[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