[Federal Register Volume 80, Number 3 (Tuesday, January 6, 2015)]
[Notices]
[Pages 511-512]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-30964]
[[Page 511]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Announcement of a Draft NIH Policy on the Use of a Single
Institutional Review Board for Multi-Site Research
SUMMARY: On December 3, 2014, the National Institutes of Health (NIH)
published a request for public comments in the NIH Guide for Grants and
Contracts on a draft policy to promote the use of a single
Institutional Review Board of record for domestic sites of multi-site
studies funded by the NIH. See Guide notice NOT-OD-15-026 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-026.html. NIH is
publishing this notice in order to inform readers of the Federal
Register about the draft policy and the opportunity to comment.
DATES: The deadline for receiving comments on the draft policy is no
later than 5:00 p.m. on January 29, 2015.
ADDRESSES: Comments may be submitted by any of the following methods:
Email: [email protected]
Fax: 301-496-9839
Mail/Hand delivery/Courier: Office of Clinical Research
and Bioethics Policy, Office of Science Policy, National Institutes of
Health, 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892.
FOR FURTHER INFORMATION CONTACT: Office of Clinical Research and
Bioethics Policy, Office of Science Policy, National Institutes of
Health, 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892, 301-496-
9838, [email protected].
SUPPLEMENTARY INFORMATION:
Background
The National Institutes of Health (NIH) is dedicated to improving
the health of Americans by conducting and funding biomedical research
through an extensive portfolio of human subjects research. While NIH-
funded investigators must adhere to regulations for the protection of
human subjects, the agency also looks for ways to reduce procedural
inefficiencies so that human subjects research can proceed efficiently
without compromising ethical principles and protections.
The Department of Health and Human Services (HHS) regulations for
the Protection of Human Subjects at 45 CFR part 46 requires
Institutional Review Board (IRB) review of non-exempt HHS conducted or
supported human subjects research. IRBs are responsible for performing
an ethical review of studies involving human subjects. Research
protocols and informed consent documents must be approved by an IRB
prior to the commencement of human subjects research. In 1975, when the
HHS regulations for protection of human subjects were first
published,\1\ most clinical research was conducted primarily at a
single institution. Since then, the research landscape has evolved, and
many studies are carried out at multiple sites.
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\1\ 40 FR 11854 (March 13, 1975)
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In order to avoid duplication of the effort, both the HHS
regulations at 45 CFR part 46 and the IRB regulations of the Food and
Drug Administration (FDA) at 21 CFR part 56 allow institutions that
participate in multi-site studies to use joint review, rely on the
review of another qualified IRB, or establish other arrangements.\2\
FDA and the Office for Human Research Protections (OHRP) have also
issued guidance on this topic.3 4 However, too few
institutions involved in multi-site studies are taking advantage of the
option.\5\
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\2\ 45 CFR part 46.114 and 21 CFR part 56.114
\3\ See http://www.fda.gov/RegulatoryInformation/Guidances/ucm127004.htm
\4\ See http://www.hhs.gov/ohrp/policy/protocol/cirb20100430.html
\5\ Flynn KE, et al. Using central IRBs for multicenter clinical
trials in the United States. PLoS ONE. 2013; 8(1):e54999.
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Proponents of the single IRB model maintain that review of a multi-
site study by the IRB of each participating site involves significant
administrative burden in terms of IRB staff and members' time to
perform duplicative reviews. When each participating institution's IRB
conducts a review, the process can take many months and significantly
delay the initiation of research projects and recruitment of human
subjects into research studies. Use of single IRBs in multi-site
studies, on the other hand, has been shown to decrease approval times
for clinical protocols and may be more cost effective than local IRB
review.\6\
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\6\ Wagner TH, et al. Costs and benefits of the National Cancer
Institute Central Institutional Review Board. J Clin Oncol. 2010;
28:662-666.
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Importantly, there is no evidence that multiple IRB reviews enhance
protections for human subjects. In fact, the use of single IRBs may
lead to enhanced protections for research participants by eliminating
the problem of distributed accountability, minimizing institutional
conflicts of interest, and refocusing IRB time and resources toward
review of other studies.7 8 With regard to assuring that
local perspectives are addressed, the assessment of a study's risks and
benefits and the adequacy of the informed consent should not generally
require the perspective of a local IRB. Local contextual issues
relevant to most studies (e.g., investigator competence and site
suitability) can be addressed through mechanisms other than local IRB
review, such as the involvement of ad hoc members or consultants with
the necessary specialized knowledge or expertise or by submission of
information by the individual site(s). Even when certain vulnerable
populations are targeted for recruitment, such alternative approaches
may be appropriate.
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\7\ Emanuel EJ et al. Oversight of human participants research:
identifying problems to evaluate reform proposals. Ann Intern Med.
2004; 141(4): 282-291.
\8\ Menikoff J. The paradoxical problem with multiple-IRB
review. N Engl J Med. 2010; 367:1591-1593.
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Several extramural NIH programs already support the use of a single
IRB for multi-sites studies. For example, the National Cancer Institute
has had a Central Institutional Review Board (CIRB) in place for the
review of NCI-sponsored clinical trials since 1999. The National
Institute of Neurological Disorders and Stroke has incorporated the use
of a single IRB for its Network for Excellence in Neuroscience Clinical
Trials (NeuroNEXT) and Network for Stroke Research
(NIHStrokeNet).9 10
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\9\ See http://www.neuronext.org/researchers and http://
www.nihstrokenet.org/research
\10\ Kaufmann P et al. Central institutional review board review
for an academic trial network. Acad Med. 2014; doi: 10.1097/
ACM.0000000000000562.
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The draft Policy proposes that NIH funded institutions will be
expected to use a single IRB of record for domestic sites of multi-site
studies unless there is justification for an exception (see exceptions
below). The draft Policy applies to all domestic sites participating in
NIH conducted or supported multi-site studies, whether supported
through grants, contracts, or the NIH intramural program. By expecting
all domestic multi-site studies to use a single IRB, this Policy should
help achieve greater efficiencies and speed the initiation of studies
across NIH's entire clinical research portfolio. This Policy is also in
keeping with one of the proposed changes being considered to the Common
Rule.\11\
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\11\ An Advance Notice of Proposed Rulemaking issued in 2011
sought public comment on proposed changes to seven regulatory areas,
including requiring the use of a single IRB for domestic sites in
multi-site studies. Most commenters supported the idea of requiring
the use of a single IRB for review of multi-site studies, especially
for cooperative clinical trials, and agree that such a mandate would
help speed the initiation of multi-site studies. Some commenters
were concerned that the use of a single IRB could lead to increased
liability and diminished accountability for participating sites, and
decreased consideration of local context. See http://www.gpo.gov/fdsys/pkg/FR-2011-07-26/html/2011-18792.htm
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[[Page 512]]
Request for Comments
NIH encourages the public to provide comments on any aspect of the
draft policy outlined below. Comments should be submitted
electronically by January 29, 2015, to the Office of Clinical Research
and Bioethics Policy, Office of Science Policy, NIH, via email at
[email protected]; mail to 6705 Rockledge Drive, Suite 750,
Bethesda, MD 20892; or fax at 301-496-9839. Submitted comments are
considered public information; private or confidential information
should not be submitted. Comments may be posted along with the
submitter's name and affiliation on the OCRBP Web site after the public
comment period closes.
Draft NIH Policy on the Use of a Single Institutional Review Board for
Multi-Site Research
Purpose. The purpose of this Policy is to increase the use of
single Institutional Review Boards (IRB) for multi-site studies funded
by the National Institutes of Health (NIH). Its goal is to enhance and
streamline the process of IRB review and reduce inefficiencies so that
research can proceed efficiently without compromising ethical
principles and protections.
Scope. NIH generally expects all domestic sites of multi-site NIH-
funded studies to use a single IRB of record. The Policy applies to all
domestic sites participating in NIH conducted or supported multi-site
studies, whether supported through grants, contracts, or the NIH
intramural program. While foreign sites in multi-site studies will not
be expected to follow this Policy, they may elect to do so.
Responsibilities. All sites participating in a multi-site study
will be expected to rely on a single IRB to carry out the functions
that are required for institutional compliance with IRB review set
forth in the HHS regulations for the Protection of Human Subjects. The
single IRB will be the IRB of record for the other participating sites.
The single IRB will be accountable for compliance with regulatory
requirements for IRBs specified under the HHS regulations at 45 CFR
part 46, such as providing initial and continuing review of the
research.\12\ All participating sites will be responsible for meeting
other regulatory obligations, such as obtaining informed consent,
overseeing the implementation of approved protocols, and, reporting
unanticipated problems and adverse events to the single IRB of record.
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\12\ On March 5, 2009, OHRP published an ANPRM requesting public
comments on whether OHRP should pursue rulemaking to hold
institutional review boards and institutions or organizations
operating them directly accountable for compliance with the
provisions of 45 CFR part 46 that relate to IRB responsibilities. In
the ANPRM, OHRP identified: Responsibilities that may be unique to
IRBs and the institutions operating them; responsibilities that may
be unique to institutions engaged in human subjects research; and,
responsibilities that may be fulfilled by either IRBs/IORGs or
institutions engaged in human subjects research. See http://www.gpo.gov/fdsys/pkg/FR-2009-03-05/pdf/E9-4628.pdf.
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Agreements between the single IRB of record and other participating
sites will be needed in accordance with 45 CFR part 46. IRB
Authorization Agreements will document the delegation of
responsibilities of IRB review to the designated IRB of record and that
IRB site's acceptance of the responsibilities. The agreement will set
forth the specific responsibilities of each participating site.
Participating sites will then rely on the IRB of record to satisfy the
regulatory requirements relevant to the IRB review. The awardee or lead
site for an NIH-funded, multi-site study will be responsible for
maintaining authorization agreements and should be prepared to provide
copies of the authorization agreements and other necessary
documentation to the NIH funding Institute or Center upon request. As
necessary, mechanisms should be established to enable the single IRB of
record to consider local context issues during its deliberations. A
duplicate IRB review at a participating site would be counter to the
intent and goal of the Policy, but the Policy does not prohibit any
participating site from carrying out its own IRB review. If this
approach is taken, the participating site should expect to bear the
cost of the additional review.
Identification of the IRB that will serve as the single IRB of
record will be the responsibility of the extramural applicant or
offerer, or the intramural principal investigator. The funding NIH
Institute or Center has final decisional authority for approving the
selected single IRB. Use of the designated single IRB will be a term
and condition of award. If the agreed-upon single IRB is a fee-based
IRB, these costs will be included in the Notice of Award as a direct
cost.
Compliance with this Policy will be a term and condition in the
Notice of Award and a contract requirement in the Contract Award.
Exceptions. Exceptions to the expectation to use a single IRB may
be made with appropriate justification. Exceptions will be allowed only
if the designated single IRB is unable to meet the needs of specific
populations or where local IRB review is required by federal, tribal,
or state laws or regulations.\13\
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\13\ For example, FDA-regulated research involving a device is
required to have local IRB review under 21 U.S.C. 360j(g)(3)(A)).
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Effective Date. The Policy applies to all new grant applications
(Type 1 and 2) and contract proposals with receipt dates after [date to
be determined]. It will also apply to intramural multi-site studies
submitted for initial review after that date.\14\
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\14\ When a final policy is issued, NIH will also provide more
specific procedural guidance to facilitate implementation.
Dated: December 24, 2014.
Lawrence Tabak,
Principal Deputy Director,
[FR Doc. 2014-30964 Filed 1-5-15; 8:45 am]
BILLING CODE 4140-01-P