.2 of this preamble, the 
requirement for institutions to designate a set of ethical principles 
to which that institution will abide in all research activities is 
generally not enforced. Further, for international institutions that 
may receive U.S. government funding for research activities, it creates 
the impression that these international institutions must modify their 
internal procedures to comport with the set of principles designated on 
the FWA for activities conducted at those institutions that receive no 
U.S. government funding. In order to provide clarity to these 
international institutions that such measures are not required for 
activities that receive no Common Rule department or agency support, 
this provisions has been deleted.
    The requirement that a written assurance include a list of IRB 
members for each IRB designated under the assurance would be replaced 
by the requirement that the assurance include a statement that for each 
designated IRB the institution, or when appropriate the IRB, prepares 
and maintains a current detailed list of the IRB members with 
information sufficient to describe each member's chief anticipated 
contributions to IRB deliberation; and any employment or other 
relationship between each member and the institution. The regulatory 
requirement at Sec.  __.103(b)(3) that changes in IRB membership be 
reported to the department or agency head, or to OHRP when the 
existence of an HHS-approved assurance is accepted, would be deleted, 
eliminating the requirement. Instead, an institution would be required 
under proposed Sec.  __.108(a)(2) to maintain a current IRB roster, but 
such a roster would not need to be submitted to OHRP or other agency 
managing the assurance of compliance process.
    The proposed changes to the IRB roster requirement are expected to 
reduce administrative burden and have the following additional 
beneficial effects, without having any significant impact on the 
protection of human subjects:
     Reduction in the administrative burdens on institutions 
related to the submission of IRB membership lists to OHRP and, in some 
cases, to the departments and agencies that process their own 
assurances;
     Reduction in the administrative burdens on OHRP with 
respect to reviewing and processing new and updated IRB membership 
lists as part of the IRB registration process, as well as reductions, 
in some cases, in the administrative burdens on other departments and 
agencies that receive and review IRB membership lists and changes in 
IRB membership as part of their own assurance processes;
     In some cases, reduction in the volume of records that 
need to be created and retained by the departments and agencies 
regarding the review and processing of IRB membership lists; and
     Simplification of the process for the electronic 
submission and acceptance of IRB registrations via the OHRP Web site.
    In addition, HHS anticipates modifying the FWA so that institutions 
would no longer have the option to ``check the box'' on an assurance 
and voluntarily extend the funding Common Rule department or agency's 
regulatory authority to all research conducted at an institution 
regardless of funding source. For research other than clinical trials, 
institutions could continue to voluntarily apply the regulations to all 
research conducted by the institution, but this voluntary extension 
would no longer be part of the FWA. Members of the regulated community 
report that whether or not they ``check the box'' on an assurance form, 
they tend to voluntarily apply the regulations to all research 
activities taking place at an institution regardless of funding. Thus, 
the removal of this option on an assurance form likely would not impact 
community practice. To that end, no costs have been associated with 
this provision.
    Finally, the current requirement at Sec.  __.103(d) that a 
department or agency head's evaluation of an assurance take into 
consideration the adequacy of the proposed IRB in light of the 
anticipated scope of the institution's activities and the types of 
subject populations likely to be involved, the appropriateness of the 
proposed initial

[[Page 54007]]

and continuing review procedures in light of the probable risks, and 
the size and complexity of the institution, would be deleted.
    The deletion of this provision would eliminate an administrative 
process that is no longer meaningful given the purpose and design of 
the FWA and OHRP's processes for reviewing IRB registrations and 
reviewing and approving FWAs. This change also harmonizes the Common 
Rule with FDA's human subjects protection regulations by eliminating 
the requirement to submit IRB membership lists.
    The RIA estimates that administrative staff at each IRB would spend 
5 fewer hours complying with the assurance requirements. Based on the 
estimates presented in Table 3, the dollar value of their time is 
calculated by multiplying hours by their estimated 2016-2025 wages and 
adjusting for overhead and benefits.
    Present value benefits of $5.81 million and annualized benefits of 
$0.68 million are estimated using a 3 percent discount rate; present 
value benefits of $4.10 million and annualized benefits of $0.58 
million are estimated using a 7 percent discount rate. Table 11 
summarizes the quantified and non-quantified benefits and costs of the 
proposed change to the IRB roster requirement.

  Table 11--Summary of Estimated Benefits and Costs of Proposed Change To Modifying the Assurance Requirements
                               (Current Rule at Sec.   __.103(b)(1), (b)(3), (d))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    Reduction in time for IRB                        5.81              4.10              0.68              0.58
     administrative staff and OHRP staff
     to submit, review, and process IRB
     membership lists...................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Reduction in volume of records created by an institution....................................................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

i. Requirement for Written Procedures and Agreements for Reliance on 
External IRBs (NPRM at Sec. Sec.  __.103(e) and __.115(a)(10))
    Language is proposed at Sec.  __.103(e) requiring each IRB, 
institution, or organization that has oversight responsibility for non-
exempt research involving human subjects covered by this policy and 
conducted by another institution to have a written agreement 
identifying the respective responsibilities of the IRB organization and 
the engaged institution for meeting the regulatory requirements of this 
policy. This is already a requirement under the terms of an FWA but 
this requirement increases the level of detail that has to be included 
in such agreements, specifically the roles and responsibilities of each 
party. In addition, a requirement is added at Sec.  __.115(a)(10) that 
institutions or IRBs retain the agreement between the institution and 
IRB specifying the responsibilities that each entity would undertake to 
ensure compliance with the requirements of proposed Sec.  __.103(e).
    The new requirements for agreements between institutions and 
external IRBs would not apply to research initiated before the 
effective date of the rule. However, the new requirements would affect 
existing agreements between institutions and external IRBs in cases 
where the existing agreements are not study-specific, but rather 
pertain to all research conducted by the institution or to a category 
or categories of human subjects research.
    Initially, costs would be involved in drafting, revising, and 
conducting managerial review of agreements to ensure they satisfy these 
new requirements. Anticipated benefits include enhanced protection of 
human subjects in research reviewed by nonaffiliated IRBs, and greater 
reliance on external IRBs as the IRB of record for cooperative 
research, as stipulated in proposed Sec.  __.114.
    Table 3 shows that there are 5,164 FWA-holding institutions without 
an IRB and 2,871 FWA-holding institutions with an IRB. We assume that 
the 5,164 FWA-holding institutions without an IRB have an average of 1 
IRB authorization agreement that would need to be modified as a result 
of the new requirements for agreements between institutions and 
external IRBs in 2016. In addition, we assume that the 2,871 FWA-
holding institutions with an IRB have an average of 0.20 IRB 
authorization agreements that would need to be modified in 2016. We 
estimate that each agreement would require an average of 10 hours of 
institution legal staff time and 5 hours of IRB administrator time to 
complete. The dollar value of their time is calculated by multiplying 
hours by their estimated 2016 wages and adjusting for overhead and 
benefits.
    Present value costs of $11.3 million and annualized costs of $1.32 
million are estimated using a 3 percent discount rate; present value 
costs of $10.8 million and annualized costs of $1.54 million are 
estimated using a 7 percent discount rate. Table 12 summarizes the 
quantified and non-quantified benefits and costs of the requirement for 
written procedures and agreements for reliance on external IRBs 
(Sec. Sec.  __.103(e) and __.115(a)(10) in the NPRM).

[[Page 54008]]



  Table 12--Summary of Requirement for Written Procedures and Agreements for Reliance on External IRBs (NPRM at
                                    Sec.  Sec.   __.103(e) and __.115(a)(10))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Enhanced human subjects protections in research reviewed by nonaffiliated IRBs and encouragement to
     institutions to rely on external IRBs when appropriate.....................................................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Time to modify written agreements                11.3              10.8              1.32              1.54
     between IRBs and institutions......
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

j. Eliminating the Requirement That the Grant Application Undergo IRB 
Review and Approval (Current Rule at Sec.  __.103(f))
    The proposed rule would eliminate the requirement in the current 
Rule at Sec.  __.103(f) that grant applications undergo IRB review and 
approval for the purposes of certification. As described in section 
II.h.2 of this preamble, the grant application is often outdated by the 
time the research study is submitted for IRB review and contains 
detailed information about the costs of a study, personnel, and 
administrative issues that go beyond the mission of the IRB to protect 
human subjects. Therefore, experience suggests that review and approval 
of the grant application is not a productive use of IRB time.
    Eliminating the requirement that the grant application undergo IRB 
review and approval would reduce administrative costs to investigators 
and IRB voting members. The proposed change likely would not reduce 
protections for human subjects or impose other costs.
    The RIA estimates that there are 324,187 initial reviews of 
protocols annually, of which 223,689 involve convened review and 
100,498 involve expedited review based on the distribution of reviews 
presented in Table 3. For the purpose of this analysis, it is assumed 
that each protocol reviewed by an IRB is associated with one grant 
application or other funding proposal. The RIA estimates that 
investigators spend an average of 15 minutes compiling their grant 
applications when they submit a protocol for initial review. Further, 
it is estimated that IRBs typically use two primary reviewers for 
convened review and one primary reviewer for expedited review, and that 
primary reviewers spend an average of 30 minutes reviewing the grant 
application. Based on the estimates in Table 3, the dollar value of 
their time is calculated by multiplying hours by their estimated 2016-
2025 wages and adjusting for overhead and benefits.
    Present value benefits of $310 million and annualized benefits of 
$36.3 million are estimated using a 3 percent discount rate, and 
present value benefits of $219 million and annualized benefits of $31.1 
million are estimated using a 7 percent discount rate. Table 13 
summarizes the quantified and non-quantified benefits and costs of 
eliminating the requirement that the grant application undergo IRB 
review and approval.

   Table 13--Summary of Estimated Benefits and Costs of Eliminating the Requirement That the Grant Application
                       Undergo IRB Review and Approval (Current Rule at Sec.   __.103(f))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    Decreased time associated with                    310               219              36.3              31.1
     review.............................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------


[[Page 54009]]

k. Tracking and Documenting Exemption Determinations (NPRM at 
Sec. Sec.  __.104(c) and __.115(a)(11))
    New in the NPRM is a proposal at Sec.  __.104(c) that Federal 
departments and agencies would develop an exemption determination tool 
for use by investigators and institutions. Under the proposed rule, 
unless otherwise required by law, exemption determinations may be made 
by (1) an individual who is knowledgeable about the exemption 
categories and who has access to sufficient information to make an 
informed and reasonable determination, or (2) the investigator who 
accurately inputs information into the federally created web-based 
decision tool (NPRM at Sec.  __.104(c)). Also new in the NPRM is a 
requirement at proposed Sec.  __.115(a)(11) that an IRB maintain 
records of exemption determinations. Additionally, proposed Sec.  
__.104(c) specifies that the use of the exemption determination tool 
would satisfy the documentation requirement in proposed Sec.  
__.115(a)(11).
    While the documentation requirement for exemption determinations is 
new, comments from members of the regulated community suggest that most 
institutions have systems in place already to make and document 
exemption determinations. Thus, the requirement of proposed Sec.  
__.115(a)(11) would likely have a negligible impact on institutions. 
Additionally, it is anticipated that use of the exemption determination 
tool described in proposed Sec.  __.104(c) would likely represent a 
reduction in burden for institutions and investigators. First, 
institutions are not responsible for creating the decision tool; the 
Federal Government is. The costs associated with the development and 
maintenance of this tool are discussed above in section III.D.2.a of 
this RIA. Second, except for protocols for which IRB review is required 
by law and those for which the exemption tool is unable to issue 
determinations (and therefore still have to be submitted to an IRB for 
review), IRB offices would no longer need to devote significant 
resources to processing and reviewing studies for exemption because the 
use of the tool by the investigator would suffice. Third, the 
investigator would no longer need to engage in the time-intensive task 
of developing and submitting a formal application to an IRB for an 
exemption determination, which is standard practice at many 
institutions. Instead, the investigator would be able to answer 
questions in the to-be-created tool, and then be able to commence work 
if determination generated by the tool indicates that the proposed 
research activity meets one of the exemption categories.
    The quantifiable benefits and costs associated with the use of the 
Sec.  _.104(c) decision tool are documented in each RIA discussion of 
exemption categories (sections II.D.2.f, l, m, n of this RIA). Note 
that while Sec.  _104(c) requires that an exemption determination be 
made before an exempt study may begin, the use of the proposed 
exemption determination tool is not mandated. Rather, the tool to be 
created by HHS is an option proposed in order to reduce burden on the 
investigators and institutions. Additionally, note that at present it 
is unknown how many studies are exempted under the current Rule each 
year. Thus, this RIA is only able to provide quantifiable benefits and 
costs for studies that are estimated to be newly exempted.
    Table 14 summarizes the non-quantified benefits and costs of the 
tracking requirements for exemption determinations and the criteria for 
those eligible to make exemption decisions in NPRM Sec.  _.104(c).

 Table 14--Summary of Estimated Benefits and Costs of Tracking and Documenting Exemption Determinations (NPRM at
                                    Sec.  Sec.   __.104(c) and __.115(a)(11))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Reduced administrative burden for IRBs in reviewing exemption determinations, reduced time for investigators
     to receive an exemption determination......................................................................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

    l. Exemption for Research and Demonstration Projects (NPRM at Sec.  
_.104(d)(2))
    The current exemption related to research and demonstration 
projects (current Rule at Sec.  _.101(b)(5)) would be revised to 
clarify that certain Common Rule agency or department supported 
activities currently fall within that scope. OHRP also proposes to 
broaden its interpretation of public benefit and service programs which 
are being evaluated as part of the research to include public benefit 
or service programs that an agency does not itself administer through 
its own employees or agents, but rather funds (i.e., supports) through 
a grant or contract program. It has been OHRP's interpretation that the 
current exemption category 5 only applies to those research and 
demonstration projects designed to study a ``public benefit or service 
program'' that a Common Rule agency or department itself administers, 
and for which the public benefit or service program exists independent 
of any research initiative.
    The proposed regulatory revision and change in OHRP's 
interpretation of the exemption is designed to clarify and broaden the 
scope of the exemption so that more research studies would be exempt. 
It is believed that these changes would make the exemption easier to 
apply appropriately and is expected to

[[Page 54010]]

reduce the number of studies that would be required to undergo IRB 
review. It is also designed to allow the Federal Government to carry 
out important evaluations of its public benefit and service programs to 
ensure that those programs are cost effective and deliver social goods 
without requiring IRB review and approval. The proposed changes to this 
exemption would require OHRP to revise its existing guidance document 
on this exemption accordingly. Costs associated with this revision are 
accounted for in section III.D.2.a above.
    In addition, a requirement has been added that each Federal 
department or agency conducting or supporting the research and 
demonstration projects must establish on a publicly accessible federal 
Web site or in such other manner as the Secretary of HHS may prescribe, 
a list of the research and demonstration projects which the Federal 
department or agency conducts or supports under this provision. The 
research or demonstration project must be published on this list prior 
to or upon commencement of the research. This exemption is needed for 
government entities to carry out activities related to their important 
public health mission and functions; in acknowledgement of the fact 
that more-than-minimal-risk studies could be conducted under this 
exemption, the posting requirement promotes increased transparency in 
these activities.
    Note that a study's exemption documentation requirement at Sec.  
_.104(c) is satisfied by a Federal department or agency posting minimal 
information about the research or demonstration project on a federal, 
publicly accessible Web site. Thus, in general, an institutional 
official would not have to post any information to this Web site.
    It is estimated that approximately 1,000 exempt research and 
demonstration studies are currently conducted each year.\90\ It is 
further estimated that due to the change in OHRP's interpretation of 
the research and demonstration project exemption, an additional 3,377 
annual reviews of protocols (0.5 percent) would no longer be conducted. 
Of these 3,377 reviews, 1,118 would have undergone convened initial 
review, 502 would have undergone expedited initial review, 1,212 would 
have undergone convened continuing review, and 544 would have undergone 
expedited continuing review based on the distribution of reviews 
presented in Table 3. Comment is requested on the accuracy of the 
estimates of the number of research and demonstration projects 
conducted each year.
---------------------------------------------------------------------------

    \90\ Estimates based on queries of clinicaltrials.gov and a 
search of the CMS Web site. See e.g., http://www.medicaid.gov/medicaid-chip-program-information/by-topics/waivers/waivers_faceted.html, and https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/ActiveProjectReports/APR_2011_Edition.html.
---------------------------------------------------------------------------

    The 4,377 estimated annual studies conducted under this exemption 
would need to be posted to a federal Web site as required by Sec.  
_.104(d)(2)(i). It is anticipated that it would take individuals at the 
IRB administrative staff level 15 minutes per study to post the study 
to the Web site. Note that costs related to developing the Web site to 
which information about demonstration projects would be posted are 
calculated in section III.D.2.a of this RIA.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    Present value benefits of $37.0 million and annualized benefits of 
$4.34 million are estimated using a 3 percent discount rate, and 
present value benefits of $30.3 million and annualized benefits of 
$4.31 million are estimated using a 7 percent discount rate. Present 
value costs of $0.36 million and annualized costs of $0.04 million are 
estimated using a 3 percent discount rate; present value costs of $0.30 
million and annualized costs of $0.04 million are estimated using a 7 
percent discount rate. Table 15 summarizes the quantified and non-
quantified benefits and costs of amending an exempt category.

 Table 15--Summary of Estimated Benefits and Costs of Amending the Research and Demonstration Project Exemption
                                          (NPRM at Sec.   __.104(d)(2))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    Reduction in the number of studies               37.0              30.3              4.34              4.31
     requiring IRB review...............
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Reduction in time to determine whether the exemption applies to research and demonstration studies;
     increased transparency to the public in the types of research activities conducted under this exemption....
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Communication of the exempt research             0.36              0.30              0.04              0.04
     and demonstration studies..........
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    Possible delays in commencement of exempt research and demonstration studies until posting has occurred;
     revising federal guidance documents........................................................................
----------------------------------------------------------------------------------------------------------------


[[Page 54011]]

m. Expansion of Research Activities Exempt From IRB Review (NPRM at 
Sec.  __.104(d)(3), (e)(1), (e)(2))
    Three proposed exemptions in the NPRM would expand the types of 
activities that could occur without any IRB review (expedited or full-
board). A new exemption at proposed Sec.  __.104(d)(3) covers research 
involving benign interventions in conjunction with the collection of 
data from an adult subject through verbal or written responses 
(including data entry) or video recording if the subject prospectively 
agrees to the intervention and data collection and at least one of two 
criteria is met.
    A second exemption at proposed Sec.  __.104(e)(1) covers research 
involving the use of educational tests (cognitive, diagnostic, 
aptitude, achievement), survey procedures, interview procedures or 
observation of public behavior (including visual or auditory 
recording), if the information obtained is recorded in such a manner 
that human subjects can be identified directly or through identifiers 
linked to the subjects. A third exemption at proposed Sec.  
__.104(e)(2) would permit the secondary research use of identifiable 
private information originally collected for non-research purposes, so 
long as notice was provided to the prospective human subjects about the 
research activities and the identifiable private information is used 
only for purposes of the specific research for which the investigator 
or recipient entity obtained the information.
    Because the new exemptions at Sec.  __.104(e)(1) and (2) permits 
investigators to record potentially sensitive information about 
research subjects in an identifiable form, such activities must comply 
with the privacy safeguards found at Sec.  __.105 in the proposed Rule. 
Some of this research may be eligible for expedited review under the 
current rule, and would now be exempt from even that level of IRB 
review under the proposed rule. This would result in costs savings 
associated with IRB submission, review, and approval. In addition, most 
institutions already have information protection systems and policies 
in place and are likely to already meet the privacy safeguards of 
proposed Sec.  __.105.
    It is estimated that 6,754 annual reviews of protocols (0.5 
percent) would no longer be conducted as a result of these proposed 
changes. Of these reviews, 2,236 would have undergone convened initial 
review, 1,004 would have undergone expedited initial review, 2,424 
would have undergone convened continuing review, and 1,088 would have 
undergone expedited continuing review based on the distribution of 
reviews presented in Table 3.
    As required under Sec.  __.104(c), an exemption determination must 
be made and documented for each of these 6,754 newly exempted studies. 
It is anticipated that in 50 percent of these studies (3,377 studies), 
investigators will spend 30 minutes entering information into the HHS-
created decision tool in order for that tool to generate an exemption 
determination. In the remaining 3,377 studies, it is anticipated that 
investigators will spend 30 minutes preparing and submitting 
information about the study to an individual able to make exemption 
determinations (per Sec.  __.104(c)). An individual at the IRB voting 
member level will spend an estimated 30 minutes per study to make an 
exemption determination.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    The estimated costs associated with new privacy and security 
standards are presented section III.D.2.o of this RIA. Present value 
benefits of $70.0 million and annualized benefits of $8.20 million are 
estimated using a 3 percent discount rate, and present value benefits 
of $57.2 million and annualized benefits of $8.16 million are estimated 
using a 7 percent discount rate. Table 16 summarizes the quantified and 
non-quantified benefits and costs of modifying the exemption categories 
for research involving adults.

      Table 16--Summary of Estimated Benefits and Costs of Creating New Exemption Categories (NPRM at Sec.
                                         __.104(d)(3), (e)(1), (e)(2)))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    Reduction in number of reviews......             70.0              57.2              8.20              8.16
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------


[[Page 54012]]

n. Exemption for the Storage and Maintenance of Biospecimens and 
IdentPrivate Information for Future, Unspecified Secondary Research 
Activities After Consent Has Been Sought and Obtained (NPRM at 
Sec. Sec.  __.104(f)(1) and __.111(a)(9))
    The NPRM proposes a specific exemption for storage and maintenance 
of biospecimens (regardless of identifiability) and identifiable 
private information for future, unspecified secondary research 
activities after consent has been sought and obtained. The idea behind 
this exemption is that an institution can store and maintain 
biospecimens and identifiable private information for future research 
studies without being required to have a specific repository creation 
protocol developed, reviewed, and approved by an IRB. To be eligible 
for the exemption, the institution or an investigator must seek broad 
consent for the future use of biospecimens and information using the 
Secretary's broad consent template. Biospecimens and identifiable 
private information from both the research or non-research contexts may 
be designated under this exemption for future unspecified research 
studies. As part of the condition for this proposed exemption, an IRB 
would be required to do a one-time, limited review of the consent 
process using the expedited review procedure (as would be required in 
proposed Sec.  _ _.111(a)(9)). The privacy safeguards outlined in 
proposed Sec.  _ _.105 would apply to these activities. Note that if 
moving the biospecimens or information collected for use in future 
unspecified research studies is envisioned, as part of the limited IRB 
review described in Sec.  _ _.111(a)(9), an IRB would also need to 
review the adequacy of the privacy safeguards described in Sec.  _ 
_.105.
    Non-quantified benefits of this provision include clearer 
instructions to the regulated community about the extent to which 
creating system for storing and maintaining biospecimens and 
identifiable private information for future, unspecified secondary 
research activities is governed by this rule. Additionally, by reducing 
the IRB burden associated with approving this type of activity, this 
provision also incentivizes the creation of institution-wide, 
comprehensive systems for the storage and maintenance of biospecimens 
and identifiable private information for future, unspecified secondary 
research activities, which would foster more research while remaining 
respectful of subject autonomy. Because of the benefits to 
investigators of being eligible for a new exemption if secondary 
research activities are conducted using biospecimens or identifiable 
private information maintained or stored according to Sec.  _ 
_.104(f)(1), institutions would be further incentivized to implement 
and develop such a system. Also note that while FDA is unable to 
harmonize with the Common Rule on many of the exemptions due to 
specific requirements in FDA's authorizing statutes, including the 
Sec.  _ _.104(f)(2) exemption, research that is also subject to the FDA 
regulations would be eligible for this exemption.
    Because of the proposal for the rule to cover all biospecimens 
regardless of identifiability, it is anticipated that a majority of 
institutions would elect to develop a system for storing and 
maintaining biospecimens and identifiable private information for 
future, unspecified secondary research activities as allowed under the 
proposed exemption at Sec.  _ _.104(f)(1). This RIA estimates that 
6,428 FWA holding institutions (80 percent) would develop such a 
mechanism for storing and maintaining biospecimens and identifiable 
private information for future, unspecified secondary research 
activities. The RIA anticipates that 1,607 FWA institutions (20 
percent) would not develop this type of mechanism, either due to the 
lower volume of research overall conducted at that institution or 
because the institution conducts mostly social and behavioral research. 
At each of the 6,428 institutions where a storage and maintenance 
schema exemptible under NPRM Sec.  _ _.104(f)(1) is developed, it is 
assumed that an individual at the IRB administrator level would spend 
two hours at each institution reviewing the consent process through 
which a subject's broad consent to future research uses of his or her 
biospecimens or information is sought.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    Present value costs of $1.58 million and annualized benefits of 
$0.19 million are estimated using a 3 percent discount rate, and 
present value benefits of $1.48 million and annualized benefits of 
$0.21 million are estimated using a 7 percent discount rate. Table 17 
summarizes the quantified and non-quantified benefits and costs of 
modifying the exemption categories for research involving adults.

  Table 17--Exemption for the Storage and Maintenance of Biospecimens and Identifiable Private Information for
Future, Unspecified Secondary Research Activities After Consent Has Been Sought and Obtained (NPRM at Sec.  Sec.
                                          __.104(f)(1) and __.111(a)(9))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Fostering research with biospecimens and identifiable private information...................................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs

[[Page 54013]]

 
    Obtaining limited IRB review of                  1.58              1.48              0.19              0.21
     consent process....................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

o. Privacy Safeguards for Biospecimens and Identifiable Private 
Information (NPRM at Sec. Sec.  __.105 and __.115(c))
    Increasing research use of genetic information, information 
obtained from biospecimens, medical records, and administrative claims 
data has altered the nature of the risks to those whose information is 
being used in research. The risks related to these types of research 
are not physical but rather are informational through, for example, the 
unauthorized release or use of information about subjects. Currently, 
IRBs evaluate each study with regard to all levels of risk and are 
expected to determine whether the privacy of subjects and the 
confidentiality of their information is protected. Under the current 
Common Rule, IRBs must review each individual study's protection plan 
to determine whether it is adequate with respect to the informational 
risks of that study.
    The proposed rule would impose a new requirement that institutions 
and investigators implement appropriate security safeguards for 
biospecimens and identifiable private information. The purpose of these 
safeguards is to assure that access to biospecimens and individually 
identifiable private information is only authorized in appropriate 
circumstances and that informational risks are managed by applying 
appropriate safeguards to information and biospecimens. To ensure that 
the requisite limitations on use and disclosure are met, an institution 
or investigator can obtain adequate assurances through the use of a 
written agreement with the recipient of the information or 
biospecimens. In addition, a new provision is proposed at Sec.  
__.115(c) that requires that the institution or IRB retaining IRB 
records shall safeguard, if relevant, individually identifiable private 
information contained in those records in compliance with the privacy 
safeguards proposed at Sec.  __.105.
    Under the proposal, the HHS Secretary would develop a set of 
minimum standards for the protection of information for research 
outside of the current scope of the HIPAA standards to create an 
effective and efficient means of implementing appropriate protections 
for biospecimens and information. This list would be developed in 
consultation with other Common Rule agencies and would be published in 
the Federal Register.
    Consequently, the IRBs would not be required to review the 
individual plans for safeguarding information and biospecimens for each 
research study, so long as investigators would adhere to one or the 
other set of standards. It is anticipated that once IRBs are familiar 
with standard institutional- and investigator-imposed protections they 
would become more comfortable with the fact that they need not review 
every protocol for security standards. In addition, IRBs would not have 
to review security provisions on a case-by-case basis, which would 
result in cost savings in terms of time.
    It is expected that most research institutions would already have 
most of these protections in place, especially those institutions that 
are subject in whole or part to the HIPAA rules. Other fiduciary, 
legal, and proprietary responsibilities related to obtaining and 
storing biospecimens are likely to encompass the protections proposed 
for securing biospecimens. Also note that the envisioned security 
measures that will appear on the Secretary's List would be less 
stringent than what many institutions have already implemented. It 
should also be noted that the NPRM proposal would result in uniform 
baseline standards for security. Costs associated with developing the 
Secretary's List in accordance with proposed Sec.  __.105 are accounted 
for in section III.D.2.a of this RIA.
    It is estimated that 803 of the 8,035 institutions with FWAs (10 
percent) would need to update their privacy and security standards to 
comply with the new requirements. At these institutions, institutional 
officials and institutional legal staff would each spend an estimated 
80 hours in 2016 and 20 hours in subsequent years to update and monitor 
their privacy and security standards. In addition, the RIA estimates 
that 43,997 of 439,968 investigators (10 percent) would be required to 
adopt the updated privacy and security standards. These investigators 
would each spend an 40 hours in 2016 and 10 hours in subsequent years 
to comply. Based on the estimates presented in Table 3, the dollar 
value of their time is calculated by multiplying hours by their 
estimated 2016-2025 wages and adjusting for overhead and benefits. 
Public comments are requested on these estimates.
    Present value costs of $457 million and annualized costs of $53.6 
million are estimated using a 3 percent discount rate; present value 
costs of $347 million and annualized costs of $49.4 million are 
estimated using a 7 percent discount rate. Table 18 summarizes the 
quantified and non-quantified benefits and costs to protect information 
and biospecimens.

[[Page 54014]]



  Table 18--Summary of Estimated Benefits and Costs of Protection of Information and Biospecimens (NPRM at Sec.
                                          Sec.   __.105 and __.115(c))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Improved protection of individually identifiable private information and biospecimens.......................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs                                      457               347              53.6              49.4
----------------------------------------------------------------------------------------------------------------
    Time for institutions to update and adopt new privacy and security standards................................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

p. Elimination of Continuing Review of Research under Specific 
Conditions (NPRM at Sec. Sec.  __.109(e), (f) and __.115(a)(3), (8))
    The NPRM proposes eliminating continuing review for many minimal 
risk studies, unless the reviewer explicitly justifies why continuing 
review would enhance protection of research subjects. For studies 
initially reviewed by a convened IRB, continuing review would not be 
required, unless specifically mandated by the IRB, after the study 
reaches the stage where it involves one or both of the following: (1) 
Analyzing data (even if it is identifiable private), or (2) accessing 
follow-up clinical data from procedures that subjects would undergo as 
part of standard care for their medical condition or disease. If an IRB 
chooses to conduct continuing review even when these conditions are 
met, the rationale for doing so must be documented according to a new 
provision at Sec.  __.115(a)(3).
    It is also proposed that continuing review of research eligible for 
expedited review in accordance with Sec.  __.110 not be required, 
although an IRB may determine that continuing review of research 
eligible for expedited review is necessary. When an IRB requires 
continuing review of such studies, this too must be documented in 
compliance with a proposed requirement at Sec.  __.115(a)(8).
    Requiring continuing review for studies that are minimal risk (and 
eligible for expedited review at the onset) or that no longer pose 
greater than minimal risk presents a regulatory burden that does not 
meaningfully enhance protection of subjects. Further, the requirement 
takes time from the IRB's review of higher risk studies.
    This would result in less time spent by institutions, IRBs, and 
investigators in terms of time spent preparing for and conducting 
continuing review. This is a one-time compliance burden in Year 1 for 
institutions to update their systems to no longer send continuing 
review reminders to certain investigators. There would be increased 
recordkeeping requirements, however, for institutions to comply with 
Sec.  __115(a)(3) and (a)(8). Because we estimate that 90 percent of 
protocols that previously had to undergo continuing view would no 
longer need to, there is an overall net benefit. However, 10 percent of 
studies would require a new recordkeeping component. The benefits in 
terms of cost savings would begin in year one and extend indefinitely. 
However, costs would be associated with the requirement that IRBs 
document cases in which they elect to conduct continuing review when it 
is not a regulatory requirement.
    The RIA estimates that there are 108,873 expedited continuing 
reviews of protocols annually based on the distribution of reviews 
presented in Table 3. Of these reviews, the RIA further estimates that 
81,546 reviews (75 percent) would not be eliminated by other proposed 
changes to the Common Rule (such as the modifications proposed at 
Sec. Sec.  __.101(b); __.104(d)(1)-(3), (e)(1), and (f)). It is 
estimated that 40,773 of these 81,546 reviews (50 percent) would be 
discontinued and the remaining 40,773 reviews (50 percent) would 
continue and require documentation of the rationale for doing so. The 
RIA also estimates that IRB voting members would spend 1 hour per 
review providing documentation. In addition, administrative staff at 
each IRB would spend an estimated 10 hours in 2016 updating their 
communication systems to no longer send continuing review reminders to 
certain investigators.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    Present value benefits of $145 million and annualized benefits of 
$17.0 million are estimated using a 3 percent discount rate, and 
present value benefits of $119 million and annualized benefits of $16.9 
million are estimated using a 7 percent discount rate. Present value 
costs of $38.8 million and annualized costs of $4.55 million are 
estimated using a 3 percent discount rate; present value costs of $31.9 
million and annualized costs of $4.54 million are estimated using a 7 
percent discount rate. Table 19 summarizes the quantified and non-
quantified benefits and costs of the elimination of continuing review 
of research under specific conditions.

[[Page 54015]]



   Table 19--Summary of Estimated Benefits and Costs of the Elimination of Continuing Review of Research Under
                 Specific Conditions (NPRM at Sec.  Sec.   __.109(e), (f) and __.115(a)(3), (8))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits                                   145               119              17.0              16.9
    Reduction in number of continuing
     reviews............................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Time to document rationale for                   38.8              31.9              4.55              4.54
     conducting continuing review and
     update IRB communication systems...
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

q. Expedited Review Procedures (NPRM at Sec. Sec.  __.110 and 
__.115(a)(9))
    The proposed rule would make minor changes regarding expedited 
review, to change the default position such that expedited review can 
occur for studies on the HHS Secretary's list unless the reviewer(s) 
determine(s) that the study involves more than minimal risk. The NPRM 
also proposes that, in consultation with other Common Rule departments 
or agencies, the expedited review categories be reviewed every eight 
years and amended as appropriate, followed by publication in the 
Federal Register and solicitation of public comment. Finally, there 
would be a new requirement at proposed Sec.  __.115(a)(9) concerning 
IRB records that IRBs document the rationale for an expedited 
reviewer's determination that research appearing on the expedited 
review list is more than minimal risk (i.e., an override of the 
presumption that studies on the Secretary's list are minimal risk). 
Additionally, in order to assist institutions in determining whether an 
activity is minimal-risk, the NPRM proposes in Sec.  __.102(j) that the 
Secretary of HHS will maintain guidance that includes a list of 
activities considered to be minimal risk. The costs associated with 
developing and maintaining this guidance document are accounted for 
above in III.D.2.a of this RIA.
    The proposed changes to the expedited review procedures are 
expected to reduce the IRB workload by increasing the number of studies 
that undergo expedited review rather than convened review. The 
documentation requirement does not produce additional requirements 
because IRBs must keep records of determinations regardless. This just 
stipulates that the reason for an override must be described. However, 
costs would be associated with the requirement that IRBs document cases 
in which they elect to conduct convened IRB review when it is not a 
regulatory requirement.
    It is estimated that there are 223,689 convened initial reviews and 
242,330 convened continuing reviews of protocols annually based on the 
distribution of reviews presented in Table 3. Of these 223,689 convened 
initial reviews, it is estimated that 2,237 reviews (1 percent) are 
eligible for expedited review because they are in a category of 
research that appears on the HHS Secretary's list. Of these 2,237 
reviews, it is estimated that 1,118 reviews (50 percent) would undergo 
expedited review and the remaining 1,118 reviews (50 percent) would 
undergo convened review and require documentation of the rationale for 
doing so.
    Of the 242,330 convened continuing reviews, it is estimated that 
2,423 reviews (1 percent) are eligible for expedited review because 
they are in a category of research that would appear on the Secretary's 
list. Of these 2,423 reviews, the RIA estimates that 1,212 reviews (50 
percent) would undergo convened review and would require documentation 
of the rationale for doing so. Due to the proposed elimination of 
continuing review of research under specific conditions (Sec.  
__.109(e) and (f); Sec.  __.115(a)(3) and (a)(8)), the remaining 1,212 
reviews (50 percent) would not require review. Of these 1,212 reviews, 
the RIA estimates that 606 reviews (50 percent) would not occur and the 
remaining 606 reviews (50 percent) would undergo expedited continuing 
review and require documentation of the rationale for doing so. The RIA 
estimates that IRB voting members would spend 1 hour per review 
providing documentation when required. The cost associated with 
reviewing and amending the list is accounted for in section III.D.2.a 
of this RIA.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    Present value benefits of $16.8 million and annualized benefits of 
$1.97 million are estimated using a 3 percent discount rate, and 
present value benefits of $13.7 million and annualized benefits of 
$1.95 million are estimated using a 7 percent discount rate. Present 
value costs of $2.71 million and annualized costs of $0.32 million are 
estimated using a 3 percent discount rate; present value costs of $2.21 
million and annualized costs of $0.32 million are estimated using a 7 
percent discount rate. Table 20 summarizes the quantified and non-
quantified benefits and costs of the elimination of expedited review 
procedures.

[[Page 54016]]



   Table 20--Summary of Estimated Benefits and Costs of Amending the Expedited Review Procedures (NPRM at Sec.
                                         Sec.   __.110 and __.115(a)(9))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits                                  16.8              13.7              1.97              1.95
    Reduction in number of reviews......
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Time to document rationale for                   2.71              2.21              0.32              0.32
     conducting expedited review........
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

r. Revised Criteria for IRB Approval of Research (NPRM at Sec.  __.111)
    Two changes are proposed in the criteria for IRB approval of 
research. One pertains to the new requirements proposed at Sec.  __.105 
to protect biospecimens and individually identifiable private 
information used in research. The regulations at Sec.  __.111(a)(7) 
currently require that in order to approve research covered by this 
policy, the IRB shall determine that when appropriate, there are 
adequate provisions to protect the privacy of subjects and to maintain 
the confidentiality of data. This requirement would be modified to 
recognize that the requirements at Sec.  __.105 would apply to all non-
exempt research (unless the criteria for exemptions are met). The 
default position should be that if the provisions at Sec.  __.105 are 
being met, there is no need for additional IRB review of a research 
study's privacy and confidentiality protections. However, there might 
be extraordinary cases in which an IRB determines that privacy 
safeguards above and beyond those called for in Sec.  __.105 are 
necessary. Therefore, it is proposed that IRBs would be responsible for 
ensuring there are adequate provisions to protect the privacy of 
subjects and to maintain the confidentiality of data only if the IRB 
determines that the protections required in Sec.  __.105 are 
insufficient.
    The second proposed change relates to the new exemption at Sec.  
__.104(f)(2) that includes a criterion at (f)(2)(ii) that the 
exemptions do not apply if the investigator intends to return 
individual research results to subjects. Thus, a new provision would be 
added at Sec.  __.111(a)(8) clarifying that IRBs need to review any 
plan in a research protocol for returning individual research results 
to subjects and to determine whether it is appropriate. Although many 
IRBs probably already review plans for return of results, and many 
studies do not include this feature, it would not be required that IRBs 
review all projects to determine if there should be a plan.
    The RIA estimates that there are 324,187 initial reviews of 
protocols annually, of which 223,689 involve convened review and 
100,498 involve expedited review based on the distribution of reviews 
presented in Table 3. The RIA estimates that IRBs typically use two 
primary reviewers for convened review and one primary reviewer for 
expedited review, and that primary reviewers spend an average of 15 
minutes reviewing the security plans for biospecimens or identifiable 
private information. Of the 324,187 initial reviews, we estimate that 
108,062 reviews (33 percent) would include a plan for returning results 
to subjects and that primary reviewers would spend an average of 15 
minutes reviewing these plans. Based on the estimates in Table 3, the 
dollar value of their time is calculated by multiplying hours by their 
estimated 2016-2025 wages and adjusting for overhead and benefits.
    Present value benefits of $126 million and annualized benefits of 
$14.8 million are estimated using a 3 percent discount rate, and 
present value benefits of $89.1 million and annualized benefits of 
$12.7 million are estimated using a 7 percent discount rate. Present 
value costs of $66.6 thousand and annualized costs of $7.8 thousand 
using a 3 percent discount rate; present value costs of $62.3 thousand 
and annualized costs of $8.9 thousand using a 7 percent discount rate. 
Table 21 summarizes the quantified and non-quantified benefits and 
costs of the revised criteria for IRB approval of research.

Table 21--Summary of Estimated Benefits and Costs of Revised Criteria for IRB Approval of Research (NPRM at Sec.
                                                      __.111)
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    Decreased time associated with each               126              89.1              14.8              12.7
     review.............................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Increased opportunities for research subjects to learn the results of studies in which they participated....
----------------------------------------------------------------------------------------------------------------

[[Page 54017]]

 
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Time to review plans for returning               0.07              0.06             0.008             0.009
     results to subjects................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

s. Cooperative Research (NPRM at Sec. Sec.  __.114, __.103(e), and 
__.101(a))
    The proposed rule would mandate that all domestic sites in a 
cooperative study rely upon a single IRB for that study, regardless of 
the source of funding, unless otherwise required by law (e.g., FDA-
regulated device studies). Common Rule funding departments or agencies 
would also have the authority to determine that use of a single 
reviewing IRB is not appropriate for a particular study (so long as 
that decision is documented). This policy would apply regardless of 
whether the study underwent convened IRB review or expedited review. 
This proposal only affects the decision about which IRB would be 
designated as the reviewing IRB for compliance purposes. Related to 
this is a new provision at Sec.  __.103(e) requiring procedures that 
the institution and IRB would follow for documenting the institution's 
reliance on the IRB for oversight and the responsibilities of each 
entity. Also related to this, a new provision at Sec.  __.101(a) would 
give Common Rule departments and agencies the explicit authority to 
enforce compliance directly against IRBs that are not affiliated with 
an assured institution. In addition, the proposed rule would be 
modified to remove the current requirement at Sec.  __.103(d) that only 
with the approval of the department or agency head, an institution 
participating in a cooperative project may enter into a joint review 
arrangement, rely upon the review of another IRB, or make similar 
arrangements for avoiding duplication of effort.
    Currently, the choice to have cooperative research reviewed by a 
single IRB is voluntary under the Common Rule. In practice, most 
institutions have been reluctant to replace review by their local IRBs 
with review by a single IRB in part because of OHRP's current practice 
of enforcing compliance with the Common Rule through the institutions 
that were engaged in human subjects research, even in circumstances 
when the regulatory violation is directly related to the 
responsibilities of an external IRB. Review by multiple IRBs for 
cooperative research can add bureaucratic complexity to the review 
process and delay initiation of research projects without evidence that 
multiple reviews provide additional protections to subjects. Thus, the 
proposed changes at Sec.  __.101(a) are included in this NPRM to 
address this concern in anticipation of greater reliance on external 
IRBs in cooperative research, and to promote less bureaucratic 
complexity in the review process in multi-site studies.
    Ultimately, these revisions are expected to lower costs associated 
with multiple reviews for investigators, institutions, and IRBs. There 
may be some cost shifting as certain IRBs take on the role of reviewing 
IRB; however, these will be offset by savings at other IRBs no longer 
required to conduct additional reviews of the same research study. 
Initially, IRBs and institutions will have to draft and revise their 
policies regarding their reliance on single IRBs. It is expected that 
over time standardization in agreements will be achieved, and that 
reliance on single IRBs will be accepted because of their assured 
inclusion in oversight, which will result in reduced costs associated 
with multiple reviews and time savings for investigators who no longer 
must wait for multiple reviews to occur, with subsequent revisions and 
amendments. Likely, the hours spent here will replace hours spent 
reviewing and processing a submission that otherwise would be approved 
by the institution's IRB.
    The OHRP database of registered institutions and IRBs shows that 
there are 8,035 institutions with an FWA. The RIA estimates that these 
institutions would develop an average of 10 written joint review 
agreements with other institutions in 2019 prior to the first year of 
compliance. The RIA further estimates that each agreement would require 
an average of 10 hours of institution legal staff time and 5 hours of 
IRB administrator time to complete. The dollar value of their time is 
calculated by multiplying hours by their estimated 2016 and 2019 wages 
and adjusting for overhead and benefits.
    It is estimated that there are 202,617 annual reviews of multi-site 
protocols, and an average of 5 reviews per multi-site protocol, 
implying that there are 40,523 multi-site protocols reviewed each year. 
Of these protocols, an estimated 36,471 protocols (90 percent) do not 
involve medical devices; as a result, 4 of every 5 reviews would be 
eliminated. Accordingly, the RIA estimates that 145,884 annual reviews 
of protocols would no longer be conducted as a result of these proposed 
changes. Of these reviews, 48,317 would have undergone convened initial 
review, 21,708 would have undergone expedited initial review, 52,343 
would have undergone convened continuing review, and 23,517 would have 
undergone expedited continuing review based on the distribution of 
reviews presented in Table 3.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews and based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2019-2025 wages and adjusting for 
overhead and benefits.
    Present value benefits of $1,103 million and annualized benefits of 
$129 million are estimated using a 3 percent discount rate, and present 
value benefits of $849 million and annualized benefits of $121 million 
are estimated using a 7 percent discount rate. Present value costs of 
$155 million and annualized costs of $18.1 million are estimated using 
a 3 percent discount rate; present value costs of $138 million and

[[Page 54018]]

annualized costs of $19.7 million are estimated using a 7 percent 
discount rate. Table 22 summarizes the quantified and non-quantified 
benefits and costs of cooperative research.

     Table 22--Summary of Estimated Benefits and Costs of Cooperative Research (NPRM at Sec.  Sec.   __.114,
                                            __.103(e), and __.101(a))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    Reduction in number of reviews......            1,103               849               129               121
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Standardization of human subjects protections when variation among review IRBs is not warranted.............
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Time requirement to develop model                 155               138              18.1              19.7
     reliance agreement and written
     joint review agreements............
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

    t. Changes in the Elements of Consent, Including Documentation 
(NPRM at Sec. Sec.  __.116(a)(9), (b)(7)-(9), and __.117(b) in the 
NPRM)
    A new element of consent at Sec.  __.116(a)(9) applies to 
identifiable private information collected as part of a research 
activity. When identifiable private information is collected for 
research purposes, subjects must be provided with a statement 
describing the extent to which a subject's information will be made 
non-identified and used in future activities. An investigator must 
include in a consent form one of two statements:
     A statement that all identifiable information might be 
removed from the data and the data that is not identifiable could be 
used for future research studies or distributed to another investigator 
for future research studies without additional informed consent from 
the subject, if this might be a possibility; or
     A statement that the subject's data collected as part of 
the research, from which identifiable information is removed, will not 
be used or distributed for future research studies.
    The addition of the requirement to notify subjects of how their 
non-identified information might be used is viewed as a measure of 
respect for subjects, by informing them of possible uses of their 
information. Potential subjects can always decline to participate in 
the initial research if they are not willing to consent to the 
statement provided. This measure addresses concerns about people not 
being fully informed that their non-identified information could be 
used for research without their consent. These changes are expected to 
improve informed consent forms and processes, and ideally result in 
more informed decisions by prospective research subjects about whether 
to participate in research. The intent is to create greater 
transparency and improve the informed consent process. This addition 
would have to meet the documentation requirements at Sec.  __.117(b).
    While this new provision would require investigators to inform 
prospective subjects of how their non-identified information originally 
collected for research purposes might be used in future research 
studies, it is not expected that this change to have a measurable 
effect on the administrative costs to the research system. Under the 
current regulations, a majority of investigators do not restrict the 
future research use of non-identifiable information. Therefore, it is 
expected that in implementing this new notification requirement, the 
vast majority of investigators would elect option (1). In addition, 
under the current regulations, investigators may voluntarily restrict 
the future research use of non-identifiable information, such as in 
certain research involving vulnerable populations or a rare disease. We 
do not expect the new notification requirement to result in an increase 
in the number of investigators who would include option (2) in their 
consent forms and processes. When investigators choose to restrict the 
future research use of non-identifiable information under the current 
Rules, statements about such restricted future use are generally 
already included in the consent forms and processes. Therefore, for 
such research, the notification requirement is not expected to result 
in any change in practice.
    Since this notification requirement is not expected to change 
investigators' secondary use of non-identifiable information originally 
collected for research purposes, it is anticipated that investigators 
and institutions already have systems in place to track any 
restrictions investigators currently choose to implement. As likely is 
currently the case, it is anticipated that very few investigators would 
elect to offer the second option listed above because of the challenges 
of marking and tracking such decisions. Furthermore, since most 
investigators will likely elect the first option listed above, it would 
be reasonable for investigators and institutions to assume that the 
secondary research use of information would be permissible unless 
marked otherwise. Therefore, it would not be necessary to routinely 
track information obtained using the first option.
    Three additional elements of consent are proposed in Sec.  
__.116(b)(7)-(9). These three require that a subject be informed of the 
following, when relevant:
     That the subject's biospecimens may be used for commercial 
profit and whether the subject will or will not share in this 
commercial profit;
     Whether clinically relevant research results, including 
individual research results, will be disclosed to subjects, and if so, 
under what conditions; and

[[Page 54019]]

     An option for the subject or the representative to 
consent, or refuse to consent, to investigators re-contacting the 
subject to seek additional information or biospecimens or to discuss 
participation in another research study.
    These additional elements of consent are proposed to promote the 
goal of respect for persons and greater transparency in the research 
enterprise. Additionally, including the information referenced in these 
provisions in a consent form will help ensure that prospective subjects 
are given all information necessary for understanding why one might 
want to participate (or not) in a research study.
    The RIA estimates that there are 246,382 new protocols annually 
using identifiable information. For each protocol, it is estimated that 
investigators would spend an average of 15 minutes in 2016 updating 
consent forms to comply with the new requirements found in the NPRM at 
Sec.  __.116(a)(9) or (b)(7)-(9). Based on the estimates presented in 
Table 3, the dollar value of investigators' time is calculated by 
multiplying hours by their estimated 2016 wages and adjusting for 
overhead and benefits.
    The RIA assumes that no additional investigators would elect to 
offer the second option at Sec.  __.116(a)(9), and that the 
investigators who currently offer equivalent options already track the 
permissible and impermissible uses of information in line with the 
requirements discussed above. As a result, the RIA estimates that there 
are no additional costs associated with tracking. Public comment is 
requested on these assumptions.
    Present value costs of $4.55 million and annualized costs of $0.53 
million are estimated using a 3 percent discount rate; present value 
costs of $4.25 million and annualized costs of $0.60 million are 
estimated using a 7 percent discount rate. Table 23 summarizes the 
quantified and non-quantified benefits and costs of changes in the 
basic elements of consent, including documentation.

Table 23--Summary of Estimated Benefits and Costs of Changes in the Elements of Consent, Including Documentation
                          (NPRM at Sec.  Sec.   __.116(a)(9), (b)(7)-(9) and __.117(b))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Improved informed consent forms and processes...............................................................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Time to update consent forms........             4.55              4.25              0.53              0.60
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

u. Obtaining Consent to Secondary Use of Biospecimens and Identifiable 
Private Information (NPRM at Sec. Sec.  __.116(c)(1), (d)(1), (d)(4) 
and __.117(c)(3))
    The NPRM proposes to allow the use of broad consent to secondary 
research use of biospecimens or identifiable private information for 
unspecified research purposes. Such broad consent would have specified 
elements and limitations, and could be collected in both the research 
and non-research setting.
    Given the creation of the exemption for the maintenance and storage 
of biospecimens and identifiable private information for future, 
unspecified secondary research activities found in the NPRM at Sec.  
__.104(f)(1), it is envisioned that institutions creating these 
research repositories would need to develop tracking systems to monitor 
which biospecimens or what information may be used in secondary 
research by investigators. The Secretary of HHS would publish in the 
Federal Register one or more templates for broad consent (NPRM at Sec.  
__.116(d)(1)) that would contain all of the required elements of 
consent for broad, secondary use consent (NPRM at Sec.  __.116(c)). If 
investigators or institutions use the consent template without any 
changes and seek to use the exemption at Sec.  __.104(f)(2), IRB review 
is not required for these secondary studies, unless IRB review is 
required by law (e.g., FDA-regulated device studies).
    Seeking and obtaining consent to secondary research use of 
biospecimens and identifiable information is an additional flexibility 
proposed in the NPRM. However, it is not required. If broad consent has 
not been sought for the future research use of biospecimens or 
identifiable private information, then an investigator would need to 
have his or her project reviewed by an IRB and seek either study-
specific consent or a waiver of informed consent under the Common Rule. 
As discussed in section II.B of this preamble, the NPRM proposes 
stricter waiver criteria (NPRM at Sec.  __.116(e)(2) and (f)(2)) for 
biospecimens than for identifiable private information; these strict 
waiver criteria would apply regardless of whether the biospecimens are 
readily identifiable to the investigator. These waiver criteria would 
in effect make secondary research using a biospecimen largely 
impossible in the absence of obtaining subjects' broad consent for 
future use of their biospecimens. Because investigators would be 
required to use the Secretary's template for obtaining broad consent in 
order to be eligible for the new exemptions proposed in Sec.  
__.104(f), it is expected that minimal time would be spent updating 
consent forms or drafting wholly new consent forms. OHRP would develop 
one or more Secretary's templates for obtaining broad consent to 
secondary use of biospecimens or identifiable private information for 
subsequent use by investigators and institutions. OHRP staff time 
associated with developing this resource is

[[Page 54020]]

accounted for in section III.D.2.a of this RIA.
    As discussed earlier in this RIA (section III.D.2.n) it is 
anticipated that 6,428 FWA holding institutions (80 percent) would 
store and maintain clinical and non-clinical biospecimens and 
identifiable private information for unspecified future research 
studies in the manner prescribed under the new proposed exemption at 
Sec.  __.104(f)(1).
    As also discussed previously, extrapolations from 1999 data \91\ 
suggest that biospecimens are collected from as many as 30 million 
individuals and are stored each year for both clinical and research 
purposes. Approximately 9 million individuals' biospecimens (30 
percent) are collected for research purposes, and thus consent would be 
sought in the research context for the secondary use of these 
biospecimens. For these 9 million individuals per year, an investigator 
would spend an estimated five minutes per person conducting the consent 
process specific to seeking broad consent, and the subjects would spend 
an estimated five minutes engaging in the process of having their broad 
consent for future research uses of their biospecimens or information 
sought. This estimate of the investigator's time also includes the time 
for the investigator to log the information into the appropriate 
database. The RIA further estimates that investigators would spend 10 
minutes of time per protocol updating their study-specific consent form 
to include the language from the Secretary's consent template.
---------------------------------------------------------------------------

    \91\ Eiseman, E., Haga, S. (1999). Handbook of Human Tissue 
Sources: A National Resource of Human Tissue Samples. Washington, 
DC: RAND Corporation.
---------------------------------------------------------------------------

    In the clinical setting, approximately 21 million individuals' 
biospecimens (70 percent of the estimated 30 million individuals' 
biospecimens collected each year) are collected for clinical purposes. 
In the first year that the rule is implemented, as many as 21 million 
broad, secondary use consent forms could be collected from individuals. 
The RIA anticipates 10 minutes of a subject's time to engage in the 
consent process. The RIA further anticipates 10 minutes of an 
institutional employee's time at the IRB Administrative Staff level to 
seek consent and put the information in the appropriate tracking 
system.
    The NPRM proposes in Sec.  __.116(c)(1)(ii)(B) that once an 
individual gives broad consent to use his or her biospecimens in 
future, unspecified research studies, that consent may cover any 
biospecimen collected over the course of a 10 year period. Note that an 
institution may retain and use the biospecimens collected indefinitely. 
This provision is merely stating that every 10 years an institution 
must ask people whether or not they may use newly collected 
biospecimens in research. Given that an institution must seek broad 
consent from an individual only once over the course of a 10 year 
period, it is assumed that after the first year the rule is 
implemented, the number of individuals from whom an institution seeks 
broad consent will decrease.
    To account for this, the RIA assumes that after the first year that 
the rule is implemented, a fraction of the clinical subjects from whom 
secondary use consent is sought in year one would be sought in 
subsequent years. It is anticipated that in year two, secondary use 
consent would be sought in the clinical context from 10.5 million 
subjects (50 percent of the number of individuals involved in the year 
one estimates). It is anticipated that in year three and after, 
secondary use consent would be sought in the clinical context from 
approximately 6.3 million subjects each year (30 percent of the number 
of individuals involved in the year one estimates). As in year one, the 
RIA assumes that a prospective subject would spend 10 minutes of time 
undergoing the consent process and that an institutional employee at 
the IRB Administrative Staff level would spend 10 minutes of time 
conducting the consent process with an individual and updating the 
appropriate tracking system.
    Note that assumptions are not made about the extent to which 
institutions will use the tracked broad consent for the use of 
identifiable private information. While all institutions that conduct 
research with biospecimens will essentially need to create a research 
repository to continue that type of work under the NPRM proposals, such 
is not the case with identifiable private information. Identifiable 
private information is covered under the NPRM as it is under the 
current Rule. To that end, a research repository containing 
identifiable private information is not necessary to the research 
enterprise. Thus, the RIA notes that institutions likely will elect to 
store identifiable private information in these repositories, but it is 
unknown the extent to which institutions will elect to do this and the 
volume of identifiable private information that might be stored. 
Therefore, estimates are not provided specifically about the potential 
costs of obtaining broad consent and tracking the consent for future 
use of identifiable private information.
    The costs of the tracking system associated with an institution-
wide secondary use research repository are the design, implementation, 
and operation of the informatics system that would be required to 
document and keep up with thousands of consent documents per year. In 
addition, the institution would have to come up with some system to 
``mark'' or otherwise note which biospecimens and pieces of 
identifiable private information had been consented for use, and which 
ones had not, to make sure an individual's wishes regarding future use 
of his or her biospecimens and identifiable private information are 
carried out. It is estimated that these requirements would impose 
additional costs to develop or modify existing tracking systems at 80 
percent of 8,035 institutions with FWAs. It is estimated that these 
requirements would require 1.0 database administrator FTEs on average 
at these institutions. Based on the estimates presented in Table 3, we 
calculate the dollar value of their time by multiplying hours by their 
estimated 2016-2025 wages and adjusting for overhead and benefits. 
Public comment is requested on these estimates.
    Present value costs of $12,245 million and annualized costs of 
$1,435 million are estimated using a 3 percent discount rate; present 
value costs of $8,697 million and annualized costs of $1,238 million 
are estimated using a 7 percent discount rate. Table 24 summarizes the 
quantified and non-quantified benefits and costs of obtaining consent 
to secondary use of biospecimens and identifiable private information.

[[Page 54021]]



   Table 24--Summary of Estimated Benefits and Costs of Obtaining Consent to Secondary Use of Biospecimens and
      Identifiable Private Information (NPRM at Sec.  Sec.   __.116(c)(1), (d)(1), (d)(4) and __.117(c)(3))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Improved informed consent forms and processes, and reduction in time that would have been spent seeking and
     obtaining consent for secondary research use; retaining identifiers in research; better ensuring of the
     availability of biospecimens for future research activities................................................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Time to update consent forms,                  12,245             8,697             1,435             1,238
     document, and submit permissible
     and impermissible secondary uses of
     data; develop and maintain tracking
     system.............................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

v. Elimination of Requirement To Waive Consent in Certain Subject 
Recruitment Activities (NPRM at Sec.  __.116(g))
    The proposed rule would allow an IRB to approve a research proposal 
in which investigators obtain identifiable private information without 
individuals' informed consent for the purpose of screening, recruiting, 
or determining the eligibility of prospective human subjects of 
research, through oral or written communication or by accessing 
records, if the research proposal includes appropriate provisions to 
protect the privacy of those individuals and to maintain the 
confidentiality of the identifiable private information.
    This addresses concerns that the current regulations require an IRB 
to determine that informed consent can be waived under the current 
Sec.  __.116(d) before investigators may record identifiable private 
information for the purpose of screening, recruiting, or determining 
the eligibility of prospective subjects for a research study, provided 
that the research proposal includes an assurance that the investigator 
would meet the requirements for protecting the information as described 
in proposed Sec.  __.105. The current requirement is viewed as 
burdensome and unnecessary to protect subjects, and is inconsistent 
with FDA's regulations, which do not require a waiver of consent for 
such recruitment activities.
    This should result in some time and cost savings for both 
investigators and IRBs, but it would likely be small. The savings would 
come from IRBs no longer needing to consider whether informed consent 
can be waived for such preparatory-to-research activities. Savings 
would accrue for investigators who can proceed with such activities in 
less time.
    The RIA estimates that 1,621 annual initial reviews of protocols 
(0.5 percent) involve a waiver of consent for recruitment activities 
that would not be required as a result of these proposed changes. Of 
these reviews, 1,118 would have undergone convened initial review and 
502 would have undergone expedited initial review based on the 
distribution of reviews presented in Table 3. It is estimated that 
investigators spend an average of 15 minutes requesting a waiver of 
consent for recruitment activities when they submit a protocol for 
initial review. It is further estimated that IRBs typically use two 
primary reviewers for convened review and one primary reviewer for 
expedited review, and that primary reviewers spend an average of 15 
minutes determining whether informed consent can be waived. Based on 
the estimates in Table 3, the dollar value of their time is calculated 
by multiplying hours by their estimated 2016-2025 wages and adjusting 
for overhead and benefits.
    Present value benefits of $1.21 million and annualized benefits of 
$0.14 million are estimated using a 3 percent discount rate, and 
present value benefits of $0.85 million and annualized benefits of 
$0.12 million are estimated using a 7 percent discount rate. Table 25 
summarizes the quantified and non-quantified benefits and costs of 
eliminating the requirement to waive consent in certain subject 
recruitment activities.

   Table 25--Summary of Estimated Benefits and Costs of Elimination of Requirement To Waive Consent in Certain
                            Subject Recruitment Activities (NPRM at Sec.   __.116(g))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    Decreased time associated with                   1.21              0.85              0.14              0.12
     review.............................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

[[Page 54022]]

 
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

w. Requirement for Posting of Consent Forms for Common Rule Agency-
Supported Clinical Trials (NPRM at Sec.  __.116(h))
    A new provision would require that investigators or institutions 
post a copy of the final version of the consent form for each clinical 
trial conducted or supported by HHS on a publicly available federal Web 
site that would be established as an archive for such consent forms. 
The name of the clinical trial and information about whom to contact 
for additional information must be published with the consent form. The 
consent form must be published on the federal Web site within 60 days 
after the trial is closed to recruitment.
    It is recognized that certain information contained in an informed 
consent form is protected from disclosure under the Freedom of 
Information Act, the Trade Secrets Act, and/or FDA implementing 
regulations, and, therefore all informed consent forms for FDA-
regulated trials covered by this requirement would be subject to 
redaction before being posted.
    It is believed that public posting of consent forms would increase 
transparency, enhance confidence in the research enterprise, increase 
accountability, and inform the development of future consent forms, 
possibly resulting in future savings in time for investigators 
developing consent forms.
    It is expected that the Federal Web site would enable consent 
documents to be easily uploaded. Additional costs to the government 
would involve managing and maintaining the archive.
    According to queries of clinicaltrials.gov, there are an estimated 
5,270 clinical trials conducted or supported by Common Rule agencies, 
of which an estimated 575 are regulated by provisions in the Federal 
Food, Drug, and Cosmetic (FD&C) Act and Trade Secrets Act based on the 
information presented in Table 3. For the purpose of this analysis, it 
is assumed that each clinical trial is associated with one consent form 
that must be submitted to the HHS system by an investigator. The RIA 
estimates that investigators would spend an average of 15 minutes 
submitting each consent form. In addition, for the 575 clinical trials 
regulated by provisions in the FD&C Act and Trade Secrets Act, it is 
estimated that investigators would spend an average of 30 minutes 
redacting information before submission.
    In addition, submitted consent forms must be reviewed and made 
accessible to persons with disabilities in compliance with Section 508 
Amendment to the Rehabilitation Act of 1973. We estimate that each 
consent form contains an average of 10 pages and that 508-compliance 
costs an average of $30 per page. Based on the estimates presented in 
Table 3, the dollar value of their time is calculated by multiplying 
hours by their estimated 2016-2025 wages and adjusting for overhead and 
benefits.
    Present value costs of $14.6 million and annualized costs of $1.71 
million are estimated using a 3 percent discount rate; present value 
costs of $10.4 million and annualized costs of $1.49 million are 
estimated using a 7 percent discount rate. Table 26 summarizes the 
quantified and non-quantified benefits and the requirement for posting 
of consent forms for HHS-supported clinical trials.

  Table 26--Summary of Estimated Benefits and Costs of Requirement for Posting of Consent Forms for Common Rule
                           Agency-Supported Clinical Trials (NPRM at Sec.   __.116(h))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Increase transparency of HHS-supported clinical trials and inform the development of new consent forms......
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Development and management of                    14.6              10.4              1.71              1.49
     website, and preparation and
     submission of consent forms for
     posting............................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------


[[Page 54023]]

x. Alteration in Waiver for Documentation of Informed Consent in 
Certain Circumstances (NPRM at Sec.  __.117(c)(1)(iii))
    A new provision would be added allowing a waiver of the requirement 
to obtain a signed informed consent form if the subjects are members of 
a distinct cultural group or community for whom signing documents is 
not the norm. This would be allowed only if the research presents no 
more than minimal risk of harm to subjects and provided there is an 
appropriate alternative method for documenting that informed consent 
was obtained.
    Under the current Rule IRBs may waive the requirement for the 
investigator to obtain a signed consent form for some or all subjects. 
The current criteria for such a waiver may not be flexible enough for 
dealing with a variety of circumstances, such as when federally 
sponsored research that is conducted in an international setting where, 
for example, cultural or historical reasons suggest that signing 
documents may be viewed as offensive and problematic.
    This should not involve costs as its intent is to improve the 
informed consent process by providing more flexibility regarding the 
documentation of consent, an ethical gain, while reducing 
administrative requirements for investigators and research subjects in 
specific circumstances.
    Benefits and costs of this new provision are not quantified. Table 
27 summarizes the non-quantified benefits and costs of alteration in 
waiver for documentation of informed consent in certain circumstances.

 Table 27--Summary of Estimated Benefits and Costs of Alteration in Waiver for Documentation of Informed Consent
                           in Certain Circumstances (NPRM at Sec.   __.117(c)(1)(iii))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Improved informed consent process for distinct cultural groups and communities..............................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------

E. Sensitivity Analysis

    The total estimated costs of the proposed changes to the Common 
Rule are sensitive to assumptions regarding consent to secondary use of 
biospecimens and information. The RIA estimates that 60 percent of 
institutions with an assurance would implement a tracking system. Those 
institutions would require 1.0 FTEs on average to develop and maintain 
a tracking system. The sensitivity of estimated costs to these baseline 
assumptions is analyzed by calculating costs under alternative 
assumptions. That these institutions could instead require 0.75 FTEs or 
1.25 FTEs on average to develop and maintain a tracking system is 
considered. That 50 percent or 70 percent of assurance holding 
institutions could implement such a tracking system (rather than 60 
percent) is also considered. Table 28 reports present value costs using 
a 3 percent discount rate for these alternative and baseline 
assumptions.

 Table 28--Estimated Present Value Costs Using a 3 Percent Discount Rate (Millions of 2013 Dollars) of Costs of
   Obtaining Consent to Secondary Use of Biospecimens and Identifiable Private Information Using Baseline and
                                             Alternative Assumptions
----------------------------------------------------------------------------------------------------------------
                                                                    Percentage of institutions that implement a
                                                                                  tracking system
                FTEs required at each institution                -----------------------------------------------
                                                                    70 percent      80 percent      90 percent
----------------------------------------------------------------------------------------------------------------
0.75 FTEs.......................................................           8,700           9,666          10,633
1.00 FTEs.......................................................          10,956          12,245          13,534
1.25 FTEs.......................................................          13,212          14,823          16,435
----------------------------------------------------------------------------------------------------------------

F. Alternative Approaches to the Definition of Human Subject (NPRM at 
Sec.  __.102(e)) and Related Provisions

    Two alternative approaches for the treatment of biospecimens under 
the proposed rule were considered. These alternative proposals centered 
on concerns about potential identifiability of biospecimens and data 
derived from biospecimens.
Alternative Proposal A: Expand the Definition of ``Human Subject'' to 
Include Whole Genome Sequencing (WGS)
    Under Alternative Proposal A, the regulations at proposed Sec.  
__.102(e) would be amended to expand the

[[Page 54024]]

definition of human subjects to include more specifically whole genome 
sequencing data, or any part of the data generated as a consequence of 
whole genome sequencing, regardless of the individual identifiability 
of specimens used to generate such data. Investigators would not be 
allowed to remove identifiers from specimens or data to conduct whole 
genome sequencing without obtaining informed consent or a waiver of 
consent, because obtaining whole genome sequencing data about an 
individual would in and of itself cause the individual to meet the 
definition of a human subject. Written consent would generally be 
required for such activities.
    This requirement would not apply to specimens and information 
already collected at the time the final rule is published.
    Recent developments have made it possible to use whole genome 
sequencing information to re-identify non-identified data. Thus, even 
if such information is not ``individually identifiable'' (per the 
current Rule's standard of identifiability) it is appropriate to expand 
the definition of human subjects research in this way to afford 
individuals who are the subjects of such research the same protections 
as those given to the subjects of research using identifiable 
information or specimens. Therefore, it is anticipated that this change 
would increase protections for subjects of whole genome sequencing 
research. It would also increase the volume of studies for which 
investigators must seek and document informed consent, unless more 
stringent waiver criteria were met, and institutions will have to track 
the consent status of specimens and data. In addition, IRBs would have 
to review these studies unless the research meets the new proposed 
exemption in proposed Sec.  __.104(f)(2).
    It is estimated that there are 300 studies using whole genome 
sequencing data that are not subject to oversight by either the Common 
Rule or FDA regulations. This RIA estimates that under this 
alternative, 90 percent of these studies (270) would be eligible for 
the exemption proposed in Sec.  __.104(f)(2). For the remaining 30 
studies, it is anticipated that these would not be eligible for the 
exemption, and would require full IRB review. As required under Sec.  
__.104(c), an exemption determination would be made and documented for 
each of the 270 exemptible whole genome sequencing studies. It is 
anticipated that in 50 percent of these studies (135 studies), 
investigators will spend 30 minutes entering information into the HHS-
created decision tool in order for that tool to generate an exemption 
determination. In the remaining 135 studies, it is anticipated that 
investigators will spend 30 minutes preparing and submitting 
information about the study to an individual able to make exemption 
determinations (per Sec.  __.104(c)). An individual at the IRB voting 
member level will spend an estimated 30 minutes per study to make an 
exemption determination.
    In the absence of the proposed exempt category at Sec.  
__.104(f)(2), we estimate that in 2016 all 300 of these studies would 
undergo convened initial review. In subsequent years, an estimated 144 
protocols would undergo convened initial review, 108 would undergo 
convened continuing review, and 48 would undergo expedited continuing 
review, based on the distribution of reviews presented in Table 3.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    For Alternative Proposal A, present value costs of $0.57 million 
and annualized costs of $0.07 million are estimated using a 3 percent 
discount rate; and present value costs of $0.47 million and annualized 
costs of $0.07 million are estimated using a 7 percent discount rate. 
Table 29 summarizes the quantified and non-quantified benefits and 
costs of amending the definition of human subject.

 Table 29--Summary of Estimated Benefits and Costs of the Alternative Proposal A for Modifying the Definition of
                                    Human Subject (NPRM at Sec.   __.102(e))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Ensuring human subjects are protected in whole genome sequencing research not currently subject to
     oversight..................................................................................................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Increase in number of reviews.......             0.57              0.47              0.07              0.07
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    Time to obtain consent for activities involving whole genome sequencing.....................................
----------------------------------------------------------------------------------------------------------------

Alternative Proposal B: Classifying Certain Biospecimens Used in 
Certain Technologies as Meeting the Criteria for ``human subject''

    Under Alternative Proposal B, the regulations at proposed Sec.  
__.102(e) would be expanded to include biospecimens used in a 
technology capable of producing biologically unique information about a 
subject as well as the biologically unique information derived from a 
biospecimen. Only those technologies specifically listed on a newly 
created Secretary's List would be considered to have met this 
definition. For example, if whole genome sequencing was a technology 
included on the Secretary's List, then activities where a biospecimen 
(regardless of the investigator's ability to readily identify the 
person from whom the biospecimen was collected) was used in whole

[[Page 54025]]

genome sequencing research would be subject to the rules. Additionally, 
activities involving the information generated from a biospecimen used 
in a technology that appeared on this Secretary's List (regardless of 
the investigator's ability to readily identify a subject) would also 
fall under these regulations. Information derived from a technology 
appearing on the Secretary's List described above would be referred to 
as ``bio-unique'' information.
    This expansion would modestly increase the studies encompassed 
under the rule. This estimate is based on what is known about whole 
genomic research technologies that results in genome sequencing data 
(including DNA and RNA sequence data) that is unique to a single 
individual. It is estimated that there are 898 genomic research studies 
not currently subject to oversight that result in genome sequencing 
data unique to a single individual.
    One of the primary objectives of the NPRM has been to make the 
strength of protections commensurate with the level of risks of the 
research, and by doing so reduce unnecessary administrative burdens on 
research. That objective has been viewed as being particularly relevant 
to research involving only secondary use of biospecimens and data, 
which is relatively low-risk if appropriate protections of privacy and 
confidentiality are in place. Alternative Proposal B targets activities 
involving biospecimens where concerns about information risks indicate 
that additional regulatory oversight for these studies is appropriate.
    When the proposed exemption category at Sec.  __.104(f)(2) is 
considered, this RIA estimates that under Alternative Proposal B, 808 
studies (90 percent) would be eligible for exemption. For the remaining 
89 studies, it is anticipated that these would not satisfy the Sec.  
__.104(f)(2) requirements and would require full IRB review.
    As required under Sec.  __.104(c), an exemption determination would 
be made and documented for each of the 808 exemptible genomic research 
studies described above. It is anticipated that in 50 percent of these 
studies (404 studies), investigators will spend 30 minutes entering 
information into the HHS-created decision tool in order for that tool 
to generate an exemption determination. In the remaining 404 studies, 
it is anticipated that investigators will spend 30 minutes preparing 
and submitting information about the study to an individual able to 
make exemption determinations (per Sec.  __.104(c)). An individual at 
the IRB voting member level will spend an estimated 30 minutes per 
study to make an exemption determination.
    In the absence of the proposed exempt category of research at Sec.  
__.104(f)(1), the RIA estimates that as a result of the proposed 
expansion to the definition of human subject, all 898 of these studies 
would undergo convened initial review. In subsequent years, an 
estimated 431 protocols will undergo convened initial review, 322 will 
undergo convened continuing review, and 145 will undergo expedited 
continuing review based on the distribution of reviews presented in 
Table 3.
    The estimated costs to institution officials, IRB administrators, 
IRB administrative staff, IRB chairs, IRB voting members, and 
investigators of conducting these reviews are based on the estimates 
presented in Table 3. The dollar value of their time is calculated by 
multiplying hours by their estimated 2016-2025 wages and adjusting for 
overhead and benefits.
    For Alternative B, present value costs of $1.69 million and 
annualized costs of $0.20 million are estimated using a 3 percent 
discount rate; present value costs of $1.39 million and annualized 
costs of $0.20 million are estimated using a 7 percent discount rate. 
Table 30 summarizes the quantified and non-quantified benefits and 
costs of amending the definition of human subject.

 Table 30--Summary of Estimated Benefits and Costs of the Alternative Proposal B for Modifying the Definition of
                                    Human Subject (NPRM at Sec.   __.102(e))
----------------------------------------------------------------------------------------------------------------
                                             Present value of 10 years  by    Annualized value over 10 years  by
                                            discount rate (millions of 2013    discount rate  (millions of 2013
                Benefits                               dollars)                            dollars)
                                         -----------------------------------------------------------------------
                                              3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Benefits
    None................................  ................  ................  ................  ................
----------------------------------------------------------------------------------------------------------------
Non-quantified Benefits
    Ensuring that informational risks are minimized in research activities involving technologies capable of
     producing bio-unique information...........................................................................
----------------------------------------------------------------------------------------------------------------
                  Costs                       3 Percent         7 Percent         3 Percent         7 Percent
----------------------------------------------------------------------------------------------------------------
Quantified Costs
    Increase in number of reviews.......             1.69              1.39              0.20              0.20
----------------------------------------------------------------------------------------------------------------
Non-quantified Costs
    Time to obtain consent for activities involving the generation or use of bio-unique information.............
----------------------------------------------------------------------------------------------------------------

G. Regulatory Flexibility Analysis

    As discussed above, the RFA requires agencies that issue a 
regulation to analyze options for regulatory relief of small entities 
if a rule has a significant impact on a substantial number of small 
entities. HHS considers a rule to have a significant economic impact on 
a substantial number of small entities if at least 5 percent of small 
entities experience an impact of more than 3 percent of revenue.
    We calculate the costs of the proposed changes to the Common Rule 
to institutions with an FWA over 2016-2025 and then subtract the cost 
savings to these institutions over the same period. The estimated 
average annualized net cost to institutions with an FWA is $153,671 
using a 3 percent discount rate. The U.S. Small Business Administration 
establishes size standards that define a small entity. According to 
these standards, colleges, universities, and professional schools with 
revenues below $27.5 million and hospitals with revenues below $38.5 
million are considered small entities. It is not anticipated that a 
majority of

[[Page 54026]]

institutions with an FWA are in one of these categories.

IV. Environmental Impact

    We have determined under 21 CFR 25.30(k) that this action is of a 
type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

V. Paperwork Reduction Act

    This proposed rule contains collections of information that are 
subject to review and approval by the Office of Management and Budget 
(OMB) under the Paperwork Reduction Act (PRA), as amended (44 U.S.C. 
3501-3520). A description of these provisions is given in this document 
with an estimate of the annual reporting and recordkeeping burden.
    We invite comments on these topics: (1) The accuracy of the 
estimate of burden of the proposed collection of information; (2) ways 
to enhance the quality, utility, and clarity of the information to be 
collected; and, (3) ways to minimize the burden of the collection of 
information on respondents, including through the use of automated 
collection techniques, when appropriate, and other forms of information 
and technology.
    Title: Federal Policy for the Protection of Human Subjects.
    Description: In this document is a discussion of the regulatory 
provisions we believe are subject to the PRA and the probable 
information collection burden associated with these provisions. In 
general, the following actions trigger the PRA: (i) Reporting; (ii) 
Disclosure; (iii) Recordkeeping.
    Description of Respondents: The reporting and recordkeeping 
requirements in this document are imposed on Institutions, 
Institutional Review Boards, and Investigators involved in human 
subjects research conducted or supported or otherwise subject to 
regulation by any Federal department or agency that takes 
administrative action that makes the policy applicable to such 
research.

Sec.  __.101. To what does this policy apply (OMB Control No. 0990-
0260)

    Section __.101 is being amended to place unaffiliated Institutional 
Review Boards (IRBs) within the realm of entities to which the policy 
applies as described in Sec.  __.101(a) . This new provision gives 
Common Rule departments and agencies explicit authority to enforce 
compliance directly against IRBs that are not affiliated with an 
assured institution. This change should encourage institutions to more 
willingly rely on qualified unaffiliated IRBs for cooperative research, 
as is required under the proposed changes at Sec.  __.114. Burden 
estimates are included below in Sec.  __.114 summary.
    Section __.101 is also being amended to extend the regulations to 
cover clinical trials conducted at an institution in the United States 
that receives federal support from a Common Rule department or agency 
for non-exempt human subjects research, regardless of the funding 
source of the trial as described in Sec.  __101(a)(2). Extension of the 
regulations would not apply to clinical trials already regulated by 
FDA. We estimate that there are 1,399 clinical trials currently not 
subject to oversight by either the Common Rule or FDA regulations. We 
estimate that in 2016 all 1,399 of these clinical trials will undergo 
convened initial review. In subsequent years, we estimate that 672 
protocols will undergo convened initial review, 502 will undergo 
convened continuing review, and 225 will undergo expedited continuing 
review. We estimate the burden to institution officials, IRB 
administrators, IRB administrative staff, IRB chairs, IRB voting 
members, and investigators of conducting these reviews (24 hours per 
protocol) based on the estimates presented in Table 3 of section III of 
the preamble.

Sec.  __.103. Assuring Compliance With This Policy--Research Conducted 
or Supported by Any Federal Department or Agency (OMB Control No. 0990-
0260)

    Section __.103 is being amended, at Sec.  __.103(e), to require 
that for non-exempt research involving human subjects covered by this 
policy that takes place at an institution in which IRB oversight is 
conducted by an unaffiliated IRB that is not operated by the 
institution, the institution and the organization operating the IRB 
shall establish and follow procedures for documenting the institution's 
reliance on the IRB for oversight of the research and the 
responsibilities that each entity will undertake to ensure compliance 
with the requirements of this policy (e.g., in a written agreement 
between the institution and the IRB, or by implementation of an 
institution-wide policy directive providing the allocation of 
responsibilities between the institution and an IRB that is not 
affiliated with the institution). Burden estimates are included below 
in Sec.  __.114.

Sec.  __.104 Exempt Research (OMB Control No. 0990-0260)

    Section __.104 is being proposed, as described in Sec.  __.104(c), 
to require federal departments and agencies to develop a decision tool 
to assist in exemption determinations. Under the proposed rule, unless 
otherwise required by law, exemption determinations may be made by an 
individual who is knowledgeable about the exemption categories and who 
has access to sufficient information to make an informed and reasonable 
determination, or by the investigator or another individual at the 
institution who enters accurate information about the proposed research 
into the decision tool, which would provide a determination as to 
whether the study is exempt. If the tool is used, further assessment or 
evaluation of the exemption determination is not required. Burden 
estimates are included below in Sec.  __.115(a)(11).
    Section __.104 is being proposed, as described in Sec.  
__.104(d)(2), to require each federal department or agency conducting 
or supporting the research or demonstration projects exempted under 
Sec.  __.104(d), to establish on a publicly accessible federal Web site 
or in such other manner as the department or agency head may prescribe, 
a list of the research and demonstration projects that the federal 
department or agency conducts or supports under this provision. The 
research or demonstration project must be published on this list prior 
to or upon commencement of the research. We estimate that 4,377 exempt 
research and demonstration studies will be posted to the Web site 
annually, and that the information will be submitted to the Web site by 
individuals at the IRB administrative staff level, an estimate of 1.82 
person-hours per protocol (7966.14 burden hours).

Sec.  __.105 Protection of Biospecimens and Identifiable Private 
Information, (OMB Control No. 0990-0260)

    Section __.105 is being proposed, as detailed in Sec.  __.105(a), 
to require institutions and investigators conducting research subject 
to the Common Rule, or that is exempt under Sec. Sec.  __.104(e) or (f) 
to implement and maintain reasonable and appropriate safeguards to 
protect biospecimens, or identifiable private information they collect, 
store or use for research. The Secretary of HHS will establish and 
publish a list of specific measures that the institution or 
investigator may implement that will be deemed to satisfy the 
requirement for reasonable

[[Page 54027]]

and appropriate safeguards. The list will be evaluated as needed, but 
at least every 8 years, and amended, as appropriate, after consultation 
with other federal departments and agencies. Institutions and 
investigators may choose either to apply the safeguards identified by 
the Secretary as necessary to protect the security or integrity of and 
limit disclosure of biospecimens and electronic and non-electronic 
identifiable private information or to apply safeguards that meet the 
standards in 45 CFR 164.308, 164.310, 164.312, and 45 CFR 164.530(c). 
For federal departments and agencies that conduct research activities 
that is or will be maintained on information technology that is subject 
to and in compliance with section 208(b) of the E-Government Act of 
2002, 44 U.S.C. 3601 et seq., if all of the information collected, 
used, or generated as part of the activity will be maintained in 
systems of records subject to the Privacy Act of 1974, 5 U.S.C. 552a, 
and the research will involve a collection of information subject to 
the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq., these 
research activities automatically will be considered in compliance with 
the Secretary's reasonable and appropriate safeguards standards, unless 
or until any additional safeguards are identified by the Secretary of 
HHS.
    We estimate that 803 of the 8,035 institutions with FWAs (10 
percent) will be required to update their privacy and security 
standards to comply with the new requirements. At these institutions, 
we estimate that institutional officials and institutional legal staff 
will each spend 80 hours in 2016 and 20 hours in subsequent years to 
update and monitor their privacy and security standards. In addition, 
we estimate that 43,997 of 439,968 investigators (10 percent) will be 
required to adopt the updated privacy and security standards. We 
estimate that these investigators will each spend 40 hours in 2016 and 
10 hours in subsequent years to do so.

Sec.  __.111 Criteria for IRB Approval of Research, (OMB Control No. 
0990-0260)

    Section __.111 is being amended at Sec.  __.111(a)(8) to add a new 
requirement that if the investigator proposes a research plan for 
returning relevant results to subjects, then the IRB must determine 
that the plan is appropriate. We estimate that there are 324,187 
initial reviews of protocols annually. Of the 324,187 initial reviews, 
we estimate that 108,062 reviews (33 percent) will include a plan for 
returning results to subjects and that primary reviewers will spend an 
average of 15 minutes reviewing these plans.

Sec.  __.114 Cooperative Research (OMB Control No. 0990-0260)

    Section __.114 is being amended, as described in Sec.  __.114(b)(1) 
to require any institution located in the United States (U.S.) that is 
engaged in cooperative research to rely upon approval by a single IRB 
for that portion of the research conducted in the U.S. As described in 
Sec.  __.114(b)(2), cooperative research for which more than single IRB 
review is required by law (e.g., FDA-regulated device studies); or 
research for which the federal department or agency supporting or 
conducting the research determines and documents that the use of a 
single IRB is not appropriate for the particular study need not comply 
with this requirement. The OHRP database of registered institutions and 
IRBs shows that there are 8,035 institutions with an FWA. We estimate 
that these institutions will develop an average of 10 written joint 
review agreements with other institutions in 2018 prior to the first 
year of compliance. We estimate that each agreement will require an 
average of 10 hours of institution legal staff time and 5 hours of IRB 
administrator time to complete.

Sec.  __.115 IRB Records (OMB Control No. 0990-0260)

    Section __.115 is being amended, in Sec.  __.115(a)(8), to require 
the rationale for requiring continuing review for research that 
otherwise would not require continuing review as described in Sec.  
__.109(f)(1).
    We estimate that there are 108,873 expedited continuing reviews of 
protocols annually based on the distribution of reviews presented in 
Table 3 of the Regulatory Impact Analyses section of the preamble. Of 
these reviews, we estimate that 81,546 reviews (75 percent) will not be 
eliminated by other proposed changes to the Common Rule at Sec. Sec.  
__.101(b), __.104(d)(1)-(3), __.104(e)(1). We estimate that 40,773 of 
these 81,546 reviews (50 percent) will be discontinued and the 
remaining 40,773 reviews (50 percent) will continue and require 
documentation of the rationale for doing so. We estimate that IRB 
voting members will spend 1 hour per review providing documentation. In 
addition, we estimate that administrative staff at each IRB (total of 
3,499 IRBs) will spend 10 hours in 2016 updating their communication 
systems to no longer send continuing review reminders to certain 
investigators.
    Section __.115 is being amended at Sec.  __.115(a)(9) to require 
that the rationale for an expedited reviewer's determination that 
research appearing on the expedited list described in Sec.  
__.111(b)(1)(i) is more than minimal risk (i.e., an override of the 
presumption that studies on the Secretary's list are minimal risk).
    We estimate that there are 223,689 convened initial reviews and 
242,330 convened continuing reviews of protocols annually based on the 
distribution of reviews presented in Table 3 of the Regulatory Impact 
Analyses section of the preamble. Of these 223,689 convened initial 
reviews, we estimate that 2,237 reviews (1 percent) are eligible for 
expedited review because they are in a category of research that 
appears on the Secretary's list. Of these 2,237 reviews, we estimate 
that 1,118 reviews (50 percent) will undergo expedited review and the 
remaining 1,118 reviews (50 percent) will undergo convened review and 
require documentation of the rationale for doing so.
    Of the 242,330 convened continuing reviews, we estimate that 2,423 
reviews (1 percent) are eligible for expedited review because they are 
in a category of research that appears on the HHS Secretary's list. Of 
these 2,423 reviews, we estimate that 1,212 reviews (50 percent) will 
undergo convened review and will require documentation of the rationale 
for doing so. Due to the proposed elimination of continuing review of 
research under specific conditions (Sec. Sec.  __.109(f); __.115(a)(3), 
(8)), the remaining 1,212 reviews (50 percent) will not require review. 
Of these 1,212 reviews, we estimate that 606 reviews (50 percent) will 
not occur and the remaining 606 reviews (50 percent) will undergo 
expedited continuing review and require documentation of the rationale 
for doing so. We estimate that IRB voting members will spend 1 hour per 
review providing documentation when required.
    Section__.115 is being amended, at Sec.  __.115(a)(10) to require 
the written agreement between an institution and an external IRB 
specifying the responsibilities that each entity will undertake to 
ensure compliance with the requirements described in Sec.  __.103(e).
    Table 3 of section III of the preamble shows that there are 5,164 
FWA-holding institutions without an IRB and 2,871 FWA-holding 
institutions with an IRB. We assume that the 5,164 FWA-holding 
institutions without an IRB have an average of 1 IRB authorization 
agreement that would need to be

[[Page 54028]]

modified as a result of the new requirements for agreements between 
institutions and external IRBs in 2016. In addition, we assume that the 
2,871 FWA-holding institutions with an IRB have an average of 0.20 IRB 
authorization agreements that would need to be modified in 2016. We 
estimate that each agreement will require an average of 10 hours of 
institution legal staff time and 5 hours of IRB administrator time to 
complete.
    Section __.115, is being amended, in Sec.  __.115(a)(11), to 
require records relating to exemption determinations as described in 
Sec.  __.104(c). As part of this new requirement, OHRP will create an 
interactive exemption determination tool. We estimate that 6,754 annual 
reviews of protocols would no longer be conducted as a result of 
proposed changes under Sec.  __.104. As required under Sec.  __.104(c), 
an exemption determination must be made and documented for each of 
these 6,754 newly exempted studies. It is anticipated that in 50 
percent of these studies (3,377 studies), investigators will spend 30 
minutes entering information into the HHS-created decision tool in 
order for that tool to generate an exemption determination. In the 
remaining 3,377 studies, it is anticipated that investigators will 
spend 30 minutes preparing and submitting information about the study 
to an individual able to make exemption determinations (per Sec.  
__.104(c)). An individual at the IRB voting member level will spend an 
estimated 30 minutes per study to make an exemption determination.

Sec. Sec.  __.116 and __.117 General Requirements for Informed Consent 
(OMB Control No. 0990-0260)

    Section __.116 is being amended, as described in Sec.  
__.116(a)(9), to add a new basic element of consent that would apply to 
any research collection of identifiable private information. One of the 
following statements about such research collection much be provided to 
subjects: (i) A statement that identifiers might be removed from the 
data and the data that is not identifiable could be used for future 
research studies or distributed to another investigator for future 
research studies without additional informed consent from the subject 
or the representative, if this might be a possibility; or, (ii) a 
statement that the subject's data collected as part of the research, 
from which identifiers are removed, will not be used or distributed for 
future research studies. We estimate that there are 246,382 new 
protocols annually using individually identifiable information. For 
each protocol, we estimate that investigators will spend an average of 
15 minutes in 2016 updating consent forms to comply with the new 
requirements.
    Section __.116 is being amended, as described in Sec.  __.116(c) to 
allow broad consent to cover the storage, maintenance, and secondary 
research use of biospecimens and identifiable private information. 
Broad consent would be permissible for the storage or maintenance for 
secondary research of such information and biospecimens that were 
originally collected for either research studies other than the 
proposed research or non-research purposes. The broad consent document 
would also meet the consent requirement for the use of such stored 
biospecimens and information for individual research studies.
    We anticipate 6,428 FWA holding institutions (80 percent) will 
develop an institution-wide research repository of biospecimens and 
identifiable private information available for future research in the 
manner prescribed under the new proposed exemption at Sec.  
__.104(f)(1). We estimate that 80 percent of institutions with an FWA 
(6,428 institutions) will implement a tracking system. Those 
institutions will require 1.0 FTEs on average to develop and maintain a 
tracking system.
    It is anticipated that many investigators will choose to seek such 
consent in order to save time and burden by avoiding the need to (1) 
seek and obtain consent to every specific future research use, (2) seek 
full IRB review for research that meets one of the exempt research 
categories, or (3) seek IRB review for a waiver of consent.
    Section__.116 is being amended, as described in Sec.  __.116(h), to 
require that a copy of the final version of the consent form for each 
clinical trial conducted or supported by a Federal department or agency 
component conducting the trial on a publicly available federal Web site 
that will be established as a repository for such consent forms. The 
informed consent form must be posted in such form and manner as the 
department or agency head may prescribe, which will include at a 
minimum posting, in addition to the informed consent form, the name of 
the clinical trial and information about whom to contact for additional 
details about the clinical trial. The consent form must be published on 
the federal Web site within 60 days after the trial is closed to 
recruitment.
    We estimate that Common Rule departments and agencies supports 
5,270 new clinical trials annually, of which 575 are regulated by 
provisions in the FD&C Act and Trade Secrets Act based on the 
information presented in Table 3 of the Regulatory Impact Analyses 
section of the preamble. For the purpose of this analysis, we assume 
that each clinical trial is associated with one consent form that must 
be submitted by an investigator. We estimate that investigators will 
spend an average of 15 minutes submitting each consent form. In 
addition, for the 575 clinical trials regulated by provisions in the 
FD&C Act and Trade Secrets Act, we estimate that investigators will 
spend an average of 30 minutes redacting information before submission.

BILLING CODE 4150-36-P

[[Page 54029]]

[GRAPHIC] [TIFF OMITTED] TP08SE15.023


[[Page 54030]]


[GRAPHIC] [TIFF OMITTED] TP08SE15.024


[[Page 54031]]


[GRAPHIC] [TIFF OMITTED] TP08SE15.025


[[Page 54032]]


[GRAPHIC] [TIFF OMITTED] TP08SE15.026


[[Page 54033]]


[GRAPHIC] [TIFF OMITTED] TP08SE15.027

BILLING CODE 4150-36-C
    The total estimated burden imposed by these information collection 
requirements is 12,155,926 burden hours.
    It should be noted that the burden estimates for the Common Rule 
include those approved information requirements in: (1) OMB No. 0990-
0260, Protection of Human Subjects: Compliance with Federal Policy/IRB 
Recordkeeping/Informed Consent/Consent Documentation, approved through 
May 31, 2018; (2) OMB No. 0990-0263, Assurance Identification/IRB 
Certification/Declarations of Exemption Form (Common Rule), approved 
through March 31, 2018; (3) OMB No. 0990-0278, Federalwide Assurance 
(FWA) for the Protection of Human Subjects, approved through August 31, 
2017; and, (4) OMB No. 0990-0279, HHS, Registration of an Institutional 
Review Board ((IRB), approved through August 31, 2015. As such, they 
will be amended and submitted to OMB as revisions to currently approved 
collections once the rule is finalized and the collections are due for 
renewal.
    To ensure that comments on these new information collection 
requirements are received, OMB recommends that written comments be 
faxed to the Office of Information and Regulatory Affairs, OMB, Attn: 
[OS Desk Officer, FAX: 202-395-6974, or emailed to 
[email protected]. All comments should be identified with the 
title ``Federal Policy for the Protection of Human Subjects.''
    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C. 
3507(d)), the information collection provisions of this proposed rule 
will be submitted to OMB for review. These requirements will not be 
effective until OMB approves them.

VI. Summary of Comments Received on the 2011 Common Rule ANPRM

A. Initial Step Toward Modernization of the Common Rule: The Advance 
Notice of Proposed Rulemaking (ANPRM)

    In considering changes in the Common Rule, the ANPRM requested 
comment on possible changes to seven aspects of the current regulatory 
framework.
    1. Ensuring Risk-Based Protections
    2. Streamlining IRB Review of Cooperative Studies
    3. Improving Informed Consent
    4. Strengthening Data Protections To Minimize Information Risks
    5. Data Collection To Enhance System Oversight
    6. Extension of Federal Regulations
    7. Clarifying and Harmonizing Regulatory Requirements and Agency 
Guidance
    Public comments on the ANPRM initially were requested by September 
26, 2011; however, in response to public requests for an extension, the 
comment period was extended until October 26, 2011. A total of 1,051 
comments were received, with many commenters responding to all 74 
questions posed. Investigators comprised the largest group of 
commenters. Comments were also received from: Trade and professional 
associations; medical and social/behavioral research organizations; 
disease and patient advocacy groups; IRB members and staff; individual, 
private companies and the organizations representing them; and patients 
and research subjects. A large number of comments were lengthy and 
detailed, reflecting thoughtful consideration of the issues discussed. 
Many responses reflected the input of large research and health care 
organizations, including public university systems, research 
universities, academic medical centers, and medical schools, as well as 
networked health care providers. The greatest number of comments 
focused on the section addressing risk-based protections.
    In addition to reviewing the public responses to the ANPRM, in 
preparing the NPRM, the deliberations of the Presidential Commission 
for the Study of Bioethical Issues (the Commission) were taken into 
account. Consideration was also given to public comments received on 
the request for information issued by the Commission on March 2,

[[Page 54034]]

2011, that sought public comment on the current federal and 
international standards for protecting the health and well-being of 
participants in scientific studies supported by the federal 
government.\92\
---------------------------------------------------------------------------

    \92\ 76 FR 11482 (Mar. 2, 2011).
---------------------------------------------------------------------------

    These suggested revisions to the Common Rule may affect other 
regulatory protections, such as the other subparts of the HHS human 
subjects protection regulations in 45 CFR part 46 (Subparts B, C, and 
D, which deal with particular populations of vulnerable subjects, and 
Subpart E which addresses registration of IRBs), FDA regulations, and 
the HIPAA Privacy Rule (45 CFR parts 160 and 164, Subparts A and E). It 
is contemplated that other regulatory provisions implicated by the 
changes to the Common Rule may need to be harmonized, to the extent 
appropriate, with any final regulations modifying the Common Rule, 
through rule modification or guidance. Additionally, guidance and other 
information would also be revised and/or written to the extent 
necessary and appropriate.\93\
---------------------------------------------------------------------------

    \93\ Research not subject to the Common Rule may still be 
subject to FDA regulation or the HIPAA Privacy Rule.
---------------------------------------------------------------------------

B. ANPRM Issues and Public Comments Related To Improving Protections

1. Expanding the Scope of the Common Rule
    The ANPRM asked for public comments regarding two potential changes 
to the regulations at Sec.  __.101. The first would subject 
unaffiliated IRBs (IRBs that are not operated by an FWA-holding 
institution) that review research covered by the Common Rule to the 
requirements of the Common Rule. The second would extend the scope of 
research covered by the regulations.
    Holding Unaffiliated IRBs Directly Accountable for Compliance With 
Certain Regulatory Requirements: To address institutions' concerns 
about OHRP's practice of enforcing compliance with the Common Rule 
through the institutions that are engaged in human subjects research, 
the ANPRM asked for comments on making appropriate changes to the 
Common Rule enforcement procedures so external IRBs are held directly 
accountable for compliance with certain regulatory requirements.\94\
---------------------------------------------------------------------------

    \94\ See, e.g., the proposal on IRB accountability released by 
OHRP in 2009, at http://www.hhs.gov/ohrp/newsroom/rfc/com030509.html.
---------------------------------------------------------------------------

    Based on public comments received to a 2009 ANPRM \95\ on the issue 
of IRB accountability, the July 2011 Common Rule ANPRM considered 
adding a new provision that would give Common Rule departments and 
agencies the authority to enforce compliance directly against IRBs that 
are not affiliated with an institution that has an assurance registered 
with HHS. This provision would not extend the scope of research that is 
covered by the regulations; rather, it would expand the scope of those 
entities subject to compliance oversight.
---------------------------------------------------------------------------

    \95\ 74 FR 9578 (Mar. 5, 2009).
---------------------------------------------------------------------------

    Some public commenters responding to the 2011 ANPRM cautioned that 
extending compliance oversight to unaffiliated IRBs might serve as a 
disincentive for some IRBs to be the IRB of record for cooperative 
research. A majority of commenters expressed an opposing view; that is, 
holding external IRBs directly accountable for compliance with the 
regulations would increase the comfort level of institutions in 
accepting the regulatory review of an external IRB.
    Extension of Common Rule to Domestic Sites Funded by Common Rule 
Agencies: The ANPRM asked the public to consider a regulatory option to 
partially fulfill the goal of extending Common Rule protections to all 
human subjects research in the United States. The discussed policy 
would require domestic institutions that receive some federal funding 
from a Common Rule agency for nonexempt research with human subjects to 
extend the Common Rule protections to all human subjects research 
studies conducted at their institution.
    Although supporting the principle that all human subjects research 
regardless of funding source should be conducted ethically, public 
commenters generally expressed concern and caution about the ANPRM 
consideration for a variety of reasons. Behavioral and social science 
researchers thought that this approach would unnecessarily bring less-
than-minimal-risk research funded by non-federal sources (e.g., surveys 
or observational studies supported by the nonprofit sector) under 
burdensome regulatory requirements while not enhancing protections. 
Some commenters argued that the increased regulatory burden that would 
ensue was not warranted and would shift scarce oversight resources to 
review of research studies that are generally non-problematic and 
frequently supported by non-federal funds, such as some student or 
institutional research.
    Others argued that such a change was an overreach of federal 
oversight and constituted an unfunded mandate. Commenters from large 
academic research institutions felt that this change inappropriately 
focused heavily on academic institutions, which generally extend 
protections to all human subjects research at their institution, even 
if they have not ``checked the box'' \96\ on their FWA indicating that 
they do so. They argued that such a change would not reach those 
institutions already operating outside the federal research system and 
would limit flexibility in making risk-based determinations about the 
levels of review required.
---------------------------------------------------------------------------

    \96\ The FWA covers all nonexempt human subjects research at the 
submitting institution that is HHS-conducted or -supported, or 
funded by any other federal department or agency that has adopted 
the Common Rule and relies upon the FWA. It is not project specific. 
Domestic institutions may voluntarily extend their FWA (and thus a 
Common Rule department or agency's regulatory authority) to cover 
all human subjects research at the submitting institution regardless 
of the source of support for the particular research activity. See 
Office for Human Research Subject Protections. (2011, June 17). What 
research does the Federalwide Assurance (FWA) cover? Retrieved from 
Frequently Asked Questions: http://www.hhs.gov/ohrp/policy/faq/assurance-process/what-research-does-fwa-cover.html.
---------------------------------------------------------------------------

    Industry also expressed concern about having to comply with two 
sets of regulations, that is, FDA regulations at 21 CFR parts 50 and 56 
as well as the Common Rule. The ANPRM did not clarify that the changes 
under consideration would not require compliance with the Common Rule 
of non-federally funded research subject to regulation by FDA. However, 
there might continue to be research that would be subject to both sets 
of regulations involving federal funding of research concerning an FDA-
regulated product.
    Those commenters who supported a formal extension of the 
regulations cited the need to have one set of standards for all 
research, regardless of funding source; however, many noted that absent 
legislation covering all human subjects research conducted in the 
United States, it would be difficult to cover all research through a 
regulatory approach alone--gaps would still remain.
2. Safeguards for Information
    Definition of Private Information and Applying the HIPAA Standards 
of ``Identifiability'' to Research Governed by the Common Rule: The 
ANPRM suggested that the definition of ``identifiability'' in the 
Common Rule be modified to better harmonize it with other regulatory 
definitions of ``identifiability'' within HHS. The ANPRM considered 
adopting for purposes of the Common Rule the HIPAA Privacy Rule's 
standards of what constitutes individually identifiable information, a 
limited data set, and de-

[[Page 54035]]

identified information, in order to address inconsistencies regarding 
these definitions and concepts between the HIPAA Privacy Rule and the 
Common Rule. In addition, the ANPRM indicated that a prohibition on the 
re-identification of de-identified information (as defined in the HIPAA 
Privacy Rule) was being considered.
    Private information is not considered to be identifiable under the 
Common Rule if the identity of the subject is not or may not be 
``readily ascertained'' by the investigator from the information or 
associated with the information. In contrast, under the HIPAA Privacy 
Rule, health information is de-identified and thus exempt from the Rule 
only if it neither identifies nor provides a reasonable basis to 
believe that the information can be used to identify an individual. The 
HIPAA Privacy Rule provides two ways to de-identify information: (1) A 
formal determination by a qualified expert that the risk is very small 
that an individual could be identified; or (2) the removal of all 18 
specified identifiers of the individual and of the individual's 
relatives, household members, and employers, as long as the covered 
entity has no actual knowledge that the remaining information could be 
used to identify the individual (45 CFR 164.514(b)).
    The HIPAA Privacy Rule addresses some informational risks by 
imposing restrictions on how individually identifiable health 
information collected by health plans, health care clearinghouses, and 
most health care providers (``covered entities'') may be used and 
disclosed, including for research. In addition, the HIPAA Security Rule 
(45 CFR parts 160 and Subparts A and C of part 164) requires that these 
entities implement certain administrative, physical, and technical 
safeguards to protect this information, when in electronic form, from 
unauthorized use or disclosure. However, the HIPAA Rules apply only to 
covered entities (and in certain respects to their business 
associates), and not all investigators are part of a covered entity. 
Moreover, the HIPAA Rules do not apply specifically to biospecimens in 
and of themselves.
    A majority of the public commenters strongly opposed the ideas 
discussed in the ANPRM regarding the definition of ``identifiability''. 
Many indicated that the HIPAA Privacy Rule's more stringent standard of 
identifiability would expand what is considered identifiable for 
purposes of the Common Rule and thus greatly impede generally low-risk 
research without adding meaningful protections for human subjects. In 
particular, they asserted that the HIPAA standards were created to 
protect against disclosure of health information contained in medical 
records. As such, commenters argued, they are not appropriate for many 
types of research that would be covered by the Common Rule (e.g., 
behavioral and social science research). Others said this would be an 
extreme change in response to an as yet unidentified or clear problem. 
Commenters said that the information most at risk for inappropriate 
disclosure is the type of private health information that is already 
protected under the HIPAA Rules. Commenters feared that such a change 
in policy, while ``harmonizing'' the Common Rule certain HIPAA 
standards, would create inordinate burdens in terms of new 
documentation requirements and result in a requirement to apply the 
HIPAA standards to all types of research, regardless of the level of 
risk.
    Several commenters expressed concern about a prohibition against 
re-identifying de-identified private information (as defined by HIPAA), 
noting that sometimes it will be appropriate for investigators to re-
identify such information, for example, to return research results that 
have clinical relevance to the subjects. Also, some commenters noted 
that some research is specifically designed to test strategies for re-
identifying de-identified (as defined by HIPAA) information, so an 
absolute prohibition against re-identification would halt such 
research.
    Protecting Information: The ANPRM suggested establishment of 
mandatory data security and information protection standards for all 
studies that involve the collection, generation, storage, or use of 
identifiable or potentially identifiable information that might exist 
electronically or in paper form or contained in a biospecimen. It put 
forward the idea that these standards might be modeled after certain 
standards of HIPAA Rules and asked a series of questions about how best 
to protect private information.
    Some public comments reflected confusion about the focus of the 
suggested standards and whether they would apply to information or 
biospecimens that were not individually identifiable. Although most 
commenters confirmed the need to protect the privacy and 
confidentiality of information of human subjects in research, a 
majority expressed serious concerns about the merits of requiring all 
investigators to meet standards modeled on certain HIPAA standards, 
such as those in the HIPAA Security Rule. Most commenters expressed the 
opinion that certain HIPAA standards are not well suited to some 
research of various kinds carried out by investigators not subject to 
the HIPAA Rules. Some commenters claimed that the HIPAA privacy 
standards do not adequately protect individuals' information. Many 
commenters claimed that standards modeled after certain HIPAA standards 
would be unnecessarily burdensome for studies in the behavioral and 
social sciences where the data are often less sensitive than health 
information.
    Some comments maintained that HIPAA like standards would not always 
be suitable for the variety of research methods and procedures for the 
collection and storage of information in research activities not 
subject to the HIPAA Rules. Some commented that certain HIPAA standards 
would not be suitable because of the location of the research activity, 
or because the kind of institution supporting the research was 
significantly different from a covered entity. Others thought the HIPAA 
standards create confusion and complications for investigators and 
institutions that would increase if standards modeled on certain HIPAA 
standards were applied across the board. At the same time, regardless 
of the specific standards to be employed under this approach, several 
commenters noted that the additional administrative burden that might 
be created by establishing a data security and information protection 
system could be offset by the decreased time and attention IRBs would 
have to invest in reviewing every study that required data or 
biospecimen protections. They also noted that many institutions already 
have required data and biospecimen protection systems in place.
    Some commenters noted that expansion of some of the exemption 
categories could only be ethically acceptable if those research 
activities were subject to a requirement for data security and 
information protection, because information collected for some research 
studies would no longer be collected under a research plan approved by 
an IRB. With regard to an absolute prohibition against re-identifying 
de-identified data, many commenters expressed concern, and provided 
reasons why re-identification might be valid or even desirable, 
including the need to return clinically relevant research results to an 
individual. For example, if the research uncovers information that 
might have important clinical significance for an individual, re-
identification could be used so that the individual could get care. In 
addition, they pointed out that

[[Page 54036]]

the current Common Rule requires investigators that re-identify 
nonidentified private information as part of a research study to comply 
with the current Common Rule regulatory requirements.
3. Improving Informed Consent, Including Requiring Informed Consent for 
Research Use of Biospecimens and the Use of Broad Consent for Secondary 
Research Use of Biospecimens and Information
    The public was asked to comment on: The length and complexity of 
informed consent forms; additional information, if any, that should be 
required by the regulations to assure that consent forms appropriately 
inform subjects about alternatives to participation, as well as whether 
or not there should be modifications or deletions to the required 
elements; whether subject comprehension should be assessed, and if so, 
under what circumstances; whether changes to the Common Rule would 
necessitate conforming changes to the authorization requirements of the 
HIPAA privacy requirements; and whether additional requirements in the 
consent process are warranted, such as financial disclosures by 
investigators. The ANPRM also requested comment on the need for 
regulation of consent for the following: Research use of biospecimens 
collected for clinical purposes, consent for research use of pre-
existing data, and consent to secondary research use of data and 
biospecimens.
    Consent for Research Use of Biospecimens and Information Generally: 
The ANPRM also requested comment on the value of generally requiring 
written consent for research use of any biospecimens collected for 
clinical purposes after the effective date of the new rules (such as 
research with excess pathology biospecimens). Such consent could be 
obtained by use of a brief standard consent form agreeing to generally 
permit future research. This brief consent could be broad enough to 
cover all biospecimens to be collected related to a particular set of 
encounters with an institution (e.g., hospitalization) or even to any 
biospecimens to be collected at any time by that institution. The 
general rule as discussed in the ANPRM would be that a person needs to 
give consent, in writing, for research use of their biospecimens, 
though that consent need not be study-specific, and could cover open-
ended future research.
    The ideas presented in the ANPRM would be a substantial change from 
the current Rules in several ways. First, the current Rules allow 
research without consent when a biospecimen is used for research under 
conditions where the researcher does not possess information that would 
allow them to identify the person whose biospecimen is being studied. 
Thus, biospecimens collected as part of a non-research protocol (e.g., 
clinical care) could be made nonidentified and used in research as long 
as the researcher cannot identify the source of the biospecimen. The 
ANPRM consideration would no longer allow that to occur, generally 
requiring researchers to obtain consent for research use of clinical 
biospecimens, even if nonidentified. A waiver of consent under limited 
circumstances was contemplated in the ANPRM, but no specific waiver 
criteria were discussed.
    A majority of the commenters opposed the ANPRM's suggested 
requirement to have consent for research use of all biospecimens, 
regardless of identifiability, on both administrative and ethical 
grounds. Administrative reasons for opposition to the suggested consent 
requirements included the prohibitive costs to collect, log, and track 
consent status of data and biospecimens, and the considerable 
administrative efforts that would be required to keep track of the 
consent status. Commenters opposed to the suggested consent 
requirements on ethical grounds cited increased privacy risks to 
subjects arising from the need to maintain links between the consent 
documents and the biospecimens or data in order to ensure that any 
restrictions on the research use of such resources were honored. They 
also expressed their belief that convincing evidence of harm caused by 
research use of nonidentified clinical biospecimens without consent is 
lacking, especially when considering the public health benefit of such 
use, and noting that they were not convinced that the principle of 
autonomy outweighs or trumps the principle of beneficence. Some patient 
advocacy organizations also expressed concerns about the consequences 
of requiring consent for the use of nonidentified biospecimens. Yet, 
most of the comments from individual members of the public strongly 
supported consent requirements for use of their biospecimens, 
regardless of identifiability, or data.
    Many commenters expressed the opinion that the existing regulatory 
framework is adequate and that current practices should be maintained, 
stressing that the research use of nonidentified data or biospecimens 
does not involve risk to the research participant. One commenter noted 
that ``In our extensive professional experience working with 
biospecimens on a daily basis, the current system has worked well and 
has greatly enriched the opportunity for discoveries that were unknown 
at the time of collection and when research does not require subject 
identification or involve patient risk.'' In contrast, some commenters 
supported the idea of requiring consent for research use of all 
biospecimens, with one commenter noting simply that ``research use of 
data initially collected for non-research purposes should always 
require informed consent.'' Commenters particularly noted concerns 
about imposing consent requirements on the use of biospecimens already 
collected--that is, not grandfathering in such resources--especially if 
these biospecimens are nonidentified. Requiring that consent be 
obtained for the use of these materials could result in their being 
rendered useless for research, which would represent a cost of its own 
in terms of lost opportunity. This concern was based on the practical 
limitations involved in obtaining consent for biospecimens that were 
de-identified in the past, given that it may not be possible to re-
contact the original source.
    The objections raised by the commenters about the possible adverse 
consequences of requiring consent for the use of nonidentified 
biospecimens--including, in particular, the proposition that such a 
change might significantly compromise an important and relatively low-
risk area of research--resulted in suggestions in the comments that 
this should be systematically assessed before suggesting any new rules. 
In fact, several commenters suggested that data be collected on the 
cost and feasibility of instituting such a requirement before revising 
the Common Rule.
    Consent Rules for Research Use of Pre-existing Data: The ANPRM 
asked for comments on revising the consent rules for research use of 
data previously collected for purposes other than the suggested 
research study. First, if the data were originally collected for non-
research purposes, then, as is currently the rule, written consent 
would only be required if the researcher obtains information that 
identifies the subjects. There would accordingly be no change in the 
current ability of researchers to conduct such research using de-
identified data or a limited data set, as such terms are used in the 
HIPAA Rules, without obtaining consent.
    Second, if the data were originally collected for research 
purposes, then consent would be required regardless of whether the 
investigator obtains identifiers. Note that this would be a

[[Page 54037]]

change with regard to the current interpretation of the Common Rule in 
the case where the researcher does not obtain any identifiers. That is, 
the allowable current practice of telling the subjects, during the 
initial research consent, that the information they are providing will 
be used for one purpose, and then after stripping identifiers, allowing 
it to be used for a new purpose to which the subjects never consented, 
would not be allowed.
    Consent to Secondary Research Use of Data and Biospecimens Through 
Broad Consent: The ANPRM suggested that consent for the use of 
biospecimens or data could be obtained using a standard, short form, in 
which the subject could be asked to provide broad consent, that is, 
consent for a variety of potential future uses of their biospecimens or 
data. The requirement for consent could be waived in certain 
circumstances. These changes would apply only to biospecimens and data 
collected after the effective date of a new final rule.
    Public comments revealed variable opinions on this issue. Several 
commenters indicated that there is no need for additional regulations, 
with one university stating that it ``strongly opposes more restrictive 
regulations about the use of these biospecimens and sees no need to 
change the current regulations, even or perhaps especially in the case 
of secondary data analysis.'' Other commenters opposed broad consent, 
stating that researchers and clinicians should obtain specific consent 
from individuals for each research project. This opposition was made on 
the ethical grounds that because individuals are not fully informed of 
specific research purposes for broad consent, they can never be truly 
informed about the use of their data. In contrast, other commenters 
expressed clear support for general consent for secondary research use 
of biospecimens and data collected during research to exempt the 
research from IRB review, noting that ``we support the suggestion in 
the ANPRM to encourage general consent for the secondary research use 
of biospecimens and data and where this is not obtained IRB review is 
required.'' Other commenters favored requiring IRB review over 
permitting the use of a broad consent to approve secondary research use 
of identifiable data or biospecimens. These commenters believed that 
IRB consideration of consent requirements for individual research 
studies was more protective of human subjects than the ANPRM 
suggestions to permit broad consent for future use.
    With regard to the burden of obtaining consent for the research use 
of de-identified biospecimens, this requirement could be less 
burdensome than anticipated due to the ANPRM's suggested allowance of 
broad consent. While the ANPRM suggested requiring consent for the use 
of biospecimens, it suggested allowing a one-time, broad consent for 
future uses to be obtained with a template form which, if used without 
changes, would not require IRB review, and could be obtained at the 
same time as the initial research or clinical consent. Some commenters, 
particularly patients and patient advocacy groups, expressed concern 
about the burden of re-consenting patients for broad consent after 
biospecimens were collected.
    Several commenters suggested that data be collected on the cost and 
feasibility of instituting such a requirement before revising the 
Common Rule.
    In most instances, the consent requirements described above would 
have been met at the time that the biospecimens or data were initially 
collected, when, under the ANPRM the subject would have signed a 
standard, brief general consent form allowing for secondary research. 
This brief consent could be broad enough to cover all data and 
biospecimens to be collected related to a particular set of encounters 
with an institution (e.g., hospitalization) or to any data or 
biospecimens to be collected at any time by the institution, even as 
part of a research protocol.
    The ANPRM suggested that this standardized broad consent form would 
permit the subject to say no to all future research. In addition, the 
ANPRM acknowledged that there are likely to be a handful of special 
categories of research with biospecimens that, given the unique 
concerns they might raise for a significant segment of the public, 
could be dealt with by check-off boxes allowing subjects to separately 
say agree or disagree to that particular type of research.
    Further, the ANPRM suggested that the current prohibition that 
participation in a research study (such as a clinical trial) could not 
be conditioned on agreeing to allow future open-ended research using a 
biospecimen would be maintained. With regard to the secondary research 
use of pre-existing data, on those occasions when oral consent was 
acceptable under the regulations for the initial data collection, the 
ANPRM envisioned that subjects would have typically provided their oral 
consent for future research at the time of the initial data collection; 
a written consent form would not have to be signed in that 
circumstance.
    The ANPRM suggested that these changes would only be applied 
prospectively, not retrospectively. In other words, they would only 
apply to biospecimens and data that are collected after the effective 
date of the new rules. It also noted that there would be rules that 
would allow for waiver of consent under specified circumstances, though 
those conditions would not necessarily be the same as those for other 
types of research.
    Improving Consent Forms and Modifying the Required Elements of 
Consent: Public comments were largely in favor of finding ways to 
improve consent forms. However, commenters cited several systemic 
concerns that could be obstacles to shortening and simplifying forms, 
such as regulatory, legal, and institutional requirements, and the 
complexity of some studies. Of those responding to questions about the 
causative factors, blame for making forms long and complex was shared 
by sponsors of clinical trials, IRBs, regulatory agencies, and 
institutional legal counsel. The types of information cited as 
contributing to the excessive lengths of forms included the requirement 
to describe all reasonably foreseeable research risks and the 
complexity of study procedures. There was no consensus on how to better 
explain alternatives to research participation and few comments were 
submitted on this topic.
    Commenters offered a few suggestions for modifying or deleting the 
required elements of consent, such as removing boilerplate language 
that only protects institutions and research sponsors, as well as 
removing some of the required elements for minimal risk research. 
However, many felt that guidance, rather than regulatory change, would 
better improve the development of consent forms. Although many 
commenters noted the need for shorter and more comprehensible consent 
forms, most felt that the required elements of consent articulated in 
the Common Rule are sufficient. Commenters overwhelmingly supported the 
goals articulated in the ANPRM, but cautioned against an overly 
prescriptive or rigid approach to consent forms. However, several 
commenters requested guidance on what might be included in a consent 
form for future research use of identifiable information and 
identifiable biospecimens to ensure that such forms satisfied the 
consent requirements of the Common Rule.
    A majority of commenters supported the development of regulations 
or guidance designed to encourage

[[Page 54038]]

assessment of the extent to which human subjects comprehend consent 
forms, at least for certain types of higher risk studies or certain 
types of subject populations. Others argued that the regulations at 
Sec.  __.116 already contain language implying the need to ensure 
comprehension through the use of the terms ``legally effective informed 
consent'' and ``language understandable to the subject.''
    Finally, many commenters supported making changes to HIPAA 
authorization requirements, as necessary to conform to provisions of 
the Common Rule. In addition, most commenters were supportive of 
requiring investigators to disclose in consent forms certain 
information about the financial relationships they have with study 
sponsors.
    Criteria for Waiver of Consent: The ANPRM asked whether changes to 
the regulations would clarify the current four criteria for waiver of 
informed consent and facilitate their consistent application. Few 
comments were received on this topic although many commenters expressed 
support for clarifying the key terms through guidance or altering the 
criteria. In particular, most comments on this topic noted the 
confusion that IRBs face when trying to understand the meaning of the 
terms ``practicable'' and ``adversely affect the rights and welfare of 
subjects.'' Some commenters expressed the opinion that the waiver 
criterion concerning rights and welfare should be interpreted to 
include reference to rights conferred by other federal laws or 
regulations, state or local laws, or laws in other countries where 
research is to be conducted. Some comments reflected concerns about 
privacy or security.
    The ANPRM also asked for comments on the information investigators 
should be required to provide to prospective subjects in circumstances 
where the regulations would permit oral consent. Additional questions 
focused on whether there are additional circumstances under which it 
should be permissible to waive the usual requirements for obtaining or 
documenting informed consent, and whether there are types of research 
in which oral consent without documentation should not be permitted. 
There were few responses to these questions and no common themes or 
consensus among those submitted. However, several commenters pointed to 
the need to consider community norms throughout the consent process, 
including its documentation.
4. Improving the Collection and Analysis of Adverse Event Reports
    The ANPRM asked the public to consider a number of changes to 
improve the current system for the real-time prompt collection of data 
regarding adverse events. The changes that the ANPRM stated were under 
consideration were intended to simplify and consolidate the reporting 
of information that is already required to be reported by an 
investigator, and not to expand the information that has to be 
reported. In addition to these changes, the ANPRM indicated that the 
Federal Government was also considering creating a central web-based 
repository to house a great deal of the information collected through 
the portal.
    Although a number of commenters applauded the goal of easing and 
harmonizing reporting requirements, most expressed concerns about 
collecting data on unanticipated problems and adverse events in a 
central database. Those who supported the concept of centralized 
reporting asked for more detail on what such a system would entail. 
More specifically, several commenters noted that IRBs sometimes 
struggle with what should be reported and with distinguishing between 
the Common Rule term ``unanticipated problems'' and the FDA term 
``adverse events.'' Commenters noted that under the Common Rule at 
Sec.  __.103(b)(5), each institution determines through its own 
policies the procedures for reporting unanticipated problems to 
department or agency heads. As a result, there is no standardized 
definition of ``unanticipated problems,'' so each institution may be 
reporting different events. Commenters also sought better guidance on 
those terms and encouraged agencies to clarify meanings and reporting 
requirements.
    Commenters stated that a standardized, streamlined set of data 
elements, a single web-based reporting tool that facilitates delivery 
to agencies and oversight bodies, and harmonized Federal agency 
guidance would simplify the process. However, many expressed skepticism 
that harmonization across Federal agencies could occur.
    With regard to a centralized database, many commenters expressed 
concerns regarding the value in terms of cost and time with compiling 
such data, gleaned from diverse studies and sources, in order to 
conduct an integrated analysis. They commented that it is unclear how 
the data would be useful beyond a specific study and unclear who would 
have access to the data and how it would be managed and interpreted to 
better inform the regulatory process. Commenters asked, if the data 
reporting is real-time, who is expected to develop such a system and 
review incoming data to coordinate the appropriate response? Many 
commenters questioned the validity of data collected in such a generic 
manner and the ability to draw generalizable conclusions based on data 
collected from varied sources and contexts. Several commenters said 
that before implementing such a central repository, a thorough cost-
benefit analysis should be conducted regarding strengths and 
limitations of similar data repositories. Until the utility of such a 
centralized system could be demonstrated, especially when compared to 
the current decentralized system, many felt the burden of creating such 
a system would not be counterbalanced by the benefit of added 
protections. Along these lines, commenters also questioned the utility 
of counting how many human subjects are enrolled in trials, stating 
that this would not be a meaningful way to develop risk estimates.
    Many commenters cited the adequacy of current reporting systems, 
despite the need for improvement. Centralized reporting of adverse 
events would represent a dramatic change from how events are collected 
and reported now. For example, sponsors of clinical trials are 
responsible for continuously monitoring their trials, adverse events 
must be reported to sponsors, and new reporting would not substitute 
for reports to sponsors. In addition, under FDA regulations, when 
applicable, safety information from non-U.S. clinical trials may need 
to be reported. Moreover, sponsors and funding agencies probably would 
not rely on extracting information from a federal database as the 
source of information to meet all of their safety oversight obligations 
and would likely still require investigators to complete adverse event 
case report forms as well as rely on the use of Data Safety Monitoring 
Boards. Commenters also raised concerns that the use of an electronic 
centralized reporting system could be a substantial burden on 
investigators, may potentially decrease investigators' willingness to 
participate in trials, and may encourage the conduct of studies outside 
the regulations. If reporting systems were now required to also gather 
and store unanticipated problems in addition to adverse events, 
commenters said the system would become unwieldy, run the risk of 
creating long lag times in analysis, and draw low risk events into a 
system that should be focused on the

[[Page 54039]]

highest risk studies. Several commenters recommended that more efforts 
be made to improve current reporting systems, particularly 
ClinicalTrials.gov.
    Based on the public comments, the NPRM does not pursue a 
centralized reporting system and thus this issue is not addressed 
further. OHRP will continue to engage in discussions with FDA and 
Common Rule departments and agencies regarding clarifying reporting 
terms and requirements.
5. Identifiability of Biospecimens
    The ANPRM suggested that, regardless of what information is 
removed, it is possible to extract DNA from a biospecimen itself and 
potentially link it to otherwise available data to identify 
individuals. In addition, irrespective of whether biospecimens are 
considered individually identifiable, the ANPRM sought comment on 
whether the regulations should be changed to respect individuals' 
interest in being able to decide whether their biospecimens would be 
available for research, even if the biospecimen was not associated with 
any identifiable information. Consequently, it asked for public comment 
on the value of categorizing all research involving the primary 
collection of biospecimens as well as storage and secondary analysis of 
existing biospecimens as research involving identifiable information.
    The ANPRM asked whether some types of genomic data should be 
considered identifiable and, if so, which types (e.g., genome-wide 
single nucleotide polymorphism [SNP] analyses or whole genome 
sequences). It also asked whether human biospecimens should be 
considered inherently identifiable. A majority of commenters opposed 
changing the Common Rule to consider all biospecimens identifiable as 
defined by the existing regulations at Sec.  __.102(f)(2) (and thereby 
categorizing their use as research involving a human subject), and 
expressed concern that doing so would significantly slow advances in 
research and human health. Several commenters noted that, although it 
is theoretically plausible to identify a person based on his or her 
biospecimen, the likelihood remains remote enough to argue against the 
presumption that the sources of all biospecimens are identifiable and 
cited a study showing that the risk of re-identification from a system 
intrusion of databases was only 0.22%.\97\ Other commenters cited the 
administrative burden that would be exacted should such an 
interpretation be implemented, without sufficient evidence that such an 
interpretation would be reasonable or enhance protections.
---------------------------------------------------------------------------

    \97\ Kwok P et al. Harder Than You Think: A Case Study of Re-
Identification Risk of HIPAA-Compliant Records. NORC at The 
University of Chicago and Office of the National Coordinator for 
Health Information Technology. 2011. http://www.amstat.org/meetings/jsm/2011/onlineprogram/AbstractDetails.cfm?abstractid=302255.
---------------------------------------------------------------------------

    Commenters were mostly concerned with the cost and burden that 
would be imposed by the requirement to obtain consent. Commenters 
anticipated these costs to include obtaining consent from participants 
and the administrative efforts required to keep track of the consent 
status of biospecimens. Most commenters did not provide detailed cost 
estimates with their comments; data are specifically requested in 
response to this NPRM. In addition, estimates of the type and number of 
studies that could not be pursued using existing samples and data 
because of the absence of sufficient consent are requested. Comment is 
also sought on the value to the public and research participants of 
being asked their permission for research use of their data and 
specimens.
    Several commenters also stated that if the Common Rule were 
modified such that all biospecimens were covered under the rule 
regardless of their identifiability, there still might be some 
activities involving biospecimens or types of biospecimens that should 
be considered exempt or ``excused.'' Suggestions included:
     Identifying markers for cancer prognosis or prediction of 
response to cancer therapy, or identifying cancer molecular targets 
(molecular research)
     Basic science research (including analysis of biological 
processes)
     Research of rare conditions and diseases
     Pediatric research
     Research with samples that lack potentially identifying 
information, such as serum or plasma not containing DNA
     Biospecimens lacking nucleic acids (such as certain red 
blood cells, expiratory gases)
     Blood culture bacteria
     Bacterial and viral specimens (this was listed in a 
comment as a public health issue)
     Protein analysis
     Statistical method development (to the extent that this 
development is related to biospecimens)
     New molecular methods to detect infectious agents
     Use of specimens to develop and validate new assays for 
infectious agents
     Archival paraffin blocks
    One commenter also suggested that the Rule could propose a 
definition for biospecimen such that the term does not include sample 
types that lack DNA.
    In addition, some commenters noted that the recommendation to 
require consent might privilege the Belmont Report's principle of 
autonomy over the principle of justice, because requiring consent could 
result in lower participation rates in research by minority groups and 
marginalized members of society. The literature on consent rates in 
studies involving biospecimens suggests that while minority consent 
rates in some cases may be lower than non-minorities, when asked to 
consent, minority consent rates are still higher than 
projected.98 99 100 Furthermore, better communication and 
community engagement with members of specific minority groups is needed 
to understand and address concerns related to research, and these 
measures could substantially improve participation rates. An increase 
in trust and partnership is likely to increase participation rates; 
using their samples and data without permission will hinder true 
partnership.
---------------------------------------------------------------------------

    \98\ Pentz RD et al. Research on Stored Biological Samples: 
Views of African American and White American Cancer Patients. 
American Journal of Medical Genetics, Part A. 2006 Apr 1; 
140(7):733-9.
    \99\ Chen DT et al. Research With Stored Biological Samples; 
What Do Research Participants Want? Archives of Internal Medicine. 
2005 Mar 28; 165(6):652-5.
    \100\ Scott et al. Biospecimen Repositories: Are Blood Donors 
Willing to Participate? Transfusion. 2010 September; 50(9): 1943-
1950.
---------------------------------------------------------------------------

C. ANPRM Issues and Public Comments Related To Reducing Regulatory 
Burden

1. Activities Excluded From the Policy
    The ANPRM asked questions about the definition of research and 
whether various activities should be excluded from the Common Rule, 
either by changing the definition of research or by adding exemptions, 
or both. The ANPRM sought comment on whether and, if so, how, the 
Common Rule should be changed to clarify whether quality improvement 
activities, program evaluation studies, or public health activities are 
covered. It also asked whether there are specific types of studies for 
which the existing rules are inappropriate. If so, comments were sought 
on whether this problem should be addressed through modifications to 
the exemption categories, or by changing the definition of ``research'' 
used in the Common Rule to exclude

[[Page 54040]]

some of these studies, or a combination of both.
    If the definition of research were to be changed, public comment 
was sought on how excluded activities should be defined (e.g., 
``quality improvement'' or ``program evaluation''). With regard to 
quality improvement activities, the public was asked to comment on 
whether it might be useful to adopt the distinction made by the HIPAA 
Privacy Rule, which distinguishes between ``health care operations'' 
and ``research'' activities, defining ``health care operations'' to 
include, among other activities, ``conducting quality assessment and 
improvement activities, including outcomes evaluation and development 
of clinical guidelines, provided that the obtaining of generalizable 
knowledge is not the primary purpose of any studies resulting from such 
activities.''
    A majority of public comments supported excluding the following 
from the regulatory requirements: quality improvement activities, 
public health activities, and program evaluation. Many of these 
commenters argued that the public benefits resulting from these 
activities justified their practice, particularly given the generally 
low risk involved. Some argued that for some legally mandated 
activities designed to accomplish a public good, it would be 
inappropriate for IRBs or individuals to be able to impede or thwart 
the execution of those mandated activities. A majority of comments also 
favored distinguishing between research and health care operations, as 
such terms are defined in the HIPAA Privacy Rule, and excluding the 
latter from the policy.
    Some commenters noted that people involved in these various 
activities are protected in other ways, and alluded to the sorts of 
measures that provide a measure of protection. Others suggested that 
any exclusions should be limited to data collection and analysis 
activities, or to activities below a certain threshold of risk (i.e., 
minimal risk). A minority of comments objected to these exclusions, 
arguing that these activities represent encroachments on their 
individual rights and privacy, and that oversight in accordance with 
the Common Rule requirements would be more protective.
    The overwhelming majority of public comments responding to the 
question about excluding specific fields of study from the regulatory 
requirements of the Common Rule supported explicitly excluding certain 
activities from the definition of research versus modifying the 
exemption categories. The overwhelming majority of these comments 
focused on oral history. Some of the comments were virtually identical 
and appear to have been coordinated. Many of the comments reflected the 
view that the Common Rule was not designed or intended to include oral 
history activities, and that the ethical codes pertaining to oral 
history procedures are not consistent with the application of ethical 
principles reflected in the Common Rule.
    A smaller number of similar comments were submitted with respect to 
various humanities disciplines and journalism. A significant minority 
of commenters opposed the exclusion of any fields of study, arguing 
that the activity itself rather than the academic discipline or 
training of the investigator should be the basis for the assessment of 
whether the activity should be excluded. Some of the commenters 
recommended that the definition of research be focused more explicitly 
by being limited to ``biomedical and behavioral research,'' in 
accordance with the statutory provision underlying the Common Rule. A 
significant number of commenters recommended that guidance should be 
issued to clarify how the definition of research should be applied, 
with cases and explanations.
2. Research Exempt From IRB Oversight
    Exemption Determination: The ANPRM discussed a mechanism to (1) 
register exempt research, and (2) audit a small but appropriate portion 
of such research, which would still be subject to other regulatory 
protections such as the suggested data security and information 
protection standards and certain consent requirements. The term 
``excused'' rather than ``exempt'' was recommended to describe these 
categories of research, because they are not entirely exempt from 
oversight.
    The ANPRM discussed a tracking mechanism to enable institutions to 
assure that such research meets the criteria for inclusion in the 
suggested ``excused'' categories. The original recommendations would 
require investigators to register their study with an institutional 
office by completing a brief form, thus eliminating the current 
practice of not allowing investigators to begin conducting such studies 
until a reviewer had determined it met the criteria for excused 
research. This would make the institution aware of key information 
about the research (such as the purpose of the research and the name of 
the study's principal investigator), without also requiring that the 
activity undergo a review that, if not done in a timely manner, could 
slow the research without adding any significant protection to 
subjects. In addition the institution could choose to review some of 
the submissions at the time they are filed and, if deemed appropriate, 
require that the study be sent for expedited review or, in rare cases, 
convened IRB review. It would be made clear that the regulations would 
not require, and in fact, would discourage, having each of these 
registration forms undergo a comprehensive administrative or IRB review 
prior to commencing the study or even afterward.
    The auditing requirement was intended to encourage institutions to 
use the regulatory flexibility suggested for the ``excused'' categories 
of research. The auditing requirement would have provided institutions 
with information needed to assess their compliance with the new 
``excused'' categories without unnecessarily subjecting all such 
research to either prospective review, or even routine review sometime 
after the study is begun. Note that currently, OHRP recommends that 
there be some type of review by someone other than the investigator to 
confirm that a study qualifies as exempt, and many institutions do 
impose such a requirement even though such a requirement is extra-
regulatory.\101\
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    \101\ Office for Human Research Protections. (2011, January 20). 
Exempt Research Determination FAQs. Retrieved from Frequently Asked 
Questions About Human Research: http://www.hhs.gov/ohrp/policy/faq/index.html.
---------------------------------------------------------------------------

    The ANPRM also asked whether this research should be called 
``excused'' or some other term, whether it was acceptable for 
investigators to independently determine whether their research was 
excused, whether review of all registrations should be required, and 
whether there should be a time limitation or waiting period before 
excused research could begin. The ANPRM also asked whether it was 
appropriate to require institutions holding an FWA to conduct 
retrospective audits of a percentage of the excused studies to make 
sure they qualify for inclusion in an excused category, and if so, how 
such audits should be conducted.
    Commenters overwhelmingly expressed concerns about adopting the 
term ``excused'' to describe this area of research and suggested the 
term ``registered'' should such a system be adopted. Commenters 
recommended the term ``registered'' because such studies would not be 
exempt or excused from other requirements, such as compliance with data 
and security provisions as well as, in certain circumstances, informed 
consent requirements. In general, commenters were not necessarily 
opposed to the concept of registration but sought further information 
on what this process would entail.

[[Page 54041]]

    Public commenters also expressed concerns about allowing an 
investigator to independently make the determination that his or her 
research is exempt. Other commenters suggested that this practice would 
be acceptable for some investigators, whose research is well known to 
IRB members, and is clearly within an exempt category. The ANPRM noted 
concerns that some exempt research was unnecessarily delayed by 
requirements of some institutions to review the research to make an 
exemption decision.
    Several institutions reported that they already as a matter of 
policy require investigators to submit exempt studies to the IRB, not 
necessarily for full board review, but to ensure that the exempt 
determination is valid. These decisions typically are made by the IRB 
administrator and never involve full review unless there is concern 
about the exemption status. Thus, they felt the registration 
requirement was unnecessary and would add new administrative burdens 
for research already considered low risk.
    Other commenters, such as investigators conducting research 
currently considered exempt, were strongly opposed to a registration 
requirement because it would add a new burden to conducting less than 
minimal risk and exempt research. In addition, commenters raised 
concerns about the administrative burden and need for a retrospective 
audit system of registered research.
    Exemption Categories: The ANPRM considered revising the regulations 
regarding studies currently considered exempt by expanding the current 
exemption category 2 (research involving educational tests, surveys, 
focus groups, interviews, and similar procedures, found in the current 
Rule at Sec.  __.101(b)(2)) to include all studies involving 
educational tests, surveys, interviews, and similar procedures so long 
as the subjects are competent adults, without any further 
qualifications. It also considered adding a new category for certain 
types of behavioral and social science research that goes beyond using 
only survey methodology, but nonetheless involves only specified 
minimal risk procedures, so long as the subjects are competent adults 
(but subject to the data security and information protection 
standards). The term ``competent'' as used in the ANPRM referred to 
adults who would be able to provide ``legally effective informed 
consent,'' as currently required by Sec.  __.116.\102\
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    \102\ Informed consent is legally effective if, in part, it is 
both obtained from the subject or the subject's legally authorized 
representative and documented in a manner that is consistent with 
the HHS protection of human subjects regulations and with applicable 
laws of the jurisdiction in which the research is conducted. See 
Office for Human Research Protections. (2011, January 20). What is 
the meaning of ``legally effective informed consent?''. Retrieved 
from Frequently Asked Questions: http://www.hhs.gov/ohrp/policy/faq/informed-consent/what-is-legally-effective-informed-consent.html.
---------------------------------------------------------------------------

    The ANPRM also considered whether to include on the list of exempt 
studies certain types of social and behavioral research conducted with 
competent adults that would involve specified types of benign 
interventions commonly used in social and behavioral research, that are 
known to involve virtually no risk to subjects, and for which prior 
review does little to increase protections to subjects. These would be 
methodologies that are familiar to people in everyday life and in which 
verbal or similar responses would constitute the research data being 
collected. For example, an investigator might ask subjects to watch a 
video, read a paragraph, or solve puzzles, and then ask them some 
questions to elicit word associations or time performance of 
activities. The specific methodologies might be spelled out in 
regulations, or they might be promulgated via a periodic mechanism to 
announce and update lists similar to the list that is published for 
activities that may be reviewed by an IRB using the expedited review 
procedures.\103\
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    \103\ 63 FR 60364 (Nov 9, 1998). Also available at, http://www.hhs.gov/ohrp/policy/expedited98.html.
---------------------------------------------------------------------------

    A majority of commenters supported the ANPRM discussion on 
expanding current exemption category 2 (current Rule at Sec.  
__.101(b)(2)) by eliminating the limitations related to the recording 
of identifiable information and the harm that could result if a 
subject's responses were disclosed. However, many commenters were 
opposed to the requirement that subjects be ``competent adults'' in 
order for the expanded exemption to apply, asking whether tests of 
competency would be required for such research to proceed.
    Many commenters also supported adding another exemption category of 
research for certain types of social and behavioral activities, 
conducted with competent adults, that would involve specified types of 
benign interventions beyond educational tests, surveys, focus groups, 
interviews, and similar procedures that are commonly used in social and 
behavioral research, that are known to involve virtually no risk to 
subjects, and for which IRB review does little to increase protections 
for subjects.
    The ANPRM asked questions about whether the current limitations 
specified in exempt category 4 (research involving the use of existing 
information or biospecimens, Sec.  __.101(b)(4) in the current Rule) 
should be eliminated. Specifically, the ANPRM suggested that the 
category would be revised to eliminate the word ``existing.'' With this 
elimination, the exemption would be broadened to cover the use of 
information or biospecimens that were or will be collected for purposes 
other than the suggested research, rather than requiring that all of 
the information or biospecimens already exist at the time the study is 
suggested for exemption.
    The ANPRM also discussed whether research involving only the use of 
data or biospecimens collected for other purposes, even if the 
investigator intends to retain identifiers, should come within a new 
exemption category; studies that include a plan to provide individual 
research results to subjects would not qualify for this proposed 
exemption. In addition, the ANPRM asked whether certain flexible 
consent requirements could be imposed on some of these studies that 
would permit the use of a broad consent for future use, with a 
requirement that a subject's specific consent would be required before 
their biospecimens could be used for special categories of research.
    Many of the comments supported the discussion in the ANPRM of 
eliminating the requirement that the information or biospecimens be 
``existing'' at the time the study was suggested for exemption. 
However, a majority strongly disagreed that biospecimens should be 
considered or treated as though they were inherently identifiable. A 
majority also opposed the suggestion that there be consent requirements 
for the research use of nonidentifiable biospecimens collected for 
purposes other than the current research study.
    Some commenters also favored requiring IRB review and approval for 
the use of identifiable private information and identifiable 
biospecimens, rather than permitting the use of a broad consent for 
future use to satisfy the regulatory requirement for consent. These 
commenters indicated that IRB review of specific research studies, and 
the IRB's consideration of whether a study specific informed consent 
should be required or whether informed consent could be waived, was 
more protective of human subjects than the ANPRM recommendation of 
permitting use of a broad consent for future use.
    The ANPRM asked several questions about the interpretation and 
applicability of current exemption category 5 (current Rule at

[[Page 54042]]

Sec.  __.101(b)(5)), including the scope of the current interpretation 
of the category 5 exemption. The ANPRM also asked if the current 
category 5 guidance entitled, ``OPRR Guidance on 45 CFR 46.101(b)(5)'' 
\104\ should be revised, or if additional guidance on the 
interpretation of exemption category 5 is needed.
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    \104\ See 48 FR 9266-9270 (Mar 4, 1983). (OPRR Guidance on 45 
CFR 46.101(b)(5), Exemption for Research and Demonstration Projects 
on Public Benefit and Service Programs, http://www.hhs.gov/ohrp/policy/exmpt-pb.html).
---------------------------------------------------------------------------

    There were few responses to these questions. However, those that 
did comment noted that this category is often misunderstood by IRBs 
and, at best, would benefit from clearer guidance. Commenters said that 
examples would help investigators and IRBs understand when research 
activities included in demonstration projects constitute human subjects 
research subject to the Common Rule. Commenters noted that many 
activities in demonstration projects do not contribute to generalizable 
knowledge as they produce results that are relevant only to the program 
being assessed; as such, many of these activities do not meet the 
Common Rule's regulatory definition of ``research'' and thus fall 
outside of the rule. Other commenters said that some activities in this 
category are mandated or required by law or regulation and should not 
be considered to be under the purview of the Common Rule. It was noted 
that the critical issue in these studies should be protecting privacy 
and as long as measures are in place to do so, additional protections 
are not required.
3. Expedited Review
    The ANPRM discussed and sought comment on three possible changes to 
the review of research through expedited review: (1) Revising the 
definition of minimal risk, which is one of the criteria for 
determining whether a study is eligible for expedited review; (2) 
changing the default position so that research on the expedited review 
list could generally be presumed to involve minimal risk; (3) revising 
the criteria for approval of research studies under expedited review; 
and (4) allowing appropriately trained individuals who are not IRB 
members to conduct expedited reviews.
    Definition of Minimal Risk: The ANPRM asked for public comment on 
whether the current regulatory definition of minimal risk \105\ was 
appropriate. The definition of minimal risk has relevance to 
determining whether a protocol is eligible for expedited review. Public 
comments expressed both a desire to retain the current definition 
(slightly less than half) and a desire for changing it (slightly more 
than half). There were few common themes in the suggested changes to 
the language other than seeking clarification on what baselines an IRB 
should consider in determining the meaning of ``daily life'' and 
``routine physical or psychological examinations.'' Several commenters 
acknowledged the difficulty of arriving at a concise definition for all 
circumstances. Those opposed to changing the definition said that IRBs 
generally understand how to interpret the language and that difficult 
or challenging application of the definition will persist regardless of 
the definition for those areas of research where risks are difficult to 
assess. Commenters recognized that the risks encountered in daily life 
can vary greatly depending on many factors, for example, where people 
live, what kind of work they are involved in, what their social and 
economic environment is, and their baseline health status. Thus, IRBs 
need to consider all of these issues in making a determination about 
the level of risk.
---------------------------------------------------------------------------

    \105\ The current rule states that minimal risk means that the 
probability and magnitude of harm or discomfort anticipated in the 
research are not greater in and of themselves than those ordinarily 
encountered in daily life or during the performance of routine 
physical or psychological examinations or tests. (45 CFR 46.102(i)).
---------------------------------------------------------------------------

    Eligibility for Expedited Review: The ANPRM suggested updating the 
current list of research activities eligible for expedited review; this 
list was last updated in 1998. It also considered mandating that a 
federal panel periodically (such as every year or every two years) 
review and update the list, based on a systematic, empirical assessment 
of the levels of risk. This would provide greater clarity about what 
would be considered to constitute minimal risk, and create a process 
that allows for routinely reassessing and updating the list of research 
activities that would qualify as minimal risk. The ANPRM asked for 
public comments on categories of research that should be considered for 
addition to the current list.
    Several commenters provided suggestions for additions to the list 
of research activities eligible for expedited review. Others encouraged 
OHRP to consider developing principles for expedited review, rather 
than creating a revised list of research activities. Commenters 
suggested a more timely and consistent review of the list because of 
the rapidly changing state of science and technology.
    The ANPRM also discussed the potential adoption of a default 
presumption in the rule that a study that includes only activities on 
the expedited review list is a minimal risk study and should receive 
expedited review. A reviewer would have the option of determining that 
the study should be reviewed by a convened IRB when that conclusion is 
supported by the specific circumstances of the study. The ANPRM also 
asked for comments on whether IRBs should be required to report 
instances when they overrode the default presumption that research 
appearing on the posted list did not warrant review by a convened IRB.
    Commenters overwhelmingly welcomed the clarification that 
categories of research found on the published list should be presumed 
to be minimal risk. However, commenters were largely opposed to 
requiring IRBs to report instances when they conducted a review by the 
convened membership (versus an expedited review) for studies appearing 
on the list. They were opposed because of the additional administrative 
burden and also because they felt such a requirement would undermine 
the purview of local review and open IRBs up to second-guessing by 
OHRP.
    Criteria for Approval under Expedited Review: The ANPRM asked 
whether all of the Sec.  __.111 criteria should still be required for 
approval of studies that qualify for expedited review, and if not, 
which ones should not be required. Currently, before an IRB may approve 
a research study, including research that is being reviewed under an 
expedited procedure, the IRB must find that the criteria at Sec.  
__.111 have been met.
    With regard to revising the criteria used for expedited review, 
comments were mixed. Nearly half of those commenting expressed concerns 
about establishing two sets of ethical standards for IRB review--one 
for convened review and one for expedited review. They asserted ethical 
and administrative concerns about operating under two sets of 
conditions and principles--that is, expedited review should not be 
viewed as less stringent than review conducted by a convened IRB.
    Those commenters in favor of retaining the current criteria wrote 
that a double standard could result in arbitrary IRB decision making. 
In addition, many wrote that the current criteria are well understood 
by IRB members and the tendency to review a protocol through a convened 
IRB when expedited review would be permissible is more a function of 
institutional

[[Page 54043]]

concerns about liability than the regulatory requirements. They cited 
the regulatory language at Sec.  __.111, which frequently contains the 
phrase ``wgeb appropriate,'' so that the reviewer(s) can exercise 
discretion in whether all of the criteria need to be applied.
    Those in favor of revising the elements most often cited the 
irrelevance of some of the criteria for minimal risk research, such as 
the need to ensure that risks to subjects are reasonable in relation to 
anticipated benefits (Sec.  __.111)(a)(2)). They stated that in the 
case of minimal risk research, the need to balance risks with benefits 
is not pertinent. Some commenters asked OHRP to develop guidance for 
the expedited reviewer in interpreting the most relevant criteria 
during expedited review.
    Several commenters noted that if the revised regulations remove the 
requirement for continuing review of studies initially reviewed through 
expedited review it would alleviate administrative burden; thus more 
extreme measures such as revising the review criteria would be less 
compelling.
    Who May Conduct Expedited Reviews: The ANPRM asked for public 
comment on the advantages and disadvantages of requiring that expedited 
review be conducted by an IRB member versus an appropriately trained 
individual, such as the manager of the IRB office, who need not be a 
member of the IRB.
    With regard to allowing a non-IRB member to conduct expedited 
review, comments were divided nearly evenly between those who opposed 
such a change and those who supported it. Those who opposed it cited 
the need for continuity and consistency across IRBs, as well as 
expressing concerns about accountability and liability. Those in favor 
of such a revision cited the expertise of IRB staff members and their 
ability to review many expedited studies at the same level as a member 
of the IRB.
4. Streamlining IRB Review
    Cooperative Research: The ANPRM sought public comment on the 
feasibility, advantages, and disadvantages of mandating that all 
domestic (U.S.) sites in a study involving more than one institution 
rely on a single IRB for that study. This would apply regardless of 
whether the study underwent convened review or expedited review. 
Further, it would only affect which IRB would be designated as the 
reviewing IRB for institutional compliance with the IRB review 
requirements of the Common Rule. It would not relieve any site of its 
other obligations under the regulations to protect human subjects. Nor 
would it prohibit institutions from choosing, for their own purposes, 
to conduct additional internal ethics reviews, though such reviews 
would no longer have any regulatory status in terms of compliance with 
the Common Rule.
    To address institutions' concerns about OHRP's practice of 
enforcing compliance with the Common Rule through the institutions that 
are engaged in human subjects research, the ANRPM also suggested that 
appropriate accompanying changes could be made in enforcement 
procedures to hold external IRBs directly accountable for compliance 
with certain regulatory requirements.\106\ This change was discussed 
only for U.S. sites in multi-institutional studies. The ANPRM suggested 
that, in most cases, independent local IRB reviews of international 
sites are appropriate because it might be difficult for an IRB in the 
U.S. to adequately evaluate local conditions in a foreign country that 
could play an important role in the ethical evaluation of the study.
---------------------------------------------------------------------------

    \106\ 74 FR 9578 (Mar. 5, 2009). Also available at http://www.hhs.gov/ohrp/newsroom/rfc/com030509.html.
---------------------------------------------------------------------------

    This issue attracted a large number of comments, and revealed 
nearly evenly divided perspectives. Researchers and disease advocacy 
groups tended to favor the single IRB review requirement. IRB and 
institutional representatives tended to be opposed to the possible 
requirement, though many indicated single IRB review should be 
encouraged. Support was especially strong for single IRB review for 
cooperative clinical trials for which the evaluation of a study's 
social value, scientific validity, and risks and benefits, and the 
adequacy of the informed consent form and process generally do not 
require the unique perspective of a local IRB. Moreover, depending on 
the nature of the study, FDA may not permit differences in protocols 
across sites, which further bolstered commenters' views that the 
requirements be harmonized across the Common Rule and FDA requirements. 
Commenters reported incidences of IRBs continuously second-guessing 
each other, which delayed studies to the point that subject recruitment 
opportunities were foregone or lost. This problem seemed especially 
critical in studies of rare diseases and cancers, which nearly always 
involve multiple research sites.
    Support for the use of a single IRB, however, was not restricted to 
clinical trials. Several commenters cited long delays and burdensome 
requirements resulting from multiple reviews of studies in the 
behavioral and social sciences. In addition to the view that these 
administrative requirements do not enhance protections, supporters of a 
single IRB review of cooperative studies cited the frequent need for 
maintaining consistency across sites, which can be degraded by multiple 
reviews.
    Despite support for the ANPRM suggestion, several commenters 
expressed concern about making such a provision mandatory, stating that 
the current regulations at Sec.  __.114 currently permit the use of 
joint review arrangements for cooperative research. They noted that 
although this option exists, institutions might be hesitant to use it 
because of liability concerns and the unwillingness of institutions or 
IRBs to rely on the judgment of other institutions or IRBs. However, 
several commenters expressed concern about signaling the acceptability 
of a single IRB for review while allowing institutions to continue to 
conduct their own ethics review, fearing that such a policy would not 
correct the current situation, which tends to favor multiple reviews. 
Thus, they commented that mandating a single IRB might be the only way 
to achieve the goals of streamlining review while ensuring protections.
    Another issue raised was the need to set clearer expectations of 
the responsibilities of local IRBs that are not designated as the 
central IRB. A number of commenters supporting the requirement for a 
central IRB also requested that OHRP issue guidance on how to select 
the IRB, responsibilities of all parties, and clarifying compliance and 
enforcement policies. Several commenters also requested that OHRP 
develop a template for reliance agreements to replace inter-
institutional agreements currently in use.
    Those who expressed concern about the use of a single IRB said some 
studies, especially in the behavioral and social sciences, might 
involve significant contextual issues reflecting community norms, 
standards, and practices, or local culture and customs. Use of a 
distant IRB might not consider and best protect subjects based on 
community norms. Others noted that such concerns can be addressed by 
investigators or IRBs submitting ``points to consider'' regarding 
significant contextual or cultural considerations of relevance to their 
site.
    A primary issue posed by those opposed to mandating use of a single 
IRB in cooperative studies focused on potential loss of accountability 
and increased liability for the institutions

[[Page 54044]]

where the research is conducted but where the reviewing IRB is not 
located.
    Streamlining Documentation Requirements for Expedited Studies: 
Under the current Common Rule, investigators typically must submit the 
same documents including a detailed protocol, informed consent forms, 
and any other supporting documents, regardless of whether the study 
will be reviewed by a convened IRB or be approved by the expedited 
review process. The ANPRM suggested that although it is important to 
document why research qualifies for expedited review, it is unclear 
whether the time and effort expended in such preparation activities 
result in increased benefit in terms of protecting subjects.
    The ANPRM further suggested that standard templates for protocols 
and consent forms and sample versions of those documents that are 
specifically designed for use in the most common types of studies might 
facilitate expedited review. Such forms would need to be carefully 
designed to eliminate those elements that are of relevance only in 
studies that pose greater than minimal risks and to substantially 
reduce the current burden of researchers involved in producing these 
documents and of the IRB members who review them. The ANPRM asked 
whether there were specific changes that could be made to reduce the 
burden imposed on investigators and their staffs in terms of meeting 
the requirements to submit documents to an IRB, without decreasing 
protections to subjects.
    There were few comments on streamlining the document submission 
requirements for expedited review, and there was no consensus among 
those who did comment about how to achieve that goal.
    Continuing Review: The ANPRM asked for public comments on 
eliminating continuing review for all minimal risk studies that undergo 
expedited review, unless the reviewer explicitly justifies why 
continuing review would enhance protection of research subjects.
    Additionally, the ANPRM suggested that, for studies initially 
reviewed by a convened IRB, continuing review would not be required 
after the study reaches the stage where procedures are limited to 
either: (1) Analyzing data (even if it is identifiable), or (2) 
accessing follow-up clinical data from procedures that subjects would 
undergo as part of standard care for their medical condition or disease 
(such as periodic CT scans to monitor whether the subjects' cancers 
have recurred or progressed) unless specifically mandated by the IRB,. 
This would be a change from the current Rules, which require at least 
expedited IRB review of the activities described in (1) and (2) above. 
The requirement that research involving greater than minimal risk be 
reviewed by a convened IRB would not be changed from the current 
system.
    By eliminating the requirement for continuing review of these 
activities, the ANPRM suggested that this change would allow for more 
effective use of IRBs' time by enabling the IRB to focus on reviewing 
information that is necessary to ensure protection of research 
subjects. Requiring annual continuing review of research studies 
involving only activities that are already well-documented to generally 
involve no more than minimal risk may provide little if any added 
protection to subjects, and it may be preferable for IRB resources to 
be devoted to research that poses greater than minimal risk.
    The ANPRM asked for public comment on whether it would be 
appropriate to require IRBs to submit periodic reports to OHRP in the 
instances in which they choose to override the default policy of no 
continuing review required for the situations described above. The 
information, if collected by OHRP, might be useful in developing future 
guidance or revising the categories of research eligible for expedited 
review.
    A large majority of public comments were in favor of the suggested 
revisions. Many were comfortable with continuing to allow IRBs or 
reviewers the discretion to require continuing review in certain 
circumstances, citing the historical position of OHRP in considering 
the regulations as the floor, rather than the ceiling, for protecting 
the subjects of research. Those who were opposed to the revisions cited 
concerns about institutional liability, the possibility for increased 
noncompliance among investigators no longer required to ``check in,'' 
and possible breakdowns in lines of communications between 
investigators and IRBs. Others expressed concerns about how an IRB will 
know that a study has ended and suggested that investigators be 
required to file a notice of closure of a study.
    Note that the November 10, 2010, document entitled, ``Guidance on 
IRB Continuing Review of Research'' states:

    OHRP is aware that many IRBs require investigators to submit 
final closeout reports when a research study is completed or no 
longer involves human subjects. Since the HHS regulations at 45 CFR 
part 46 do not require submission of such reports, institutions are 
free to decide whether and when such reports are required and what 
their content should include.\107\
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    \107\ Office for Human Research Protections. (2010, November 
10). Identifying the Point When Continuing Review is no Longer 
Necessary. Retrieved from Guidance on IRB Continuing Review of 
Research: http://www.hhs.gov/ohrp/policy/continuingreview2010.html#section-k.

    Commenters overwhelmingly opposed requiring IRBs to periodically 
report on the instances when they (or a reviewer) elect to override the 
default position of no continuing review required. The reasons for 
opposition included: (1) Additional administrative burden that would 
negate the reduced burden gained; (2) the possibility that requiring 
such reporting would discourage IRBs/reviewers from making an override 
decision; and (3) concerns that such reports would lead to OHRP second-
guessing IRB decisions and imposing compliance oversight in an extra-
regulatory decision. Several commenters suggested that OHRP could use 
other means than this requirement for developing guidance and improving 
educational efforts regarding expedited and continuing review.
5. Improving Harmonization
    The ANPRM did not suggest any specific approaches to harmonization 
but asked for public comment on a set of questions focused on: (1) The 
extent to which differences in guidance on research protections from 
different agencies strengthen or weaken protections for human subjects; 
(2) the extent to which differences in guidance on research protections 
from different agencies facilitate or inhibit the conduct of research 
domestically and internationally; and (3) the desirability of all 
Common Rule agencies issuing one set of guidance.
    Responses to questions about the need for harmonization across 
Common Rule agencies reflected widespread support for such efforts. 
Several commenters acknowledged the difficulty of getting all Common 
Rule agencies to agree on all issues, as each has a different mission 
and research portfolio. However, they encouraged seeking harmonized 
guidance whenever possible.

Regulatory Text

    For the reasons set forth in the preamble, it is proposed that the 
Federal Policy for the Protection of Human Subjects be amended as 
follows:

PART __PROTECTION OF HUMAN SUBJECTS

__.101 To what does this policy apply?
__.102 Definitions for purposes of this policy.

[[Page 54045]]

__.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
__.104 Exempt research.
__.105 Protection of biospecimens and identifiable private 
information.
__.106 [Reserved]
__.107 IRB membership.
__.108 IRB functions and operations.
__.109 IRB review of research.
__.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
__.111 Criteria for IRB approval of research.
__.112 Review by institution.
__.113 Suspension or termination of IRB approval of research.
__.114 Cooperative research.
__.115 IRB records.
__.116 General requirements for informed consent.
__.117 Documentation of informed consent.
__.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
__.119 Research undertaken without the intention of involving human 
subjects.
__.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
__.121 [Reserved]
__.122 Use of Federal funds.
__.123 Early termination of research support: Evaluation of 
applications and proposals.
__.124 Conditions.


Sec.  __.101  To what does this policy apply?

    (a) Except as provided in paragraph (b) of this section, and as 
detailed in Sec.  __.104, this policy applies to the research described 
in paragraphs (a)(1) and (2) of this section. The entities that must 
comply with this policy are institutions that are engaged in research 
described in paragraphs (a)(1) or (2) of this section, and 
institutional review boards (IRBs) reviewing research that is subject 
to this policy.
    (1) All research involving human subjects conducted, supported, or 
otherwise subject to regulation by any Federal department or agency 
that takes appropriate administrative action to make the policy 
applicable to such research. This includes research conducted by 
Federal civilian employees or military personnel, except that each 
department or agency head may adopt such procedural modifications as 
may be appropriate from an administrative standpoint. It also includes 
research conducted, supported, or otherwise subject to regulation by 
the Federal Government outside the United States.
    (2) All clinical trials as defined by this policy, irrespective of 
funding source, that meet all of the following conditions:
    (i) The clinical trials are conducted by an institution that 
receives support from a Federal department or agency for human subjects 
research that is not excluded from this policy under Sec.  __.101(b)(2) 
and does not qualify for exemption in accordance with Sec.  __.104;
    (ii) The clinical trials are not subject to regulation by the Food 
and Drug Administration; and
    (iii) The clinical trials are conducted at an institution located 
within the United States.\1\
---------------------------------------------------------------------------

    \1\ Under this provision, only 45 CFR part 46, subpart A, 
applies to all clinical trials meeting the applicable conditions. 
This provision does not require clinical trials to comply with the 
requirements of 45 CFR part 46, subparts B, C, and D.
---------------------------------------------------------------------------

    (b) The following categories of activities are excluded from this 
policy, and no procedural, recordkeeping, or other requirements of this 
policy apply to the activities other than the conditions specified for 
the relevant category or categories:
    (1) The following activities are excluded because they are deemed 
not to be research, as defined in Sec.  __.102(l), for the purposes of 
this regulation:
    (i) Data collection and analysis, including the use of 
biospecimens, for an institution's own internal operational monitoring 
and program improvement purposes, if the data collection and analysis 
is limited to the use of data or biospecimens originally collected for 
any purpose other than the currently proposed activity, or is obtained 
through oral or written communications with individuals (e.g., surveys 
or interviews).
    (ii) Oral history, journalism, biography, and historical 
scholarship activities that focus directly on the specific individuals 
about whom the information is collected.
    (iii) Collection and analysis of data, biospecimens, or records by 
or for a criminal justice agency for activities authorized by law or 
court order solely for criminal justice or criminal investigative 
purposes.
    (iv) Quality assurance or improvement activities involving the 
implementation of an accepted practice to improve the delivery or 
quality of care or services (including, but not limited to, education, 
training, and changing procedures related to care or services) if the 
purposes are limited to altering the utilization of the accepted 
practice and collecting data or biospecimens to evaluate the effects on 
the utilization of the practice. This exclusion does not cover the 
evaluation of an accepted practice itself.
    (v) Public health surveillance activities, including the collection 
and testing of biospecimens, conducted, supported, requested, ordered, 
required, or authorized by a public health authority and limited to 
those necessary to allow the public health authority to identify, 
monitor, assess, or investigate potential public health signals or the 
onset of a disease outbreak, including trends, or signals, and patterns 
in diseases, or a sudden increase in injuries from using a consumer 
product, or conditions of public health importance, from data, and 
including those associated with providing timely situational awareness 
and priority setting during the course of an event or crisis that 
threatens public health, including natural or man-made disasters.
    (vi) Surveys, interviews, surveillance activities and related 
analyses, or the collection and use of biospecimens conducted by a 
defense, national security, or homeland security authority solely for 
authorized intelligence, homeland security, defense, or other national 
security purposes.
    (2) The following activities are excluded because they are 
considered to be low-risk human subjects research, when already subject 
to independent controls without application of these regulatory 
requirements. These exclusions do not apply when the research includes 
the collection or analysis of biospecimens. All of the following 
exclusion categories apply to research subject to this policy and to 
research subject to the additional requirements of 45 CFR part 46, 
subparts B, C, and D, however, the exclusion at paragraph (b)(2)(i) of 
this section applies only to research subject to subpart D for research 
involving educational tests, or observations of public behavior when 
the investigator does not participate in the activities being observed.
    (i) Research, not including interventions, that involves the use of 
educational tests (cognitive, diagnostic, aptitude, achievement), 
survey procedures, interview procedures, or observation of public 
behavior (including visual or auditory recording) uninfluenced by the 
investigators, if at least one of the following criteria is met:
    (A) The information is recorded by the investigator in such a 
manner that human subjects cannot be identified, directly or through 
identifiers linked to the subjects;
    (B) Any disclosure of the human subjects' responses outside the 
research would not reasonably place the subjects

[[Page 54046]]

at risk of criminal or civil liability or be damaging to the subjects' 
financial standing, employability, educational advancement, or 
reputation; or
    (C) The research will involve a collection of information subject 
to the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq.; 
research information will be maintained on information technology that 
is subject to and in compliance with section 208(b) of the E-Government 
Act of 2002, 44 U.S.C. 3501 note; and all of the information collected, 
used, or generated as part of the research will be maintained in a 
system or systems of records subject to the Privacy Act of 1974, 5 
U.S.C. 552a.
    (ii) Research involving the collection or study of information that 
has been or will be acquired solely for non-research activities or were 
acquired for research studies other than the proposed research study, 
when either of the following two criteria is met:
    (A) These sources are publicly available, or
    (B) The information is recorded by the investigator in such a 
manner that human subjects cannot be identified, directly or through 
identifiers linked to the subjects, the investigator does not contact 
the subjects, and the investigator will not re-identify subjects or 
otherwise conduct an analysis that could lead to creating identifiable 
private information.
    (iii) Research conducted by a Federal department or agency using 
government-generated or government-collected information obtained for 
non-research purposes (including criminal history data), if the 
information originally involved a collection of information subject to 
the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq.; the 
information is maintained on information technology that is subject to 
and in compliance with section 208(b) of the E-Government Act of 2002, 
44 U.S.C. 3501 note; and all of the information collected, used, or 
generated as part of the research is maintained in a system or systems 
of records subject to the Privacy Act of 1974, 5 U.S.C. 552a.
    (iv) Research as defined by this policy that involves only data 
collection and analysis involving the recipient's use of identifiable 
health information when such use is regulated under 45 CFR parts 160 
and 164, subparts A and E, for the purposes of ``health care 
operations'' or ``research'' as those terms are defined at 45 CFR 
164.501 or for the purpose of ``public health activities'' as described 
under 45 CFR 164.512(b).
    (3) The following activities are excluded because they are 
considered to be low-risk human subjects research activities that do 
not meaningfully diminish subject autonomy. The following exclusion 
category applies to research subject to this policy and to research 
subject to the additional requirements of 45 CFR part 46, subparts B, 
C, or D.
    (i) The secondary research use of a non-identified biospecimen that 
is designed only to generate information about an individual that 
already is known, including but not limited to the development and 
validation of certain tests and assays (such as research to develop a 
diagnostic test for a condition using specimens from individuals known 
to have the condition and those known not to have the condition), 
quality assurance and control activities, and proficiency testing.
    (ii) [Reserved]
    (c) Department or agency heads retain final judgment as to whether 
a particular activity is covered by this policy, which judgment shall 
be exercised consistent with the ethical principles of the Belmont 
Report.\2\
---------------------------------------------------------------------------

    \2\ The National Commission for the Protection of Human Subjects 
of Biomedical and Behavioral Research, The Belmont Report: Ethical 
Principles and Guidelines for the Protection of Human Subjects of 
Research (Apr. 18, 1979).
---------------------------------------------------------------------------

    (d) Department or agency heads may require additional protections 
for specific research activities or classes of research activities 
conducted, supported, or otherwise subject to regulation by the Federal 
department or agency but not otherwise covered by this policy. Advance 
public notice will be required when those additional requirements apply 
to entities outside of the Federal department or agency itself.
    (e) Compliance with this policy requires compliance with pertinent 
federal laws or regulations that provide additional protections for 
human subjects.
    (f) This policy does not affect any state or local laws or 
regulations that may otherwise be applicable and that provide 
additional protections for human subjects.
    (g) This policy does not affect any foreign laws or regulations 
that may otherwise be applicable and that provide additional 
protections to human subjects of research.
    (h) When research covered by this policy takes place in foreign 
countries, procedures normally followed in the foreign countries to 
protect human subjects may differ from those set forth in this policy. 
In these circumstances, if a department or agency head determines that 
the procedures prescribed by the institution afford protections that 
are at least equivalent to those provided in this policy, the 
department or agency head may approve the substitution of the foreign 
procedures in lieu of the procedural requirements provided in this 
policy. Except when otherwise required by statute, Executive Order, or 
the department or agency head, notices of these actions as they occur 
will be published in the Federal Register or will be otherwise 
published as provided in department or agency procedures.
    (i) Unless otherwise required by law, department or agency heads 
may waive the applicability of some or all of the provisions of this 
policy to specific research activities or classes of research 
activities otherwise covered by this policy provided the alternative 
procedures to be followed are consistent with the principles of the 
Belmont Report.\3\ Except when otherwise required by statute or 
Executive Order, the department or agency head shall forward advance 
notices of these actions to the Office for Human Research Protections, 
Department of Health and Human Services (HHS), or any successor office, 
or to the equivalent office within the appropriate Federal department 
or agency, and shall also publish them in the Federal Register or in 
such other manner as provided in department or agency procedures. The 
waiver notice must include a statement that identifies the conditions 
under which the waiver will be applied and a justification as to why 
the waiver is appropriate for the research, including how the decision 
is consistent with the principles in Belmont Report. Each Federal 
department or agency conducting or supporting the research must 
establish, on a publicly accessible federal Web site, a list of the 
research for which a waiver has been issued.
---------------------------------------------------------------------------

    \3\ Id.
---------------------------------------------------------------------------

    (j) Federal guidance on the requirements of this policy shall be 
issued only after consultation, for the purpose of harmonization (to 
the extent appropriate), with other Federal departments and agencies 
that have adopted this policy, unless such consultation is not 
feasible.
    (k) Transition provisions--(1) Research initiated prior to the 
compliance dates. Ongoing human subjects research in which human 
subjects (as defined by this policy) were involved prior to the 
compliance dates for the cited provisions need not comply with the 
additional requirements of this subpart at Sec. Sec.  __.101(a)(2), 
__.103(e), __.104(c) through (f), __.105, __.108(a)(2), __.109(f)(2), 
__.111(a)(7) and (8), __.114, __.115(a)(10) and (11), __.116, and 
__.117 that became effective on [effective date of the final rule].

[[Page 54047]]

    (2) Use of prior collections of biospecimens. Research involving 
the use of prior collections of biospecimens that meets both of the 
following criteria need not comply with the requirements of these 
regulations:
    (i) The biospecimens were collected for either research or non-
research purposes before the compliance date for the additional 
requirements of this subpart at Sec.  __.102(e)(1)(iii), and
    (ii) Research use of the biospecimens occurs only after removal of 
any individually identifiable information associated with the 
biospecimens.


Sec.  __.102  Definitions for purposes of this policy.

    (a) Certification means the official notification by the 
institution to the supporting Federal department or agency component, 
in accordance with the requirements of this policy, that a research 
project or activity involving human subjects has been reviewed and 
approved by an IRB in accordance with an approved assurance.
    (b) Clinical trial means a research study in which one or more 
human subjects are prospectively assigned to one or more interventions 
(which may include placebo or other control) to evaluate the effects of 
the interventions on biomedical or behavioral health-related outcomes.
    (c) Department or agency head means the head of any Federal 
department or agency, for example, the Secretary, HHS, and any other 
officer or employee of any Federal department or agency to whom the 
authority provided to the department or agency head by these 
regulations has been delegated.
    (d) Federal department or agency refers to a Federal department or 
agency (the department or agency itself rather than its bureaus, 
offices or divisions) that takes appropriate administrative action to 
make this policy applicable to the research involving human subjects it 
conducts, supports, or otherwise regulates (e.g., HHS, the Department 
of Defense, or the Central Intelligence Agency).
    (e)(1) Human subject means a living individual about whom an 
investigator (whether professional or student) conducting research:
    (i) Obtains data through intervention or interaction with the 
individual, and uses, studies, or analyzes the data;
    (ii) Obtains, uses, studies, analyzes, or generates identifiable 
private information; or
    (iii) Obtains, uses, studies, or analyzes biospecimens.
    (2) Intervention includes both physical procedures by which data 
are gathered (e.g., venipuncture) and manipulations of the subject or 
the subject's environment that are performed for research purposes.
    (3) Interaction includes communication or interpersonal contact 
between investigator and subject.
    (4) Private information includes information about behavior that 
occurs in a context in which an individual can reasonably expect that 
no observation or recording is taking place, and information that has 
been provided for specific purposes by an individual and that the 
individual can reasonably expect will not be shared or made public 
(e.g., a medical record or clinically obtained biospecimen).
    (5) Identifiable private information is private information that is 
individually identifiable (i.e., the identity of the subject is or may 
readily be ascertained by the investigator or associated with the 
information).
    (f) Institution means any public or private entity, or department 
or agency (including federal, state, and other agencies).
    (g) IRB means an institutional review board established in accord 
with and for the purposes expressed in this policy.
    (h) IRB approval means the determination of the IRB that the 
research has been reviewed and may be conducted at an institution 
within the constraints set forth by the IRB and by other institutional 
and federal requirements.
    (i) Legally authorized representative means an individual or 
judicial or other body authorized under applicable law to consent on 
behalf of a prospective subject to the subject's participation in the 
procedure(s) involved in the research.
    (j) Minimal risk means that the probability and magnitude of harm 
or discomfort anticipated in the research are not greater in and of 
themselves than those ordinarily encountered in daily life or during 
the performance of routine physical or psychological examinations or 
tests. The Secretary of HHS will maintain guidance that includes a list 
of activities considered to involve no more than minimal risk. This 
list will be re-evaluated no later than every 8 years based on 
recommendations from the Federal departments and agencies and the 
public.
    (k) Public health authority (consistent with 45 CFR 164.501) means 
an agency or authority of the United States, a state, a territory, a 
political subdivision of a state or territory, an Indian tribe, or a 
foreign government, or a person or entity acting under a grant of 
authority from or contract with such public agency, including the 
employees or agents of such public agency or its contractors or persons 
or entities to whom it has granted authority, that is responsible for 
public health matters as part of its official mandate.
    (l) Research means a systematic investigation, including research 
development, testing, and evaluation, designed to develop or contribute 
to generalizable knowledge. Activities that meet this definition 
constitute research for purposes of this policy, whether or not they 
are conducted or supported under a program that is considered research 
for other purposes. For example, some demonstration and service 
programs may include research activities.


Sec.  __.103  Assuring compliance with this policy--research conducted 
or supported by any Federal department or agency.

    (a) Each institution engaged in research that is covered by this 
policy, with the exception of research excluded from this policy under 
Sec.  __.101(b) or eligible for exemption under Sec.  __.104(d), and 
that is conducted or supported by a Federal department or agency shall 
provide written assurance satisfactory to the department or agency head 
that it will comply with the requirements of this policy. In lieu of 
requiring submission of an assurance, individual department or agency 
heads shall accept the existence of a current assurance, appropriate 
for the research in question, on file with the Office for Human 
Research Protections, HHS, or any successor office, and approved for 
federalwide use by that office. When the existence of an HHS-approved 
assurance is accepted in lieu of requiring submission of an assurance, 
reports (except certification) required by this policy to be made to 
department and agency heads shall also be made to the Office for Human 
Research Protections, HHS, or any successor office. Federal departments 
and agencies will conduct or support research covered by this policy 
only if the institution has provided an assurance that it will comply 
with the requirements of this policy, as provided in this section, and 
only if the institution has certified to the department or agency head 
that the research has been reviewed and approved by an IRB.
    (b) The assurance shall be executed by an individual authorized to 
act for the institution and to assume on behalf of the institution the 
obligations imposed by this policy and shall be filed in such form and 
manner as the department or agency head prescribes.
    (c) The department or agency head may limit the period during which 
any assurance shall remain effective or

[[Page 54048]]

otherwise condition or restrict the assurance.
    (d) Certification is required when the research is supported by a 
Federal department or agency and not otherwise excluded under Sec.  
__.101(b), waived under Sec.  __.101(i), or exempted under Sec.  
__.104(d), (e), or (f)(2). Institutions shall certify that each 
proposal for research covered by this Sec.  __.103 has been reviewed 
and approved by the IRB. Such certification must be submitted as 
prescribed by the Federal department or agency component supporting the 
research. Under no condition shall research covered by this Sec.  
__.103 be initiated prior to receipt of the certification that the 
research has been reviewed and approved by the IRB.
    (e) For non-exempt research involving human subjects covered by 
this policy that takes place at an institution in which IRB oversight 
is conducted by an IRB that is not operated by the institution, the 
institution and the organization operating the IRB shall establish and 
follow procedures for documenting the institution's reliance on the IRB 
for oversight of the research and the responsibilities that each entity 
will undertake to ensure compliance with the requirements of this 
policy (e.g., in a written agreement between the institution and the 
IRB, or by implementation of an institution-wide policy directive 
providing the allocation of responsibilities between the institution 
and an IRB that is not affiliated with the institution).

(Approved by the Office of Management and Budget under Control Number.)


Sec.  __.104  Exempt research.

    (a) Unless otherwise required by department or agency heads, 
research activities in which the only involvement of human subjects 
will be in one or more of the categories in paragraphs (d) through (f) 
of this section are not subject to the requirements of this policy, 
other than those specified in the category.
    (b) Use of the exemption categories for research subject to the 
requirements of subparts B, C, and D. Application of the exemption 
categories to research subject to the requirements of 45 CFR part 46, 
subparts B, C, and D, is as follows:
    (1) Subpart B. Each of the exemptions at this Sec.  __.104 may be 
applied to research conducted under subpart B if the conditions of the 
exemption are met.
    (2) Subpart C. The exemptions at this Sec.  __.104 do not apply to 
research conducted under subpart C, except for research aimed at a 
broader population that consists mostly of non-prisoners but that 
incidentally includes some number of prisoners.
    (3) Subpart D. Only the exemptions at paragraphs (d)(1), (2), (4), 
(e)(2), and (f)(1) and (2) of this section may be applied to research 
conducted under subpart D if the conditions of the exemption are met.
    (c) Federal departments and agencies shall develop a decision tool 
to assist in exemption determinations. Unless otherwise required by 
law, exemption determinations shall be made by an individual who is 
knowledgeable about the exemption categories and who has access to 
sufficient information to make an informed and reasonable 
determination, or by the investigator or another individual at the 
institution who enters accurate information about the proposed research 
into the decision tool, which will provide a determination as to 
whether the study is exempt. If the decision tool is used, further 
assessment or evaluation of the exemption determination is not 
required. An institution or, when appropriate, the IRB, must maintain 
records of exemption determinations made for research subject to the 
requirements of this policy for which the institution or IRB exercises 
oversight responsibility. These records must include, at a minimum, the 
name of the research study, the name of the investigator, and the 
exemption category applied to the research study. Maintenance of the 
completed decision tool shall be considered to fulfill this 
recordkeeping requirement.
    (1) For studies exempted pursuant to paragraph (d)(2) of this 
section, the recordkeeping requirement will be deemed satisfied by the 
published list required at paragraph (d)(2)(i) of this section.
    (2) [Reserved].
    (d) The following categories of exempt human subjects research 
generally involve a low-risk intervention with human subjects, must be 
recorded as required in paragraph (c) of this section, and do not 
require application of standards for information and biospecimen 
protection provided in Sec.  __.105 or informed consent. Only paragraph 
(d)(2) of this section allows for the collection and use of 
biospecimens:
    (1) Research conducted in established or commonly accepted 
educational settings when it specifically involves normal educational 
practices. This includes most research on regular and special education 
instructional strategies, and research on the effectiveness of or the 
comparison among instructional techniques, curricula, or classroom 
management methods that are not likely to adversely impact students' 
opportunity to learn required educational content in that educational 
setting or the assessment of educators who provide instruction.
    (2) Research and demonstration projects that are conducted or 
supported by a Federal department or agency, or otherwise subject to 
the approval of department or agency heads, and that are designed to 
study, evaluate, or otherwise examine public benefit or service 
programs, including procedures for obtaining benefits or services under 
those programs, possible changes in or alternatives to those programs 
or procedures, or possible changes in methods or levels of payment for 
benefits or services under those programs.
    (i) Each Federal department or agency conducting or supporting the 
research and demonstration projects must establish, on a publicly 
accessible federal Web site or in such other manner as the department 
or agency head may prescribe, a list of the research and demonstration 
projects that the Federal department or agency conducts or supports 
under this provision. The research or demonstration project must be 
published on this list prior to or upon commencement of the research.
    (ii) [Reserved]
    (3)(i) Research involving benign interventions in conjunction with 
the collection of data from an adult subject through verbal or written 
responses (including data entry) or video recording if the subject 
prospectively agrees to the intervention and data collection and at 
least one of the following criteria is met:
    (A) The information obtained is recorded in such a manner that 
human subjects cannot be identified directly or through identifiers 
linked to the subjects; or
    (B) Any disclosure of the human subjects' responses outside the 
research would not reasonably place the subjects at risk of criminal or 
civil liability or be damaging to the subjects' financial standing, 
employability, educational advancement, or reputation.
    (ii) For the purpose of this provision, benign interventions are 
brief in duration, harmless, painless, not physically invasive, not 
likely to have a significant adverse lasting impact on the subjects, 
and the investigator has no reason to think the subjects will find the 
interventions offensive or embarrassing. If these criteria are met, 
such benign interventions might include research activities in which a 
subject is asked to read materials, review pictures or videos, play 
online games, solve puzzles, or perform cognitive tasks.

[[Page 54049]]

    (iii) If the research involves deceiving the subjects regarding the 
nature or purposes of the research, this exemption is not applicable 
unless the subject authorizes the deception as described in paragraph 
(d)(3)(iv) of this section.
    (iv) For the purpose of this provision, authorized deception is 
prospective agreement by the subject to participate in research where 
the subject is informed that he or she will be unaware of or misled 
regarding the nature or purposes of the research.
    (4) Taste and food quality evaluation and consumer acceptance 
studies
    (i) If wholesome foods without additives are consumed, or
    (ii) If a food is consumed that contains a food ingredient at or 
below the level and for a use found to be safe, or agricultural 
chemical or environmental contaminant at or below the level found to be 
safe, by the Food and Drug Administration or approved by the 
Environmental Protection Agency or the Food Safety and Inspection 
Service of the U.S. Department of Agriculture.
    (e) The following categories of exempt human subjects research 
allow for the collection of sensitive information about human subjects, 
must not involve biospecimens, must be recorded as required in 
paragraph (c) of this section, and require application of standards for 
information and biospecimen protection provided in Sec.  __.105:
    (1) Research, not including interventions, involving the use of 
educational tests (cognitive, diagnostic, aptitude, achievement), 
survey procedures, interview procedures, or observation of public 
behavior (including visual or auditory recording), if the information 
obtained is recorded in such a manner that human subjects can be 
identified directly or through identifiers linked to the subjects.
    (2) Secondary research use of identifiable private information that 
has been or will be acquired for non-research purposes, if the 
following criteria are met:
    (i) Prior notice has been given to the individuals to whom the 
identifiable private information pertains that such information may be 
used in research; and
    (ii) The identifiable private information is used only for purposes 
of the specific research for which the investigator or recipient entity 
requested access to the information.
    (f) The following categories of exempt human subjects research 
involve biospecimens or identifiable private information, must be 
recorded as required in paragraph (c) of this section, require 
application of standards for information and biospecimen protection as 
described in Sec.  __.105, and require informed consent and limited IRB 
review to the extent described in each category or otherwise required 
by law:
    (1)(i) Storage or maintenance for secondary research use of 
biospecimens or identifiable private information that have been or will 
be acquired for research studies other than for the proposed research 
study, or for non-research purposes, if the following criteria are met:
    (A) Written consent for the storage, maintenance, and secondary 
research use of the information or biospecimens is obtained in 
accordance with Sec.  __.116(c) and (d)(2), and the template published 
by the Secretary of HHS in accordance with Sec.  __.116(d)(1) must be 
used. Oral consent, if obtained during the original data collection and 
in accordance with Sec.  __.116(c) and (d)(3), would be satisfactory 
for the research use of identifiable private information initially 
acquired in accordance with activities excluded from this policy under 
Sec.  __.101(b)(2)(i) or exempt from this policy in accordance with 
Sec.  __.104(d)(3) or (4), or Sec.  __.104(e)(1);
    (B) The reviewing IRB makes the determinations required by Sec.  
__.111(a)(9).
    (ii) [Reserved.]
    (2)(i) Research involving the use of biospecimens or identifiable 
private information that have been stored or maintained for secondary 
research use, if consent for the storage, maintenance, and secondary 
research use of the information and biospecimens was obtained as 
detailed in paragraph (f)(1)(i)(A) of this section.
    (ii) If the investigator anticipates that individual research 
results will be provided to a research subject, the research may not be 
exempted under this provision and must be reviewed by the IRB and 
informed consent for the research must be obtained to the extent 
required by Sec.  __.116(a) and (b).


Sec.  __.105  Protection of biospecimens and identifiable private 
information.

    (a) In General. Institutions and investigators conducting research 
that is subject to this policy, or that is exempt from this policy 
under Sec.  __.104(e) or (f), involving the collection, storage, or use 
of biospecimens or identifiable private information, shall implement 
and maintain reasonable and appropriate safeguards as specified in 
paragraph (b) of this section to protect biospecimens or identifiable 
private information that they collect, obtain, receive, maintain, or 
transmit for research. The safeguards shall reasonably protect against 
anticipated threats or hazards to the security or integrity of the 
information or biospecimens, as well as reasonably protect the 
information and biospecimens from any intentional or unintentional use, 
release, or disclosure that is in violation of paragraph (c) of this 
section. IRB review of the safeguards required by this section is not 
required, except to the extent required by Sec.  __.104(f)(1).
    (b) Safeguards requirements. The Secretary of HHS shall establish 
and publish for public comment a list of specific measures that the 
institution or investigator may implement that will be deemed to 
satisfy the requirement for reasonable and appropriate safeguards. The 
list will be evaluated as needed, but at least every 8 years, and 
amended, as appropriate, after consultation with other Federal 
departments and agencies. The institutions and investigators identified 
in paragraph (a) of this section shall implement paragraph (a) of this 
section by choosing either to apply the safeguards identified by the 
Secretary as necessary to protect the security or integrity of and 
limit disclosure of biospecimens and electronic and non-electronic 
identifiable private information, or to apply safeguards that meet the 
standards in 45 CFR 164.308, 164.310, 164.312, and 45 CFR 164.530(c). 
For Federal departments and agencies that conduct research activities 
that is or will be maintained on information technology that is subject 
to and in compliance with section 208(b) of the E-Government Act of 
2002, 44 U.S.C. 3501 note, if all of the information collected, used, 
or generated as part of the activity will be maintained in systems of 
records subject to the Privacy Act of 1974, 5 U.S.C. 552a, and the 
research will involve a collection of information subject to the 
Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq., these research 
activities automatically will be considered in compliance with the 
Secretary's reasonable and appropriate safeguards standards, unless or 
until any additional safeguards are identified by the Secretary of HHS.
    (c) Limitations on use, release, and disclosure. Unless otherwise 
required by law, institutions and investigators shall use or release 
biospecimens or use or disclose identifiable private information 
collected or maintained for research only:
    (1) For human subjects research regulated by this policy;
    (2) For public health purposes;
    (3) For any lawful purpose with the consent of the subject; or

[[Page 54050]]

    (4) For other research purposes if the institution or investigator 
has obtained adequate assurances from the recipient that
    (i) The recipient will implement and maintain the level of 
safeguards required by paragraph (b) of this section;
    (ii) Except for research that qualifies for exclusion under Sec.  
__.101(b) or exemption under Sec.  __.104 the releasing or disclosing 
institution or investigator shall obtain documentation from the 
recipient that the research has been approved under Sec.  __.111 to the 
extent required before releasing biospecimens or disclosing 
identifiable private information; and
    (iii) The recipient shall not further release the biospecimens or 
disclose identifiable private information except for human subjects 
research regulated by this policy, or for other purposes permitted by 
this paragraph. For the purposes of this requirement, an institution or 
investigator shall obtain adequate assurances through the use of a 
written agreement with the recipient that the recipient will abide by 
these conditions.
    (d) The provisions of this section do not amend or repeal, and 
shall not be construed to amend or repeal, the requirements of 45 CFR 
parts 160 and 164 for the institutions or investigators, including 
Federal departments or agencies, to which these regulations are 
applicable pursuant to 45 CFR 160.102.


Sec.  __.106  [Reserved]


Sec.  __.107  IRB membership.

    (a) Each IRB shall have at least five members, with varying 
backgrounds to promote complete and adequate review of research 
activities commonly conducted by the institution. The IRB shall be 
sufficiently qualified through the experience and expertise of its 
members (professional competence), and the diversity of its members, 
including race, gender, and cultural backgrounds and sensitivity to 
such issues as community attitudes, to promote respect for its advice 
and counsel in safeguarding the rights and welfare of human subjects. 
The IRB shall be able to ascertain the acceptability of proposed 
research in terms of institutional commitments (including policies and 
resources) and regulations, applicable law, and standards of 
professional conduct and practice. The IRB shall therefore include 
persons knowledgeable in these areas. If an IRB regularly reviews 
research that involves a category of subjects that is vulnerable to 
coercion or undue influence, such as children, prisoners, pregnant 
women, physically or mentally disabled persons, or economically or 
educationally disadvantaged persons, consideration shall be given to 
the inclusion of one or more individuals who are knowledgeable about 
and experienced in working with these categories of subjects.
    (b) Each IRB shall include at least one member whose primary 
concerns are in scientific areas and at least one member whose primary 
concerns are in nonscientific areas.
    (c) Each IRB shall include at least one member who is not otherwise 
affiliated with the institution and who is not part of the immediate 
family of a person who is affiliated with the institution.
    (d) No IRB may have a member participate in the IRB's initial or 
continuing review of any project in which the member has a conflicting 
interest, except to provide information requested by the IRB.
    (e) An IRB may, in its discretion, invite individuals with 
competence in special areas to assist in the review of issues that 
require expertise beyond or in addition to that available on the IRB. 
These individuals may not vote with the IRB.


Sec.  __.108  IRB functions and operations.

    (a) In order to fulfill the requirements of this policy each IRB 
shall:
    (1) Have access to meeting space and sufficient staff to support 
the IRB's review and recordkeeping duties;
    (2) Prepare and maintain a current list of the IRB members 
identified by name; earned degrees; representative capacity; 
indications of experience such as board certifications or licenses 
sufficient to describe each member's chief anticipated contributions to 
IRB deliberations; and any employment or other relationship between 
each member and the institution, for example, full-time employee, part-
time employee, member of governing panel or board, stockholder, paid or 
unpaid consultant;
    (3) Establish and follow written procedures for:
    (i) Conducting its initial and continuing review of research and 
for reporting its findings and actions to the investigator and the 
institution;
    (ii) Determining which projects require review more often than 
annually and which projects need verification from sources other than 
the investigators that no material changes have occurred since previous 
IRB review; and
    (iii) Ensuring prompt reporting to the IRB of proposed changes in a 
research activity, and for ensuring that such changes in approved 
research, during the period for which IRB approval has already been 
given, may not be initiated without IRB review and approval except when 
necessary to eliminate apparent immediate hazards to the subject.
    (4) Establish and follow written procedures for ensuring prompt 
reporting to the IRB; appropriate institutional officials; the 
department or agency head; and the Office for Human Research 
Protections, HHS, or any successor office, or the equivalent office 
within the appropriate Federal department or agency of
    (i) Any unanticipated problems involving risks to subjects or 
others or any serious or continuing noncompliance with this policy or 
the requirements or determinations of the IRB; and
    (ii) Any suspension or termination of IRB approval.
    (b) Except when an expedited review procedure is used (as described 
in Sec.  __.110), an IRB must review proposed research at convened 
meetings at which a majority of the members of the IRB are present, 
including at least one member whose primary concerns are in 
nonscientific areas. In order for the research to be approved, it shall 
receive the approval of a majority of those members present at the 
meeting.


Sec.  __.109  IRB review of research.

    (a) An IRB shall review and have authority to approve, require 
modifications in (to secure approval), or disapprove all research 
activities covered by this policy that do not qualify for exemption 
pursuant to Sec.  __.104(d), (e), or (f)(2).
    (b) An IRB shall require that information given to subjects as part 
of informed consent is in accordance with Sec.  __.116. The IRB may 
require that information, in addition to that specifically mentioned in 
Sec.  __.116, be given to the subjects when in the IRB's judgment the 
information would meaningfully add to the protection of the rights and 
welfare of subjects.
    (c) An IRB shall require documentation of informed consent or may 
waive documentation in accordance with Sec.  __.117.
    (d) An IRB shall notify investigators and the institution in 
writing of its decision to approve or disapprove the proposed research 
activity, or of modifications required to secure IRB approval of the 
research activity. If the IRB decides to disapprove a research 
activity, it shall include in its written notification a statement of 
the reasons for its decision and give the investigator an opportunity 
to respond in person or in writing.
    (e) An IRB shall conduct continuing review of research requiring 
review by

[[Page 54051]]

the convened IRB at intervals appropriate to the degree of risk, not 
less than once per year, except as described in Sec.  __.109(f).
    (f)(1) Unless an IRB determines otherwise, continuing review of 
research is not required in the following circumstances:
    (i) Research eligible for expedited review in accordance with Sec.  
__.110;
    (ii) Research that has progressed to the point that it involves 
only one or both of the following, which are part of the IRB-approved 
study:
    (A) Data analysis, including analysis of identifiable private 
information, or
    (B) Accessing follow-up clinical data from procedures that subjects 
would undergo as part of standard care for their medical condition; or
    (iii) Research reviewed by the IRB in accordance with the limited 
IRB review procedure described in Sec.  __.111(a)(9).
    (2) The IRB must receive confirmation on an annual basis that the 
research is still ongoing and that no changes have been made to the 
research that would require the IRB to conduct continuing review of the 
research.
    (g) An IRB shall have authority to observe or have a third party 
observe the consent process and the research.


(Approved by the Office of Management and Budget under Control Number.)


Sec.  __.110  Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in approved 
research.

    (a) The Secretary of HHS, has established, and published as a 
Notice in the Federal Register, a list of categories of research that 
may be reviewed by the IRB through an expedited review procedure. The 
Secretary will evaluate the list at least every 8 years and amend it, 
as appropriate, after consultation with other federal departments and 
agencies and after publication in the Federal Register for public 
comment. A copy of the list is available from the Office for Human 
Research Protections, HHS, or any successor office.
    (b)(1) An IRB may use the expedited review procedure to review the 
following:
    (i) Some or all of the research appearing on the list, unless the 
reviewer determines that the study involves more than minimal risk;
    (ii) Minor changes in previously approved research during the 
period for which approval is authorized; or
    (iii) Research that is being reviewed to determine whether it 
qualifies for exemption in accordance with Sec.  __.104(f)(1) in order 
to determine that the requirements of Sec.  __.111(a)(9) are satisfied.
    (2) Under an expedited review procedure, the review may be carried 
out by the IRB chairperson or by one or more experienced reviewers 
designated by the chairperson from among members of the IRB. In 
reviewing the research, the reviewers may exercise all of the 
authorities of the IRB except that the reviewers may not disapprove the 
research. A research activity may be disapproved only after review in 
accordance with the non-expedited procedure set forth in Sec.  
__.108(b).
    (c) Each IRB that uses an expedited review procedure shall adopt a 
method for keeping all members advised of research proposals that have 
been approved under the procedure.
    (d) The department or agency head may restrict, suspend, terminate, 
or choose not to authorize an institution's or IRB's use of the 
expedited review procedure.


Sec.  __.111  Criteria for IRB approval of research.

    (a) In order to approve research covered by this policy the IRB 
shall determine that all of the following requirements are satisfied:
    (1) Risks to subjects are minimized:
    (i) By using procedures that are consistent with sound research 
design and that do not unnecessarily expose subjects to risk, and
    (ii) Whenever appropriate, by using procedures already being 
performed on the subjects for diagnostic or treatment purposes.
    (2) Risks to subjects are reasonable in relation to anticipated 
benefits, if any, to subjects, and the importance of the knowledge that 
may reasonably be expected to result. In evaluating risks and benefits, 
the IRB should consider only those risks and benefits that may result 
from the research (as distinguished from risks and benefits of 
therapies subjects would receive even if not participating in the 
research). The IRB should not consider possible long-range effects of 
applying knowledge gained in the research (e.g., the possible effects 
of the research on public policy) as among those research risks that 
fall within the purview of its responsibility.
    (3) Selection of subjects is equitable. In making this assessment 
the IRB should take into account the purposes of the research and the 
setting in which the research will be conducted and should be 
particularly cognizant of the special problems of research that 
involves a category of subjects who are vulnerable to coercion or undue 
influence, such as children, prisoners, pregnant women, physically or 
mentally disabled persons, or economically or educationally 
disadvantaged persons.
    (4) Informed consent will be sought from each prospective subject 
or the subject's legally authorized representative, in accordance with, 
and to the extent required by, Sec.  __.116.
    (5) Informed consent will be appropriately documented, in 
accordance with, and to the extent required by, Sec.  __.117.
    (6) When appropriate, the research plan makes adequate provision 
for monitoring the data collected to ensure the safety of subjects.
    (7) When appropriate, there are adequate provisions to protect the 
privacy of subjects and to maintain the confidentiality of data, in 
addition to the requirements in Sec.  __.105, if the IRB determines 
that the standards for information and biospecimen protection in Sec.  
__.105 are not sufficient to protect the privacy of subjects and the 
confidentiality of data.
    (8) If the investigator proposes a research plan for returning 
clinically relevant results to subjects, that the plan is appropriate.
    (9) For purposes of conducting the limited IRB review as required 
by Sec.  __.104(f)(1), the IRB need not make the determinations at 
paragraphs (a)(1) through (8) of this section, and shall determine that 
the following requirements are satisfied:
    (i) The procedures for obtaining broad consent for storage, 
maintenance, and secondary research use of biospecimens or identifiable 
private information will be conducted in accordance with the 
requirements of the first paragraph in Sec.  __.116.
    (ii) If there will be a change for research purposes in the way the 
biospecimens or information are stored or maintained, that the privacy 
and information protection standards at Sec.  __.105 are satisfied for 
the creation of any related storage database or repository.
    (b) When some or all of the subjects are likely to be vulnerable to 
coercion or undue influence, such as children, prisoners, pregnant 
women, physically or mentally disabled persons, or economically or 
educationally disadvantaged persons, additional safeguards have been 
included in the study to protect the rights and welfare of these 
subjects.


Sec.  __.112  Review by institution.

    Research covered by this policy that has been approved by an IRB 
may be subject to further appropriate review and approval or 
disapproval by officials of the institution. However, those

[[Page 54052]]

officials may not approve the research if it has not been approved by 
an IRB.


Sec.  __.113  Suspension or termination of IRB approval of research.

    An IRB shall have authority to suspend or terminate approval of 
research that is not being conducted in accordance with the IRB's 
requirements or that has been associated with unexpected serious harm 
to subjects. Any suspension or termination of approval shall include a 
statement of the reasons for the IRB's action and shall be reported 
promptly to the investigator, appropriate institutional officials, and 
the department or agency head.


(Approved by the Office of Management and Budget under Control Number.)


Sec.  __.114  Cooperative research.

    (a) Cooperative research projects are those projects covered by 
this policy that involve more than one institution. In the conduct of 
cooperative research projects, each institution is responsible for 
safeguarding the rights and welfare of human subjects and for complying 
with this policy.
    (b)(1) Any institution located in the United States that is engaged 
in cooperative research must rely upon approval by a single IRB for 
that portion of the research that is conducted in the United States. 
The reviewing IRB will be selected by the Federal department or agency 
supporting or conducting the research or, if there is no funding 
agency, by the lead institution conducting the research.
    (2) The following research is not subject to the requirements of 
this provision:
    (i) Cooperative research for which more than single IRB review is 
required by law; or
    (ii) Research for which the Federal department or agency supporting 
or conducting the research determines and documents that the use of a 
single IRB is not appropriate for the particular study.
    (c) For research not subject to paragraph (b) of this section, an 
institution participating in a cooperative project may enter into a 
joint review arrangement, rely on the review of another IRB, or make 
similar arrangements for avoiding duplication of effort.


Sec.  __.115  IRB records.

    (a) An institution, or when appropriate an IRB, shall prepare and 
maintain adequate documentation of IRB activities, including the 
following:
    (1) Copies of all research proposals reviewed, scientific 
evaluations, if any, that accompany the proposals, approved sample 
consent forms, progress reports submitted by investigators, and reports 
of injuries to subjects.
    (2) Minutes of IRB meetings, which shall be in sufficient detail to 
show attendance at the meetings; actions taken by the IRB; the vote on 
these actions including the number of members voting for, against, and 
abstaining; the basis for requiring changes in or disapproving 
research; and a written summary of the discussion of controverted 
issues and their resolution.
    (3) Records of continuing review activities, including the 
rationale for conducting continuing review of research that has 
progressed to the point that it involves only one or both of the 
following:
    (i) Data analysis, including analysis of identifiable private 
information, or
    (ii) Accessing follow-up clinical data from procedures that 
subjects would undergo as part of standard care for their medical 
condition.
    (4) Copies of all correspondence between the IRB and the 
investigators.
    (5) A list of IRB members in the same detail as described in Sec.  
__.108(a)(2).
    (6) Written procedures for the IRB in the same detail as described 
in Sec.  __.108(a)(3) and (4).
    (7) Statements of significant new findings provided to subjects, as 
required by Sec.  __.116(b)(5).
    (8) The rationale for requiring continuing review for research that 
otherwise would not require continuing review as described in Sec.  
__.109(f)(1).
    (9) The rationale for an expedited reviewer's determination that 
research appearing on the expedited review list described in Sec.  
__.110(b)(1)(i) is more than minimal risk.
    (10) The written agreement between an institution and an 
organization operating an IRB specifying the responsibilities that each 
entity will undertake to ensure compliance with the requirements of 
this policy, as described in Sec.  __.103(e).
    (11) Records relating to exemption determinations, as described in 
Sec.  __.104(c).
    (b) The records required by this policy shall be retained for at 
least 3 years, and records relating to research that is conducted shall 
be retained for at least 3 years after completion of the research. The 
institution or IRB may maintain the records in printed form, or 
electronically. All records shall be accessible for inspection and 
copying by authorized representatives of the Federal department or 
agency at reasonable times and in a reasonable manner.
    (c) The institution or IRB retaining the records shall safeguard 
identifiable private information contained within these records in 
compliance with Sec.  __.105.


(Approved by the Office of Management and Budget under Control Number.)


Sec.  __.116  General requirements for informed consent.

    Except as provided elsewhere in this policy, no investigator may 
involve a human subject in research covered by this policy unless the 
investigator has obtained the legally effective informed consent of the 
subject or the subject's legally authorized representative. An 
investigator shall seek such consent only under circumstances that 
provide the prospective subject or the representative sufficient 
opportunity to consider whether or not to participate and that minimize 
the possibility of coercion or undue influence. The information that is 
given to the subject or the representative shall be in language 
understandable to the subject or the representative. The prospective 
subject or the representative must be provided with the information 
that a reasonable person would want to have in order to make an 
informed decision about whether to participate, and an opportunity to 
discuss that information. The information must be presented in 
sufficient detail relating to the specific research, and must be 
organized and presented in a way that does not merely provide lists of 
isolated facts, but rather facilitates the prospective subject's or 
representative's understanding of the reasons why one might or might 
not want to participate. In obtaining informed consent, the 
investigator must present first the information required by this 
section, before providing other information, if any, to the subject or 
the representative. Any informed consent form must include only the 
requirements of informed consent under this section, and appendices 
that include any other information provided to the subject or the 
representative. If an authorization required by 45 CFR parts 160 and 
164 is combined with a consent form, the authorization elements 
required by 45 CFR 164.508 must be included in the consent form and not 
the appendices. No informed consent, whether oral or written, may 
include any exculpatory language through which the subject or the 
representative is made to waive or appear to waive any of the subject's 
legal rights, or releases or appears to release the investigator, the 
sponsor, the institution, or its agents from liability for negligence.

[[Page 54053]]

    (a) Basic elements of informed consent. Except as provided in 
paragraph (c), (e), or (f) of this section, in seeking informed consent 
the following information shall be provided to each subject or the 
representative:
    (1) A statement that the study involves research, an explanation of 
the purposes of the research and the expected duration of the subject's 
participation, a description of the procedures to be followed, and 
identification of any procedures that are experimental;
    (2) A description of any reasonably foreseeable risks or 
discomforts to the subject;
    (3) A description of any benefits to the subject or to others that 
may reasonably be expected from the research;
    (4) A disclosure of appropriate alternative procedures or courses 
of treatment, if any, that might be advantageous to the subject;
    (5) A statement describing the extent, if any, to which 
confidentiality of records identifying the subject will be maintained;
    (6) For research involving more than minimal risk, an explanation 
as to whether any compensation and an explanation as to whether any 
medical treatments are available if injury occurs and, if so, what they 
consist of, or where further information may be obtained;
    (7) An explanation of whom to contact for answers to pertinent 
questions about the research and research subjects' rights, and whom to 
contact in the event of a research-related injury to the subject;
    (8) A statement that participation is voluntary, refusal to 
participate will involve no penalty or loss of benefits to which the 
subject is otherwise entitled, and the subject may discontinue 
participation at any time without penalty or loss of benefits to which 
the subject is otherwise entitled; and
    (9) One of the following statements about any research that 
involves the collection of identifiable private information:
    (i) A statement that identifiers might be removed from the data and 
the data that is not identifiable could be used for future research 
studies or distributed to another investigator for future research 
studies without additional informed consent from the subject or the 
representative, if this might be a possibility; or
    (ii) A statement that the subject's data collected as part of the 
research, from which identifiers are removed, will not be used or 
distributed for future research studies.
    (b) Additional elements of informed consent. Except as provided in 
paragraphs (c), (e), or (f) of this section, when appropriate, one or 
more of the following elements of information shall also be provided to 
each subject or the representative:
    (1) A statement that the particular treatment or procedure may 
involve risks to the subject (or to the embryo or fetus, if the subject 
is or may become pregnant) that are currently unforeseeable;
    (2) Anticipated circumstances under which the subject's 
participation may be terminated by the investigator without regard to 
the subject's or the representative's consent;
    (3) Any additional costs to the subject that may result from 
participation in the research;
    (4) The consequences of a subject's decision to withdraw from the 
research and procedures for orderly termination of participation by the 
subject;
    (5) A statement that significant new findings developed during the 
course of the research that may relate to the subject's willingness to 
continue participation will be provided to the subject;
    (6) The approximate number of subjects involved in the study;
    (7) A statement that the subject's biospecimens may be used for 
commercial profit and whether the subject will or will not share in 
this commercial profit;
    (8) A statement regarding whether clinically relevant research 
results, including individual research results, will be disclosed to 
subjects, and if so, under what conditions; and
    (9) An option for the subject or the representative to consent, or 
refuse to consent, to investigators re-contacting the subject to seek 
additional information or biospecimens or to discuss participation in 
another research study.
    (c)(1) Elements of informed consent for broad consent to the 
storage, maintenance, and secondary research use of biospecimens or 
identifiable private information. If the subject or the representative 
will be asked to provide broad consent to the storage or maintenance of 
biospecimens or identifiable private information, collected for either 
research studies other than the proposed research or non-research 
purposes, and the secondary research use of this stored material, the 
information required in paragraphs (a)(2), (3), (5), and (7) and, if 
applicable, (b)(7) through (9) of this section, shall be provided to 
each subject, with the following additional information:
    (i) A general description of the types of research that may be 
conducted with information and biospecimens and the information that is 
expected to be generated from the research, the types of information or 
biospecimens that might be used in research, and the types of 
institutions that might conduct research with the biospecimens or 
information;
    (ii) A description of the scope of the informed consent must be 
provided, including:
    (A) A clear description of the types of biospecimens or information 
that were or will be collected and the period of time during which 
biospecimen or information collection will occur. This may include all 
biospecimens and information from the subject's medical record or other 
records existing at the institution at the time informed consent is 
sought; and
    (B) For purposes of paragraph (c)(1)(ii)(A) of this section, the 
period of time during which biospecimen or information collection will 
occur cannot exceed 10 years from the date of consent. For research 
involving children as subjects, that time period cannot exceed 10 years 
after parental permission is obtained or until the child reaches the 
legal age for consent to the treatments or procedures involved in the 
research, whichever time period is shorter. The time limitations 
described do not apply to biospecimens or information that initially 
will be collected for research purposes.
    (iii) A description of the period of time during which an 
investigator can continue to conduct research using the subject's 
biospecimens and information described in paragraph (c)(1)(ii)(A) of 
this section (e.g., a certain number of years, or indefinitely);
    (iv) A statement that participation is voluntary, refusal to 
participate will involve no penalty or loss of benefits to which the 
subject is otherwise entitled, and that the subject may withdraw 
consent, if feasible, for research use or distribution of the subject's 
information or biospecimens at any time without penalty or loss of 
benefits to which the subject is otherwise entitled, and information 
about whom to contact in order for the subject to withdraw consent. The 
statement must make clear that information or biospecimens that already 
have been distributed for research use may not be retrieved;
    (v) If applicable, a statement notifying the subject or the 
representative that the subject or the representative will not be 
informed of the details of any specific research studies that might be 
conducted, including the purposes of the research, that will use the 
subject's information and biospecimens;
    (vi) If applicable, a statement notifying the subject or the

[[Page 54054]]

representative of the expectation that the subject's information and 
biospecimens are likely to be used by multiple investigators and 
institutions and shared broadly for many types of research studies in 
the future, and this information and the biospecimens might be 
identifiable when shared;
    (vii)The names of the institution or set of institutions at which 
the subject's biospecimens or information were or will be collected, to 
the extent possible (in recognition that institutions might change 
names or cease to exist); and
    (viii) If relevant, an option for an adult subject or the 
representative to consent, or refuse to consent, to the inclusion of 
the subject's data, with removal of the identifiers listed in 45 CFR 
164.514(b)(2)(i)(A) through (Q), in a database that is publicly and 
openly accessible to anyone. This option must be prominently noted, and 
must include a description of risks of public access to the data.
    (2) [Reserved]
    (d)(1) The Secretary of HHS will establish, and publish in the 
Federal Register for public comment, templates for consent that will 
contain all of the required elements of informed consent under 
paragraph (c) of this section. IRB review of the broad secondary use 
informed consent form obtained in accordance with paragraph (c) of this 
section is required unless the consent is obtained using only this 
template, without any changes.
    (2) If Sec.  __.104(f)(1) requires written consent, the consent for 
research use of biospecimens or identifiable private information must 
be documented by the use of a written consent form signed by the 
subject or the representative. The template for consent for research 
use established by the Secretary may serve as the written consent form. 
A copy shall be given to the person signing the form.
    (3) If Sec.  __.104(f)(1) allows for oral consent, a subject's or 
the representative's oral consent for research use of identifiable 
private information must be documented such that the consent is 
associated with the subject's identifiable private information. If this 
requirement is met through the use of written documentation, the 
subject or the representative is not required to sign the 
documentation.
    (4) If the subject or the representative declines to consent to the 
research use of biospecimens or identifiable private information, this 
must be documented appropriately.
    (e)(1) Waiver or alteration of consent in research involving public 
benefit and service programs conducted by or subject to the approval of 
state or local officials. An IRB may approve a consent procedure that 
does not include, or that alters, some or all of the elements of 
informed consent set forth above, or waive the above requirement to 
obtain informed consent, provided the IRB finds and documents that:
    (i) The research or demonstration project is to be conducted by or 
subject to the approval of state or local government officials and is 
designed to study, evaluate, or otherwise examine:
    (A) Public benefit or service programs;
    (B) Procedures for obtaining benefits or services under those 
programs;
    (C) Possible changes in or alternatives to those programs or 
procedures; or
    (D) Possible changes in methods or levels of payment for benefits 
or services under those programs; and
    (ii) The research could not practicably be carried out without the 
waiver or alteration.
    (2) Additional criteria for waiver or alteration of consent for 
biospecimens. For research involving the use of biospecimens, an IRB 
may approve a consent procedure that does not include, or that alters, 
some or all of the elements of informed consent set forth above, or 
waive the above requirements to obtain informed consent, provided the 
IRB finds and documents the criteria in paragraph (e)(1) of this 
section, and the following additional criteria:
    (i) There are compelling scientific reasons to conduct the 
research; and
    (ii) The research could not be conducted with other biospecimens 
for which informed consent was obtained or could be obtained.
    (3) If an individual was asked to consent to the storage or 
maintenance for secondary research use of biospecimens or identifiable 
private information in accordance with the requirements of this section 
at paragraph (c) of this section, and refused to consent, an IRB cannot 
waive consent for either the storage or maintenance for secondary 
research use, or for the secondary research use, of those biospecimens 
or information.
    (f)(1) Waiver or alteration of consent. An IRB may approve a 
consent procedure that does not include, or that alters, some or all of 
the elements of informed consent set forth above, or waive the above 
requirements to obtain informed consent, provided the IRB finds and 
documents that:
    (i) The research involves no more than minimal risk to the 
subjects;
    (ii) The research could not practicably be carried out without the 
requested waiver or alteration;
    (iii) If the research involves accessing or using identifiable 
biospecimens or identifiable information, the research could not 
practicably be carried out without accessing or using identifiers;
    (iv) The waiver or alteration will not adversely affect the rights 
and welfare of the subjects; and
    (v) Whenever appropriate, the subjects will be provided with 
additional pertinent information after participation.
    (2) Additional criteria for waiver or alteration of consent for 
research involving biospecimens. For research involving the use of 
biospecimens, an IRB may approve a consent procedure that does not 
include, or that alters, some or all of the elements of informed 
consent set forth above, or waive the above requirements to obtain 
informed consent, provided the IRB finds and documents the criteria in 
paragraph (f)(1) of this section, and the following additional 
criteria:
    (i) There are compelling scientific reasons for the research use of 
the biospecimens; and
    (ii) The research could not be conducted with other biospecimens 
for which informed consent was obtained or could be obtained.
    (3) If an individual was asked to consent to the storage or 
maintenance for secondary research use of biospecimens or identifiable 
private information, in accordance with the requirements of paragraph 
(c) of this section, and refused to consent, an IRB cannot waive 
consent for either the storage or maintenance for secondary research 
use, or for the secondary research use, of those biospecimens or 
information.
    (g) An IRB may approve a research proposal in which investigators 
obtain, through oral or written communication or by accessing records, 
identifiable private information without individuals' informed consent 
for the purpose of screening, recruiting, or determining the 
eligibility of prospective human subjects of research, provided that 
the research proposal includes an assurance that the investigator will 
implement standards for protecting the information obtained, in 
accordance with and to the extent required by Sec.  __.105.
    (h)(1) A copy of the final version of the informed consent form for 
each clinical trial conducted or supported by a Federal department or 
agency must be posted by the awardee or the Federal department or 
agency component conducting the trial on a publicly available federal 
Web site that will be established as a repository for such informed 
consent forms . The informed consent form must be posted in such form 
and manner as the department or agency head may prescribe, which will

[[Page 54055]]

include at a minimum posting, in addition to the informed consent form, 
the name of the clinical trial and information about whom to contact 
for additional details about the clinical trial.
    (2) The informed consent form must be posted on the federal Web 
site within 60 days after the trial is closed to recruitment.
    (i) The informed consent requirements in this policy are not 
intended to preempt any applicable Federal, state, or local laws that 
require additional information to be disclosed in order for informed 
consent to be legally effective.
    (j) Nothing in this policy is intended to limit the authority of a 
physician to provide emergency medical care, to the extent the 
physician is permitted to do so under applicable federal, state, or 
local law.


(Approved by the Office of Management and Budget under Control Number.)


Sec.  __.117  Documentation of informed consent.

    (a) Except as provided in paragraph (c) of this section, and except 
for research for which consent is obtained in accordance with Sec.  
__.116(c), informed consent shall be documented by the use of a written 
informed consent form approved by the IRB and signed by the subject or 
the subject's legally authorized representative. A copy shall be given 
to the person signing the informed consent form.
    (b) Except as provided in paragraph (c) of this section, the 
informed consent form may be either of the following:
    (1) A written informed consent form that includes a form containing 
only the information required by Sec.  __.116, and appendices that 
include any other information. The investigator shall give either the 
subject or the subject's legally authorized representative adequate 
opportunity to read the informed consent form before it is signed; 
alternatively, this form may be read to the subject or the subject's 
legally authorized representative.
    (2) A short form written informed consent form stating that the 
elements of informed consent required by Sec.  __.116 have been 
presented orally to the subject or the subject's legally authorized 
representative, and that the information required by Sec.  __.116 was 
presented first to the subject, before other information, if any, was 
provided. The IRB shall approve a written summary of what is to be said 
to the subject or the representative. When this method is used, there 
shall be a witness to the oral presentation. Only the short form itself 
is to be signed by the subject or the representative. However, the 
witness shall sign both the short form and a copy of the summary, and 
the person actually obtaining consent shall sign a copy of the summary. 
A copy of the summary shall be given to the subject or the 
representative, in addition to a copy of the short form.
    (c)(1) An IRB may waive the requirement for the investigator to 
obtain a signed informed consent form for some or all subjects if it 
finds any of the following:
    (i) That the only record linking the subject and the research would 
be the informed consent form and the principal risk would be potential 
harm resulting from a breach of confidentiality. Each subject will be 
asked whether the subject wants documentation linking the subject with 
the research, and the subject's wishes will govern;
    (ii) That the research presents no more than minimal risk of harm 
to subjects and involves no procedures for which written consent is 
normally required outside of the research context; or
    (iii) If the subjects are members of a distinct cultural group or 
community in which signing forms is not the norm, that the research 
presents no more than minimal risk of harm to subjects and provided 
there is an appropriate alternative mechanism for documenting that 
informed consent was obtained. Documentation must include a description 
as to why signing forms is not the norm for the distinct cultural group 
or community.
    (2) In cases in which the documentation requirement is waived, the 
IRB may require the investigator to provide subjects with a written 
statement regarding the research.
    (3) This waiver does not apply to research for which consent is 
required to be documented in accordance with Sec.  __.116(d)(2), (3), 
or (4).
    (4) Documentation of informed consent may not be waived under 
paragraphs (c)(1)(i) or (iii) of this section for research subject to 
regulation by the Food and Drug Administration unless otherwise 
authorized by 21 CFR 56.109(c)(1).


(Approved by the Office of Management and Budget under Control Number.)


Sec.  __.118  Applications and proposals lacking definite plans for 
involvement of human subjects.

    Certain types of applications for grants, cooperative agreements, 
or contracts are submitted to Federal departments or agencies with the 
knowledge that subjects may be involved within the period of support, 
but definite plans would not normally be set forth in the application 
or proposal. These include activities such as institutional type grants 
when selection of specific projects is the institution's 
responsibility; research training grants in which the activities 
involving subjects remain to be selected; and projects in which human 
subjects' involvement will depend upon completion of instruments, prior 
animal studies, or purification of compounds. Except for research 
excluded under Sec.  __.101(b), waived under Sec.  __.101(i), or 
exempted under Sec.  __.104(d), (e), or (f)(2), no human subjects may 
be involved in any project supported by these awards until the project 
has been reviewed and approved by the IRB, as provided in this policy, 
and certification submitted, by the institution, to the Federal 
department or agency component supporting the research.


Sec.  __.119  Research undertaken without the intention of involving 
human subjects.

    Except for research excluded under Sec.  __.101(b), waived under 
Sec.  __.101(i), or exempted under Sec.  __.104(d), (e), or (f)(2), in 
the event research is undertaken without the intention of involving 
human subjects, but it is later proposed to involve human subjects in 
the research, the research shall first be reviewed and approved by an 
IRB, as provided in this policy, a certification submitted by the 
institution to the Federal department or agency component supporting 
the research, and final approval given to the proposed change by the 
Federal department or agency component.


Sec.  __.120  Evaluation and disposition of applications and proposals 
for research to be conducted or supported by a Federal department or 
agency.

    (a) The department or agency head will evaluate all applications 
and proposals involving human subjects submitted to the Federal 
department or agency through such officers and employees of the Federal 
department or agency and such experts and consultants as the department 
or agency head determines to be appropriate. This evaluation will take 
into consideration the risks to the subjects, the adequacy of 
protection against these risks, the potential benefits of the research 
to the subjects and others, and the importance of the knowledge gained 
or to be gained.
    (b) On the basis of this evaluation, the department or agency head 
may approve or disapprove the application or proposal, or enter into 
negotiations to develop an approvable one.

[[Page 54056]]

Sec.  __.121  [Reserved]


Sec.  __.122  Use of Federal funds.

    Federal funds administered by a Federal department or agency may 
not be expended for research involving human subjects unless the 
requirements of this policy have been satisfied.


Sec.  __.123  Early termination of research support: Evaluation of 
applications and proposals.

    (a) The department or agency head may require that Federal 
department or agency support for any project be terminated or suspended 
in the manner prescribed in applicable program requirements, when the 
department or agency head finds an institution has materially failed to 
comply with the terms of this policy.
    (b) In making decisions about supporting or approving applications 
or proposals covered by this policy the department or agency head may 
take into account, in addition to all other eligibility requirements 
and program criteria, factors such as whether the applicant has been 
subject to a termination or suspension under paragraph (a) of this 
section and whether the applicant or the person or persons who would 
direct or has/have directed the scientific and technical aspects of an 
activity has/have, in the judgment of the department or agency head, 
materially failed to discharge responsibility for the protection of the 
rights and welfare of human subjects (whether or not the research was 
subject to federal regulation).


Sec.  __.124  Conditions.

    With respect to any research project or any class of research 
projects the department or agency head of either the conducting or the 
supporting Federal department or agency may impose additional 
conditions prior to or at the time of approval when in the judgment of 
the department or agency head additional conditions are necessary for 
the protection of human subjects.

DEPARTMENT OF HOMELAND SECURITY

6 CFR Part 46

List of Subjects in 6 CFR Part 46

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Department of Homeland 
Security proposes to add 6 CFR part 46, as set forth at the end of the 
common preamble of this document.

PART 46--PROTECTION OF HUMAN SUBJECTS

Sec.
46.101 To what does this policy apply?
46.102 Definitions for purposes of this policy.
46.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
46.104 Exempt research.
46.105 Protection of biospecimens and identifiable private 
information.
46.106 [Reserved]
46.107 IRB membership.
46.108 IRB functions and operations.
46.109 IRB review of research.
46.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
46.111 Criteria for IRB approval of research.
46.112 Review by institution.
46.113 Suspension or termination of IRB approval of research.
46.114 Cooperative research.
46.115 IRB records.
46.116 General requirements for informed consent.
46.117 Documentation of informed consent.
46.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
46.119 Research undertaken without the intention of involving human 
subjects.
46.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
46.121 [Reserved]
46.122 Use of Federal funds.
46.123 Early termination of research support: Evaluation of 
applications and proposals.
46.124 Conditions.

    Authority: 5 U.S.C. 301; Pub. L. 107-296, sec. 102, 306(c); Pub. 
L. 108-458, sec. 8306.

Reginald Brothers,
Under Secretary for Science and Technology, DHS.

DEPARTMENT OF AGRICULTURE

7 CFR Part 1c

List of Subjects in 7 CFR Part 1c

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Department of 
Agriculture proposes to revise 7 CFR part 1c, as set forth at the end 
of the common preamble of this document.

PART 1c--PROTECTION OF HUMAN SUBJECTS

Sec.
1c.101 To what does this policy apply?
1c.102 Definitions for purposes of this policy.
1c.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
1c.104 Exempt research.
1c.105 Protection of biospecimens and identifiable private 
information.
1c.106 [Reserved]
1c.107 IRB membership.
1c.108 IRB functions and operations.
1c.109 IRB review of research.
1c.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
1c.111 Criteria for IRB approval of research.
1c.112 Review by institution.
1c.113 Suspension or termination of IRB approval of research.
1c.114 Cooperative research.
1c.115 IRB records.
1c.116 General requirements for informed consent.
1c.117 Documentation of informed consent.
1c.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
1c.119 Research undertaken without the intention of involving human 
subjects.
1c.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
1c.121 [Reserved]
1c.122 Use of Federal funds.
1c.123 Early termination of research support: Evaluation of 
applications and proposals.
1c.124 Conditions.

    Authority:  5 U.S.C. 301.

Catherine Woteki
Under Secretary for Research, Education, and Economics, USDA.

DEPARTMENT OF ENERGY

10 CFR Part 745

List of Subjects in 10 CFR Part 745

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Department of Energy 
proposes to revise 10 CFR part 745, as set forth at the end of the 
common preamble of this document.

PART 745--PROTECTION OF HUMAN SUBJECTS

Sec.
745.101 To what does this policy apply?
745.102 Definitions for purposes of this policy.
745.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
745.104 Exempt research.
745.105 Protection of biospecimens and identifiable private 
information.
745.106 [Reserved]
745.107 IRB membership.
745.108 IRB functions and operations.
745.109 IRB review of research.
745.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.

[[Page 54057]]

745.111 Criteria for IRB approval of research.
745.112 Review by institution.
745.113 Suspension or termination of IRB approval of research.
745114 Cooperative research.
745.115 IRB records.
745.116 General requirements for informed consent.
745.117 Documentation of informed consent.
745.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
745.119 Research undertaken without the intention of involving human 
subjects.
745.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
745.121 [Reserved]
745.122 Use of Federal funds.
745.123 Early termination of research support: Evaluation of 
applications and proposals.
745.124 Conditions.

    Authority:  5 U.S.C. 301; 42 U.S.C. 7254.

Elizabeth Sherwood-Randall,
Deputy Secretary of Energy.

NATIONAL AERONAUTICS AND SPACE ADMINISTRATION

14 CFR Part 1230

List of Subjects in 14 CFR Part 1230

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the National Aeronautics 
and Space Administration proposes to revise 14 CFR part 1230, as set 
forth at the end of the common preamble of this document.

PART 1230--PROTECTION OF HUMAN SUBJECTS

Sec.
1230.101 To what does this policy apply?
1230.102 Definitions for purposes of this policy.
1230.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
1230.104 Exempt research.
1230.105 Protection of biospecimens and identifiable private 
information.
1230.106 [Reserved]
1230.107 IRB membership.
1230.108 IRB functions and operations.
1230.109 IRB review of research.
1230.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
1230.111 Criteria for IRB approval of research.
1230.112 Review by institution.
1230.113 Suspension or termination of IRB approval of research.
1230.114 Cooperative research.
1230.115 IRB records.
1230.116 General requirements for informed consent.
1230.117 Documentation of informed consent.
1230.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
1230.119 Research undertaken without the intention of involving 
human subjects.
1230.120 Evaluation and disposition of applications and proposals 
for research to be conducted or supported by a Federal department or 
agency.
1230.121 [Reserved]
1230.122 Use of Federal funds.
1230.123 Early termination of research support: Evaluation of 
applications and proposals.
1230.124 Conditions.

    Authority:  5 U.S.C. 301.

Richard S. Williams,
Chief Health and Medical Officer.

DEPARTMENT OF COMMERCE

15 CFR Part 27

List of Subjects in 15 CFR Part 27

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Department of Commerce 
proposes to revise 15 CFR part 27, as set forth at the end of the 
common preamble of this document.

PART 27--PROTECTION OF HUMAN SUBJECTS

Sec.
27.101 To what does this policy apply?
27.102 Definitions for purposes of this policy.
27.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
27.104 Exempt research.
27.105 Protection of biospecimens and identifiable private 
information.
27.106 [Reserved]
27.107 IRB membership.
27.108 IRB functions and operations.
27.109 IRB review of research.
27.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
27.111 Criteria for IRB approval of research.
27.112 Review by institution.
27.113 Suspension or termination of IRB approval of research.
27.114 Cooperative research.
27.115 IRB records.
27.116 General requirements for informed consent.
27.117 Documentation of informed consent.
27.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
27.119 Research undertaken without the intention of involving human 
subjects.
27.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
27.121 [Reserved]
27.122 Use of Federal funds.
27.123 Early termination of research support: Evaluation of 
applications and proposals.
27.124 Conditions.

    Authority: 5 U.S.C. 301.

James Hock,
Chief of Staff, Department of Commerce.

SOCIAL SECURITY ADMINISTRATION

20 CFR Part 431

List of Subjects in 20 CFR Part 431

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Social Security 
Administration proposes to add 20 CFR part 431, as set forth at the end 
of the common preamble of this document.

PART 431--PROTECTION OF HUMAN SUBJECTS

Sec.
431.101 To what does this policy apply?
431.102 Definitions for purposes of this policy.
431.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
431.104 Exempt research.
431.105 Protection of biospecimens and identifiable private 
information.
431.106 [Reserved]
431.107 IRB membership.
431.108 IRB functions and operations.
431.109 IRB review of research.
431.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
431.111 Criteria for IRB approval of research.
431.112 Review by institution.
431.113 Suspension or termination of IRB approval of research.
431.114 Cooperative research.
431.115 IRB records.
431.116 General requirements for informed consent.
431.117 Documentation of informed consent.
431.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
431.119 Research undertaken without the intention of involving human 
subjects.
431.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
431.121 [Reserved]
431.122 Use of Federal funds.
431.123 Early termination of research support: Evaluation of 
applications and proposals.
431.124 Conditions.


[[Page 54058]]


    Authority: 5 U.S.C. 301; 42 U.S.C. 289(a).

Carolyn W. Colvin,
Acting Commissioner of Social Security.

AGENCY FOR INTERNATIONAL DEVELOPMENT

22 CFR Part 225

List of Subjects in 22 CFR Part 225

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Agency for 
International Development proposes to revise 22 CFR part 225, as set 
forth at the end of the common preamble of this document.

PART 225--PROTECTION OF HUMAN SUBJECTS

Sec.
225.101 To what does this policy apply?
225.102 Definitions for purposes of this policy.
225.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
225.104 Exempt research.
225.105 Protection of biospecimens and identifiable private 
information.
225.106 [Reserved]
225.107 IRB membership.
225.108 IRB functions and operations.
225.109 IRB review of research.
225.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
225.111 Criteria for IRB approval of research.
225.112 Review by institution.
225.113 Suspension or termination of IRB approval of research.
225.114 Cooperative research.
225.115 IRB records.
225.116 General requirements for informed consent.
225.117 Documentation of informed consent.
225.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
225.119 Research undertaken without the intention of involving human 
subjects.
225.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
225.121 [Reserved]
225.122 Use of Federal funds.
225.123 Early termination of research support: Evaluation of 
applications and proposals.
225.124 Conditions.

    Authority:  5 U.S.C. 301.

Wade Warren,
Senior Deputy Assistant Administrator for Global Health, U.S. Agency 
for International Development.

DEPARTMENT OF JUSTICE

28 CFR Part 46

AG Order No. 3553-2015

List of Subjects in 28 CFR Part 46

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Department of Justice 
proposes to revise 28 CFR part 46, as set forth at the end of the 
common preamble of this document.

PART 46--PROTECTION OF HUMAN SUBJECTS

Sec.
46.101 To what does this policy apply?
46.102 Definitions for purposes of this policy.
46.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
46.104 Exempt research.
46.105 Protection of biospecimens and identifiable private 
information.
46.106 [Reserved]
46.107 IRB membership.
46.108 IRB functions and operations.
46.109 IRB review of research.
46.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
46.111 Criteria for IRB approval of research.
46.112 Review by institution.
46.113 Suspension or termination of IRB approval of research.
46.114 Cooperative research.
46.115 IRB records.
46.116 General requirements for informed consent.
46.117 Documentation of informed consent.
46.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
46.119 Research undertaken without the intention of involving human 
subjects.
46.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
46.121 [Reserved]
46.122 Use of Federal funds.
46.123 Early termination of research support: Evaluation of 
applications and proposals.
46.124 Conditions.

    Authority: 5 U.S.C. 301; 28 U.S.C. 509-510.

Sally Quillian Yates,
Deputy Attorney General.

DEPARTMENT OF LABOR

29 CFR Part 21

List of Subjects in 29 CFR Part 21

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Social Security 
Administration proposes to add 29 CFR part 21, as set forth at the end 
of the common preamble of this document.

PART 21--PROTECTION OF HUMAN SUBJECTS

Sec.
21.101 To what does this policy apply?
21.102 Definitions for purposes of this policy.
21.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
21.104 Exempt research.
21.105 Protection of biospecimens and identifiable private 
information.
21.106 [Reserved]
21.107 IRB membership.
21.108 IRB functions and operations.
21.109 IRB review of research.
21.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
21.111 Criteria for IRB approval of research.
21.112 Review by institution.
21.113 Suspension or termination of IRB approval of research.
21.114 Cooperative research.
21.115 IRB records.
21.116 General requirements for informed consent.
21.117 Documentation of informed consent.
21.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
21.119 Research undertaken without the intention of involving human 
subjects.
21.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
21.121 [Reserved]
21.122 Use of Federal funds.
21.123 Early termination of research support: Evaluation of 
applications and proposals.
21.124 Conditions.


[[Page 54059]]


    Authority: 5 U.S.C. 301; 29 U.S.C. 551.

Christopher P. Lu,
Deputy Secretary of Labor.

DEPARTMENT OF DEFENSE

32 CFR Part 219

List of Subjects in 32 CFR Part 219

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Department of Defense 
proposes to revise 32 CFR part 219, as set forth at the end of the 
common preamble of this document.

PART 219--PROTECTION OF HUMAN SUBJECTS

Sec.
219.101 To what does this policy apply?
219.102 Definitions for purposes of this policy.
219.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
219.104 Exempt research.
219.105 Protection of biospecimens and identifiable private 
information.
219.106 [Reserved]
219.107 IRB membership.
219.108 IRB functions and operations.
219.109 IRB review of research.
219.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
219.111 Criteria for IRB approval of research.
219.112 Review by institution.
219.113 Suspension or termination of IRB approval of research.
219.114 Cooperative research.
219.115 IRB records.
219.116 General requirements for informed consent.
219.117 Documentation of informed consent.
219.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
219.119 Research undertaken without the intention of involving human 
subjects.
219.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
219.121 [Reserved]
219.122 Use of Federal funds.
219.123 Early termination of research support: Evaluation of 
applications and proposals.
219.124 Conditions.

    Authority: 5 U.S.C. 301.

Patricia L. Toppings,
OSD Federal Register Liaison, Officer, Department of Defense.

DEPARTMENT OF EDUCATION

34 CFR Part 97

List of Subjects in 34 CFR Part 97

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Department of Education 
proposes to amend 34 CFR part 97 as follows:

 PART 97--PROTECTION OF HUMAN SUBJECTS

0
1. The authority citation for part 97 continues to read as follows:

    Authority: 5 U.S.C. 301; 20 U.S.C. 1221e-3, 3474.

0
2. Subpart A is revised as set forth at the end of the common preamble 
of this document.

Subpart A--Federal Policy for the Protection of Human Subjects 
(Basic ED Policy for Protection of Human Research Subjects)

Sec.
97.101 To what does this policy apply?
97.102 Definitions for purposes of this policy.
97.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
97.104 Exempt research.
97.105 Protection of biospecimens and identifiable private 
information.
97.106 [Reserved]
97.107 IRB membership.
97.108 IRB functions and operations.
97.109 IRB review of research.
97.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
97.111 Criteria for IRB approval of research.
97.112 Review by institution.
97.113 Suspension or termination of IRB approval of research.
97.114 Cooperative research.
97.115 IRB records.
97.116 General requirements for informed consent.
97.117 Documentation of informed consent.
97.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
97.119 Research undertaken without the intention of involving human 
subjects.
97.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
97.121 [Reserved]
97.122 Use of Federal funds.
97.123 Early termination of research support: Evaluation of 
applications and proposals.
97.124 Conditions.

Arne Duncan,
Secretary of Education.

DEPARTMENT OF VETERANS AFFAIRS

38 CFR Part 16

List of Subjects in 38 CFR Part 16

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Department of Veterans 
Affairs proposes to revise 38 CFR part 16, as set forth at the end of 
the common preamble of this document.

PART 16--PROTECTION OF HUMAN SUBJECTS

Sec.
16.101 To what does this policy apply?
16.102 Definitions for purposes of this policy.
16.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
16.104 Exempt research.
16.105 Protection of biospecimens and identifiable private 
information.
16.106 [Reserved]
16.107 IRB membership.
16.108 IRB functions and operations.
16.109 IRB review of research.
16.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
16.111 Criteria for IRB approval of research.
16.112 Review by institution.
16.113 Suspension or termination of IRB approval of research.
16.114 Cooperative research.
16.115 IRB records.
16.116 General requirements for informed consent.
16.117 Documentation of informed consent.
16.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
16.119 Research undertaken without the intention of involving human 
subjects.
16.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
16.121 [Reserved]
16.122 Use of Federal funds.
16.123 Early termination of research support: Evaluation of 
applications and proposals.
16.124 Conditions.


[[Page 54060]]


    Authority: 5 U.S.C. 301; 38 U.S.C. 501, 7331, 7334.

Robert L. Nabors II,
Chief of Staff, U.S. Department of Veterans Affairs,

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 26

List of Subjects in 40 CFR Part 26

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Environmental 
Protection Agency proposes to amend 40 CFR part 26 as follows:

PART 26--PROTECTION OF HUMAN SUBJECTS

0
1. The authority citation for part 26 continues to read as follows:

    Authority: 5 U.S.C. 301; 7 U.S.C. 136a(a) and 136w(a)(1); 21 
U.S.C. 346a(e)(1)(C); sec. 201, Pub. L. 109-54, 119 Stat. 531.

0
2. Subpart A is revised as set forth at the end of the common preamble 
of this document.

Subpart A--Basic EPA Policy for Protection of Subjects in Human 
Research Conducted or Supported by EPA

Sec.
26.101 To what does this policy apply?
26.102 Definitions for purposes of this policy.
26.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
26.104 Exempt research.
26.105 Protection of biospecimens and identifiable private 
information.
26.106 [Reserved]
26.107 IRB membership.
26.108 IRB functions and operations.
26.109 IRB review of research.
26.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
26.111 Criteria for IRB approval of research.
26.112 Review by institution.
26.113 Suspension or termination of IRB approval of research.
26.114 Cooperative research.
26.115 IRB records.
26.116 General requirements for informed consent.
26.117 Documentation of informed consent.
26.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
26.119 Research undertaken without the intention of involving human 
subjects.
26.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
26.121 [Reserved]
26.122 Use of Federal funds.
26.123 Early termination of research support: Evaluation of 
applications and proposals.
26.124 Conditions.

A. Stanley Meiburg,
Acting Deputy Administrator.

DEPARTMENT OF HEALTH AND HUMAN SERVICES

45 CFR Part 46

List of Subjects in 45 CFR Part 46

    Human research subjects, Reporting and record-keeping requirements, 
Research.

    For the reasons stated in the preamble, the Department of Health 
and Human Services proposes to amend 45 CFR part 46 as follows:

PART 46--PROTECTION OF HUMAN SUBJECTS

0
1. The authority citation for part 46 is revised to read as follows:

    Authority: 5 U.S.C. 301; 42 U.S.C. 289.

0
2. Subpart A is revised as set forth at the end of the common preamble 
of this document.

Subpart A--Basic HHS Policy for Protection of Human Research 
Subjects

Sec.
46.101 To what does this policy apply?
46.102 Definitions for purposes of this policy.
46.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
46.104 Exempt research.
46.105 Protection of biospecimens and identifiable private 
information.
46.106 [Reserved]
46.107 IRB membership.
46.108 IRB functions and operations.
46.109 IRB review of research.
46.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
46.111 Criteria for IRB approval of research.
46.112 Review by institution.
46.113 Suspension or termination of IRB approval of research.
46.114 Cooperative research.
46.115 IRB records.
46.116 General requirements for informed consent.
46.117 Documentation of informed consent.
46.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
46.119 Research undertaken without the intention of involving human 
subjects.
46.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
46.121 [Reserved]
46.122 Use of Federal funds.
46.123 Early termination of research support: Evaluation of 
applications and proposals.
46.124 Conditions.

Sylvia M. Burwell,
Secretary, HHS.

NATIONAL SCIENCE FOUNDATION

45 CFR Part 690

List of Subjects in 45 CFR Part 690

    Human research subjects, Reporting and record-keeping requirements, 
Research.
    For the reasons stated in the preamble, the National Science 
Foundation proposes to revise 45 CFR part 690, as set forth at the end 
of the common preamble of this document.

PART 690--PROTECTION OF HUMAN SUBJECTS

Sec.
690.101 To what does this policy apply?
690.102 Definitions for purposes of this policy.
690.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
690.104 Exempt research.
690.105 Protection of biospecimens and identifiable private 
information.
690.106 [Reserved]
690.107 IRB membership.
690.108 IRB functions and operations.
690.109 IRB review of research.
690.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
690.111 Criteria for IRB approval of research.
690.112 Review by institution.
690.113 Suspension or termination of IRB approval of research.
690.114 Cooperative research.
690.115 IRB records.
690.116 General requirements for informed consent.
690.117 Documentation of informed consent.
690.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
690.119 Research undertaken without the intention of involving human 
subjects.
690.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
690.121 [Reserved]
690.122 Use of Federal funds.
690.123 Early termination of research support: Evaluation of 
applications and proposals.
690.124 Conditions.


[[Page 54061]]


    Authority: 5 U.S.C. 301.

Lawrence Rudolph,
General Counsel.

DEPARTMENT OF TRANSPORTATION

49 CFR Part 11

List of Subjects in 49 CFR Part 11

    Human research subjects, Reporting and record-keeping requirements, 
Research.
    For the reasons stated in the preamble, the Department of 
Transportation proposes to revise 49 CFR part 11, as set forth at the 
end of the common preamble of this document.

PART 11--PROTECTION OF HUMAN SUBJECTS

Sec.
11.101 To what does this policy apply?
11.102 Definitions for purposes of this policy.
11.103 Assuring compliance with this policy--research conducted or 
supported by any Federal department or agency.
11.104 Exempt research.
11.105 Protection of biospecimens and identifiable private 
information.
11.106 [Reserved]
11.107 IRB membership.
11.108 IRB functions and operations.
11.109 IRB review of research.
11.110 Expedited review procedures for certain kinds of research 
involving no more than minimal risk, and for minor changes in 
approved research.
11.111 Criteria for IRB approval of research.
11.112 Review by institution.
11.113 Suspension or termination of IRB approval of research.
11.114 Cooperative research.
11.115 IRB records.
11.116 General requirements for informed consent.
11.117 Documentation of informed consent.
11.118 Applications and proposals lacking definite plans for 
involvement of human subjects.
11.119 Research undertaken without the intention of involving human 
subjects.
11.120 Evaluation and disposition of applications and proposals for 
research to be conducted or supported by a Federal department or 
agency.
11.121 [Reserved]
11.122 Use of Federal funds.
11.123 Early termination of research support: Evaluation of 
applications and proposals.
11.124 Conditions.

    Authority: 5 U.S.C. 301.

Anthony R. Foxx,
Secretary of Transportation.
[FR Doc. 2015-21756 Filed 9-2-15; 11:15 am]
BILLING CODE 4150-36-P