[Federal Register Volume 74, Number 88 (Friday, May 8, 2009)]
[Proposed Rules]
[Pages 21610-21613]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-10666]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Part 50

45 CFR Part 94

[Docket No. NIH-2008-0002]
RIN 0925-AA53


Responsibility of Applicants for Promoting Objectivity in 
Research for Which Public Health Service Funding Is Sought and 
Responsible Prospective Contractors; Request for Comments

AGENCY: Department of Health and Human Services.

ACTION: Advance notice of proposed rulemaking.

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

SUMMARY: On behalf of the Department of Health and Human Services (HHS) 
and the Public Health Service (PHS), a component of the HHS, the 
National Institutes of Health (NIH) seeks comments from the public on 
whether the HHS should amend its regulations on the responsibility of 
applicants for promoting objectivity in research for which phs funding 
is sought and on responsible prospective. We are interested 
particularly in receiving comments on the issues presented below from 
the general public, individual Investigators, scientific societies and 
associations, Members of Congress, other Federal agencies that support 
or conduct research, and institutions that receive PHS funds to conduct 
or support biomedical or behavioral research.

DATES: To assure consideration, comments must be received by July 7, 
2009.

ADDRESSES: Individuals and organizations interested in submitting 
comments, identified by RIN 0925-AA53 and Docket Number NIH-2008-0002, 
may do so by any of the following methods:

Electronic Submissions

    You may submit electronic comments in the following way:
     The Regulations.gov portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
    To ensure timelier processing of comments, NIH is no longer 
accepting comments submitted to the agency by e-mail. The NIH 
encourages you to continue to submit electronic comments by using the 
Regulations.gov portal: http://www.regulations.gov.

Written Submissions

    You may send written submissions in the following ways:
     Fax: 301-402-0169.
     Mail: Attention: Jerry Moore, NIH Regulations Officer, 
NIH, Office of Management Assessment, 6011 Executive Boulevard, Suite 
601, MSC 7669, Rockville, MD 20852-7669.
     Hand Delivery/Courier (for paper, disk, or CD-ROM 
submissions): Attention: Jerry Moore, 6011 Executive Boulevard, Suite 
601, Rockville, MD 20852-7669.

Docket

    For access to the docket to read background documents or comments 
received, go to the Regulations.gov portal and insert the docket number 
provided in brackets in the heading on page one of this document into 
the ``Search'' box and follow the prompts.

FOR FURTHER INFORMATION CONTACT: Jerry Moore at the address above, or 
telephone 301-496-4607 (not a toll-free number) concerning questions 
about the rulemaking process; and Sally J. Rockey, PhD, Deputy 
Director, Office of Extramural Research, One Center Drive, Building 1, 
Room 142, Bethesda, MD 20892, e-mail FCOI-ANPRM@NIH.GOV concerning 
programmatic questions.

SUPPLEMENTARY INFORMATION: Proper stewardship of Federal funds includes 
ensuring objectivity of results by protecting federally funded research 
from compromise by financial conflicts of interest (FCOI).
    In 1995, the PHS and the Office of the Secretary of Health and 
Human Services published the regulations at 42 CFR Part 50 Subpart F 
and 45 CFR Part 94, designed to promote objectivity in PHS-funded 
research.\1\ The regulations are applicable to Institutions \2\ that 
apply for PHS funding for research (except for Small Business 
Innovation Research (SBIR)/Small Business Technology Transfer Research 
(STTR) Phase I applications/proposals) and, through implementation of 
the regulations by these Institutions, to each Investigator \3\ 
participating in the research. Generally, under the regulations:
---------------------------------------------------------------------------

    \1\ 48 CFR Subpart 9.1, ``Responsible Prospective Contractors,'' 
and 48 CFR Subpart 9.5, ``Organizational and Consultant Conflicts of 
Interest,'' also address conflicts of interest in Federally-funded 
projects. These provisions apply only to acquisitions, not to grants 
or cooperative agreements.
    \2\ An ``Institution'' is defined under 42 CFR Part 50, Subpart 
F, as any domestic or foreign, public or private, entity or 
organization (excluding a Federal agency), and under 45 CFR Part 94 
as any public or private entity or organization (excluding a Federal 
agency) that (1) submits a proposal for a research contract whether 
in response to a solicitation from the PHS or otherwise, or (2) that 
assumes the legal obligation to carry out the research required 
under the contract. See 42 CFR 50.603; 45 CFR 94.3.
    \3\ An ``Investigator'' is defined under the regulations as the 
principal investigator and any other person who is responsible for 
the design, conduct, or reporting of research funded by PHS, or 
proposed for such funding. For purposes of the regulatory 
requirements relating to financial interests, the term 
``Investigator'' includes the Investigator's spouse and dependent 
children. See 42 CFR 50.603; 45 CFR 94.3.
---------------------------------------------------------------------------

     The Institution is responsible for complying with the 
regulations, including developing and maintaining a written and 
enforced policy; managing, reducing, or eliminating identified 
conflicts; and reporting identified conflicts to the PHS funding 
component. The reports denote the existence of a conflict and assure 
that it has been managed, reduced, or eliminated.
     The participating Investigators are responsible for 
complying with their Institution's written Financial Conflict of 
Interest (FCOI) policy and for disclosing their Significant Financial 
Interests \4\ (SFI) to their Institution.
---------------------------------------------------------------------------

    \4\ A ``Significant Financial Interest'' is defined under the 
regulation as anything of monetary value, including but not limited 
to (1) Salary or other payments for services (e.g., consulting fees 
or honoraria); (2) equity interests (e.g., stocks, stock options or 
other ownership interests); and (3) intellectual property rights 
(e.g., patents, copyrights and royalties from such rights). The term 
does not include (1) Salary, royalties, or other remuneration from 
the institution; (2) any ownership interests in the institution, if 
the institution is an applicant under the SBIR program; (3) income 
from seminars, lectures, or teaching engagements sponsored by public 
or nonprofit entities; (4) income from service on advisory 
committees or review panels for public or nonprofit entities; (5) an 
equity interest that, when aggregated for the investigator and the 
investigator's spouse and dependent children, does not exceed 
$10,000 in value as determined through reference to public prices or 
other reasonable measures of fair market value, and does not 
represent more than a five percent ownership interest in any single 
entity; and (6) salary, royalties, or other payments that when 
aggregated for the investigator and the investigator's spouse and 
dependent children over the next twelve months are not expected to 
exceed $10,000. 42 CFR 50.603; 45 CFR 94.3.

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

[[Page 21611]]

     The PHS funding components are responsible for overseeing 
Institutional compliance with the regulations.
    Ensuring objectivity in research requires a commitment from 
Institutions and their Investigators to complete disclosure, 
appropriate review, and robust management of identified conflicts 
consistent with the level of risk presented. The existing regulations 
were designed to provide standards to ensure that the design, conduct, 
or and reporting of PHS-funded research is not biased by any FCOI.
    In the intervening years since the publication of these 
regulations, the pace of translation of new discoveries from the 
research bench into effective treatment of patients has significantly 
accelerated. As a result, the biomedical research enterprise in the 
United States is extensive and growing in size and complexity. 
Researchers frequently work in multidisciplinary teams to develop new 
strategies and approaches for translating basic research into clinical 
application. In addition, these newer translational strategies often 
involve complex collaborations between investigators and the private 
sector. Together, these factors may generate an increased potential of 
investigators to hold financial interests in multiple sources which, if 
not reported and appropriately managed, reduced, or eliminated, could 
introduce bias into the conduct of their research. Recognition of the 
growing complexity of biomedical research, the increased interaction 
between Government and the private sector in meeting common public 
health goals, and recent public scrutiny have raised the question of 
whether a more rigorous approach to Investigator disclosure, management 
of conflicts, and Federal oversight is required.
    Ensuring the objectivity of research results requires a commitment 
to uphold the following principles:
    1. Research must be conducted with transparency and the highest 
scientific and ethical standards in a manner that promotes and respects 
the rights, safety, and welfare of all human research participants.
    2. Appropriate interactions and relationships between government, 
academia, and industry, which do not compromise objectivity in 
research, frequently have beneficial outcomes and should be encouraged.
    3. The integrity of the scientific record is critical to the 
conduct of science.
    4. Risk management is essential in evaluating and managing conflict 
of interest; risk management should be commensurate with the level of 
risk of the research.
    5. Complete and timely disclosure of financial interests and 
effective management of conflicts of interest are essential to ensuring 
objectivity in research.
    For the reasons cited above, we are considering whether to revise 
the current regulations to provide Institutions with a more 
comprehensive set of guidelines based on these five principles. The 
complex and controversial issues surrounding FCOI warrant a carefully 
considered, open dialogue with all affected parties. Consequently, we 
invite public comments on all aspects of potential regulation in this 
area, and particularly on the following issues:

I. Expanding the Scope of the Regulation & Disclosure of Interests

    The regulations are applicable to Institutions that apply for PHS 
funding for research and, through implementation of the regulations by 
each Institution, to each Investigator participating in such research. 
However, the regulations do not apply to Phase I SBIR/STTR applications 
(42 CFR 50.602, 45 CFR 94.2).
    The regulations require that Investigators disclose to the 
Institution only those Significant Financial Interests (SFI) (1) that 
would reasonably appear to be affected by the research for which 
funding is sought from the PHS; and (2) in entities whose financial 
interests would reasonably appear to be affected by the research (42CFR 
50.604(c)(1); 45 CFR 94.4(c)(1)).
    a. Should the regulations be expanded so that they also apply to 
Phase I SBIR/STTR research applications/proposals for PHS funding?
    b. In May 2004, HHS issued a guidance document entitled, 
``Financial Relationships and Interests in Research Involving Human 
Subjects: Guidance for Human Subject Protection'' that raises points to 
consider in determining whether specific financial interests, including 
Institutional financial interests, in research affect the rights and 
welfare of human subjects and if so, what actions could be considered 
to protect those subjects. In February 2008, the Association of 
American Medical Colleges (AAMC) and the Association of American 
Universities (AAU) Advisory Committee on Financial Conflicts of 
Interest in Human Subjects Research issued a report, ``Protecting 
Patients, Preserving Integrity, Advancing Health: Accelerating the 
Implementation of COI Policies in Human Subjects Research,'' which 
offered a number of recommendations designed to enhance Institutional 
conflict of interest policies. One recommendation was that 
investigators conducting human subjects research should be required to 
report all of their outside financial interests directly or indirectly 
related to their professional responsibilities to their Institution, 
regardless of dollar amount and regardless of whether or not the 
investigator believes that the reported financial interests might 
reasonably appear to be affected by his or her current or anticipated 
research. In light of the above, should Investigators be required to 
disclose to their Institutions all Significant Financial Interests that 
are related to their Institutional responsibilities? Would this 
expanded disclosure allow the Institution to better determine which of 
these Significant Financial Interests constitute a FCOI?

II. Definition of ``Significant Financial Interest''

    A ``Significant Financial Interest'' is defined by the current 
regulations as anything of monetary value, including but not limited 
to:
     Salary or other payments for services (e.g., consulting 
fees or honoraria);
     Equity interests (e.g., stocks, stock options or other 
ownership interests);
     Intellectual property rights (e.g., patents, copyrights 
and royalties from such rights).
    The term does not include the following types of financial 
interests:
     Salary, royalties, or other remuneration from the 
Institution;
     Any ownership interests in the Institution, if the 
Institution is an applicant under the SBIR/STTR program;
     Income from seminars, lectures, or teaching engagements 
sponsored by public or nonprofit entities;
     Income from service on advisory committees or review 
panels for public or nonprofit entities;
     An equity interest that, when aggregated for the 
Investigator and the Investigator's spouse and dependent children, does 
not exceed $10,000 in value as determined through reference to public 
prices or other reasonable measures of fair market value, and does not 
represent more than a five percent ownership interest in any single 
entity;
     Salary, royalties or other payments that when aggregated 
for the Investigator and the Investigator's spouse and dependent 
children over the next twelve

[[Page 21612]]

months, are not expected to exceed $10,000. (42 CFR 50.603; 45 CFR 
94.3).
    a. Should the current exemptions be maintained?
     If so, are the current de minimis thresholds ($10,000 and 
5 percent ownership interest in any single entity) reasonable? If not, 
how should the de minimis thresholds be changed? Should these 
thresholds be the same for all types of research?
     If not, which exemptions should be reconsidered, and why?
    b. Should certain Significant Financial Interests (i.e., 
Significant Financial Interests received from specific sources or 
related to certain types of research) automatically be considered a 
FCOI under the regulations? If so, what types of Significant Financial 
Interests?

III. Identification and Management of Conflicts by Institutions

    The regulations require that an official(s) designated by the 
Institution review all financial disclosures; determine whether a 
financial conflict of interest exists; and, if so, determine what 
actions the Institution should take to manage, reduce, or eliminate the 
conflict of interest (42 CFR. 50.605; 45 CFR 94.5). The regulations 
provide that a conflict of interest exists when the designated 
official(s) reasonably determines that a Significant Financial Interest 
could directly and significantly affect the design, conduct, or 
reporting of the research funded by the PHS (42 CFR 50.605; 45 CFR 
94.5). The regulations currently do not define the term ``designated 
Institutional official(s)'', or mandate specific actions that 
Institutions must take to manage, reduce or eliminate particular types 
of FCOIs.
    a. Should large Institutions (defined as greater than 50 employees) 
be required to establish an independent committee to review financial 
disclosures, and require that committee to report to an organizational 
level within the Institution that is not conflicted by the short-term 
financial interests of the Investigator or Institution? Would a 50 
employee threshold reasonably balance the risk of a more relaxed 
requirement for smaller Institutions against the burden imposed by 
requiring an independent panel for these evaluations?
    b. For certain types of research, should the Institution be 
required to develop a conflict management plan when the Institution 
decides to manage or reduce, rather than eliminate, the conflict? If 
so, for which types of research? Should there be prescribed standards 
for the conflict management plans? Should the Institution be required 
to submit this plan to the PHS funding component when it reports the 
existence of a conflict to the component?
    c. Should Investigators who are involved in participant selection, 
the informed consent process, and clinical management of a trial, be 
prohibited from having a Significant Financial Interest in any company 
whose interests could be affected by their research or clinical trial? 
If so, what special circumstances would justify waiving this condition, 
if any?
    d. Should the regulations prescribe specific approaches for the 
management, reduction, or elimination of particular types of FCOI? If 
so, for which types of FCOI? Which approaches?
    e. Should specific requirements related to the identification, 
management, and reporting of FCOI be established for subrecipients 
(i.e., subgrantees, contractors, subcontractors, collaborators)?
    f. Should amounts received by Investigators from certain kinds of 
organizations be limited to certain maximum thresholds if an 
Investigator is supported with PHS research funds? If so, which kinds 
of organizations? At what thresholds?

IV. Assuring Institutional Compliance

    Under the current regulations, the PHS funding component may at any 
time inquire into the Institutional procedures and actions regarding 
conflicting financial interests in PHS-funded research, including a 
requirement for submission, or review on site, of all records pertinent 
to compliance with the regulation (42 CFR 50.606; 45 CFR 94.6). On the 
basis of its review of records and/or other information that may be 
available, the PHS funding component may decide that a particular 
conflict of interest will bias the objectivity of the research it funds 
to such an extent that further corrective action is needed or that the 
Institution has not managed, reduced, or eliminated the conflict of 
interest in accordance with the regulation(s) (42 CFR 50.606; 45 CFR 
94.6). The PHS funding component may determine that suspension of 
funding/the issuance of a Stop Work order is necessary until the matter 
is resolved(42 CFR 50.606; 45 CFR 94.6).
    a. Should the regulations enhance existing enforcement options in 
the event of noncompliance?
    b. Should Investigators be required under the regulations to 
complete routine FCOI training?
    c. Should independent confirmation of an Institution's compliance 
with the regulation be required? If so, what should this confirmation 
look like (e.g., accreditation by an outside body, an independent 
audit)?

V. Requiring Institutions to Provide Additional Information to the PHS

    Under the current regulations, prior to spending any funds under an 
award, the Institution must report to the PHS funding component the 
existence of any conflicting financial interest found by the 
Institution and assure that the interest has been managed, reduced, or 
eliminated in accordance with the regulation(s) (42 CFR 50.604(g)(2), 
45 CFR 94.4(g)(2)). The regulations do not require the Institution to 
report to PHS officials the nature of the interest or other details (42 
CFR 50.604(g)(2), 45 CFR 94.4(g)(2)).
    a. Should Institutions be required to submit to the PHS funding 
component additional information on any identified conflict? If they 
should not be required to submit additional information for all 
identified conflicts, should they be required to submit additional 
information for identified conflicts involving certain types of 
research? If so, for which types of research? What kind of information 
would provide valuable data to the PHS funding component in evaluating 
these reports and the potential risk of bias in conduct of research?

VI. Institutional Conflict of Interest

    Institutional conflict of interest is currently not addressed by 
the regulations, although there has been movement in the research 
community toward incorporating Institutional standards in conflict of 
interest policies (see, for example, the February 2008 AAMC/AAU report, 
``Protecting Patients, Preserving Integrity, Advancing Health: 
Accelerating the Implementation of COI Policies in Human Subjects 
Research''), and some Institutions have adopted such standards. This is 
an area of increasing concern. If the regulation were to be amended to 
address Institutional conflict of interest, how should it address the 
following issues?
    a. How would Institutional conflict of interest be defined?
    b. What would an Institutional conflict of Interest policy address 
in order to assure the PHS of objectivity in research?


[[Page 21613]]


    Dated: February 2, 2009.
Raynard S. Kington,
Acting Director, National Institutes of Health.
    Approved: April 9, 2009.
Charles E. Johnson,
Acting Secretary.
[FR Doc. E9-10666 Filed 5-7-09; 8:45 am]
BILLING CODE 4140-01-P