[Federal Register Volume 74, Number 42 (Thursday, March 5, 2009)]
[Proposed Rules]
[Pages 9578-9583]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-4628]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
45 CFR Part 46
Office for Human Research Protections; Institutional Review
Boards
AGENCY: Department of Health and Human Services, Office of the
Secretary, Office of Public Health and Science, Office for Human
Research Protections.
ACTION: Advanced notice of proposed rulemaking; request for comments.
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SUMMARY: The Office for Human Research Protections (OHRP), Office of
Public Health and Science is seeking information and comments on
whether OHRP should pursue a notice of proposed rulemaking (NPRM) to
enable OHRP to hold institutional review boards (IRB) and the
institutions or organizations operating the IRBs, hereafter referred to
as the IRB organizations (IORG), directly accountable for meeting
certain regulatory requirements of the Department of Health and Human
Services (HHS) regulations for the protection of human subjects. OHRP
is contemplating this regulatory change to encourage institutions to
rely on IRBs that are operated by another institution or organization,
when appropriate. Historically, OHRP has only enforced compliance with
45 CFR part 46 through the institutions that were engaged in human
subjects research. This has been the case even in circumstances when a
regulatory violation was directly related to the responsibilities of an
external IRB that was designated on the engaged institution's assurance
of compliance with OHRP. OHRP is considering whether to pursue a
regulatory change that would enable the Department to hold IRBs and
IORGs directly accountable for compliance with the provisions of 45 CFR
part 46 that relate to an IRB's or IORG's responsibilities. OHRP
believes that such a regulatory change in its enforcement authority may
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, OHRP believes
that this will reduce administrative burdens such as the time
associated with IRB review for multi-site studies, the time devoted by
IRB staff and investigators to duplicative IRB review, and the time and
personnel costs associated with operating an IRB for those institutions
that choose not to establish an internal IRB--without diminishing human
subject protections. This request for information and comments stems
from interest in this issue from the Secretary's Advisory Committee on
Human Research Protections (SACHRP) and others, as well as two meetings
on alternative IRB models that OHRP co-sponsored in November 2005 and
November 2006 along with the National Institutes of Health (NIH), the
Association of American Medical Colleges (AAMC), and the American
Society of Clinical Oncology (ASCO).
DATES: Submit written or electronic information and comments by June 3,
2009.
ADDRESSES: You may submit comments by any of the following methods:
E-mail: [email protected]. Include ``IRB
Accountability RFI'' in the subject line.
Fax: 301-402-2071.
Mail/Hand Delivery/Courier [For paper, disk, or CD-ROM
submissions]: Julie Kaneshiro, OHRP, 1101 Wootton Parkway, Suite 200,
Rockville, MD 20852.
Comments received within the comment period, including any personal
information provided, will be made available to the public upon
request.
FOR FURTHER INFORMATION CONTACT: Julie Kaneshiro, OHRP, 1101 Wootton
Parkway, Suite 200, Rockville, MD 20852; 240-453-6900; e-mail
[email protected].
SUPPLEMENTARY INFORMATION:
I. Background
HHS, through OHRP, regulates research involving human subjects
conducted or supported by HHS in regulations codified at 45 CFR part
46. The HHS regulations at 45 CFR part 46 identify requirements that
pertain to several different entities, including the IRB and the
institution engaged in non-exempt human subjects research. The IRB is
an administrative body that takes the form of a board, committee, or
group, and is responsible for conducting initial and continuing review
of research involving human subjects. The IRB must have authority to
approve, require modification in (in order to secure approval), or
disapprove all research activities covered by the HHS regulations (45
CFR 46.109(a)). An IRB's primary purpose in reviewing research is to
ensure the protection of the rights and welfare of human research
subjects.
Requirements for an Assurance of Compliance
The HHS regulations for the protection of human subjects require
that each institution engaged in non-exempt human subjects research
conducted or supported by HHS provide a written assurance satisfactory
to the Secretary of Health and Human Services that it will comply with
the requirements of the HHS regulations (45 CFR 46.103(a)). OHRP
reviews and approves such assurances on behalf of HHS. The Federalwide
Assurance (FWA) is now the only type of assurance accepted and approved
by OHRP. An FWA commits the entire institution (including institutional
officials, IRBs designated in the assurance, research investigators,
and all other employees or agents) to compliance with the HHS
regulations whenever the institution is engaged in HHS-conducted or
[[Page 9579]]
-supported human subjects research. In addition, domestic institutions
may voluntarily extend their FWA to cover all human subjects research
at their institution regardless of the source of support for the
particular research activity.
Among other things, an institution's assurance of compliance must
designate all of the IRBs that the institution will rely upon for the
review of any research covered by its assurance (45 CFR 46.103(b)(2)).
For each designated IRB, a list of IRB members identified by name,
earned degrees, representative capacity, experience, and any employment
or other relationship with the institution must be submitted to OHRP
(45 CFR 46.103(b)(3)). The HHS regulations at 45 CFR part 46 provide an
institution with significant flexibility in designating the IRBs that
will review research under the institution's FWA. Options available to
the institution include:
Designating on its FWA one or more IRBs that are operated
by the institution (sometimes referred to as ``local'' or ``internal''
IRBs; hereafter referred to as ``internal IRBs''); and
Designating on its FWA one or more IRBs operated by other
institutions or commercial or independent IRBs (hereafter referred to
as ``external IRBs'').
As stated in the Terms of Assurance for the FWA (see http://www.hhs.gov/ohrp/humansubjects/assurance/filasurt.htm), for each
external IRB designated on an institution's FWA, an IRB Authorization
Agreement must be executed:
Any designation under this Assurance of another Institution's
IRB or an independent IRB must be documented by a written agreement
between the Institution and the IRB organization outlining their
relationship and include a commitment that the designated IRB will
adhere to the requirements of this Assurance. OHRP's sample IRB
Authorization Agreement may be used for such purpose or the two
organizations may develop their own agreement. This agreement should
be kept on file at both organizations and made available to OHRP
upon request.
OHRP provides an example of an IRB Authorization Agreement at
http://www.hhs.gov/ohrp/humansubjects/assurance/iprotsup.rtf. The
agreement may be written to cover one research project, or to cover
multiple research projects on a case-by-case basis, or to cover a class
of research projects. This agreement will sometimes include a
description of which regulatory requirements each party will be
responsible for; e.g., reporting unanticipated problems involving risks
to subjects or others (45 CFR 46.103(b)(5)) or the maintenance of IRB
records (45 CFR 46.115).
Requirements for IRB Registration
Before an IRB may be designated on an institution's FWA, the IRB
must be registered with OHRP. For more information on IRB registration
see http://www.hhs.gov/ohrp/assurances/.
OHRP has been operating a system of IRB registration since December
2000, which was initiated in response to a 1998 HHS Office of Inspector
General recommendation that all IRBs register with the Federal
government on a regular basis as part of an effort to develop a more
streamlined, coordinated, and probing means of assessing IRB
performance and to enhance the Federal government's ability to identify
and respond to emerging problems.
The OHRP IRB registration system was designed to collect
information required under the HHS human subjects protection
regulations at 45 CFR 46.103, as well as additional information that is
provided voluntarily by institutions or IRBs regarding the
accreditation status of the institution or IRB organization, the total
numbers of active research protocols reviewed by the IRB (including
protocols supported by other Federal departments or agencies) and the
nature of those protocols, and IRB staffing.
On July 6, 2004, OHRP published in the Federal Register a Notice of
Proposed Rulemaking (NPRM) seeking public comment on changes to the
current IRB registration system administered by OHRP (69 FR 40584).
OHRP proposed to amend the HHS human subjects protection regulations at
45 CFR part 46 by adding an additional subpart, entitled ``Registration
of Institutional Review Boards.'' Under the proposed new subpart, for
any IRB designated under an FWA that reviews human subjects research
conducted or supported by HHS, most of the information, including the
information that previously was provided on a voluntary basis, listed
on the current OHRP IRB registration form would have to be submitted to
OHRP. By requiring such information to be provided for all IRBs being
registered, OHRP's IRB registration requirements would become
substantially consistent with requirements for IRB registration that
were simultaneously proposed by FDA (69 FR 40556).
After taking into consideration the comments received during the
public comment period, OHRP and FDA issued separate final IRB
registration rules on January 15, 2009, that will become effective on
July 14, 2009 (74 FR 2399; 74 FR 2358). OHRP's and FDA's IRB
registration rules are compatible and largely consistent with one
another. Under these final rules there will be a single registration
system, accessible on the OHRP Web site, in which all IRBs that review
research conducted or supported by HHS or clinical investigations
regulated by FDA will need to be registered.
Enforcement Authority
Section 289 of the Public Health Service Act authorizes OHRP to, on
behalf of HHS, establish a compliance oversight process regarding
violations of the rights of human subjects of research conducted or
supported by HHS. Pursuant to this authority, OHRP may receive reports
of such violations and take appropriate action.
OHRP also derives compliance oversight authority from the
previously discussed provisions of the HHS regulations at 45 CFR
46.103(a) and its implementation of the FWA.
Unlike the FDA regulations pertaining to IRBs, which explicitly
include compliance oversight provisions at subpart E of 21 CFR part 56,
the HHS regulations at 45 CFR part 46 do not include provisions
specifically addressing IRB or IORG compliance with the regulatory
requirements.
II. History of OHRP Compliance Oversight and the Changing Research
Environment
Historically, OHRP (and its predecessor office, the Office for
Protection from Research Risks) has only enforced compliance with 45
CFR part 46 through the institutions that were engaged in human
subjects research. This has been the case even in circumstances when
the regulatory violation was directly related to the responsibilities
of an external IRB that was designated on the engaged institution's
assurance of compliance with OHRP. Therefore, when OHRP received an
allegation or indication of a regulatory violation on the part of an
external IRB related to research to which the HHS regulations apply,
OHRP has directed its compliance oversight evaluations and enforcement
actions to the relevant FWA-holding institutions, not the external IRB
or IORG at issue. When the HHS regulations related to IRB review last
underwent a substantive revision on June 18, 1991 (56 FR 28003), few
institutions were designating external IRBs to review research
conducted under their assurances of compliance, in part because single
site studies were more common than they are today, and it was more
common for HHS-supported
[[Page 9580]]
research to be conducted by large academic medical centers that had
their own internal IRBs. Therefore, there was no perceived need to hold
IRBs or IORGs directly accountable for meeting any of the requirements
of the HHS regulations at 45 CFR part 46. However, as HHS support for
multi-site studies has increased, and previously non-traditional
research settings, such as community hospitals and medical clinics,
have become frequent research sites, the research community has looked
for ways to make IRB review more effective and efficient.
III. Current Regulatory Flexibilities for IRB Review Arrangements
The regulations offer institutions significant flexibility to
implement a variety of cooperative review arrangements as permitted
under 45 CFR 46.114. In addition, this flexibility is facilitated by
the ability of institutions to designate external IRBs on their FWAs
that will be responsible for the review of one or more research studies
in which the institution will be engaged. These regulatory
flexibilities are intended to reduce administrative burden without
diminishing human subject protections. For example, two or more
institutions engaged in the same multi-center research project can
designate the same IRB (e.g., an IRB operated by one of the
institutions engaged in the project) on their FWAs to review that
research project. Similarly, institutions that do not have an internal
IRB (for example, because they conduct little human subjects research)
may designate an external IRB on their FWAs to review one or more
research studies. Another IRB review model permitted under 45 CFR part
46 is for an institution to designate more than one IRB on its FWA to
share authority and responsibility for the review of certain research
studies. For example, the facilitated review model developed by the
National Cancer Institute utilizes a central IRB, as well as review by
another IRB--typically an internal IRB operated by the institution
engaged in the research--that is responsible for considering issues
related to the local context in which the research will be conducted.
These regulatory flexibilities under 45 CFR part 46, that permit
institutions to implement a variety of IRB review arrangements, are
intended to reduce administrative burdens such as the time associated
with IRB review for multi-site studies, the time devoted by IRB staff
and investigators to duplicative IRB review, and the time and personnel
costs associated with operating an IRB for those institutions that
choose not to establish an internal IRB.
Despite the regulatory flexibility to implement a wide range of IRB
review arrangements, OHRP has become aware that some institutions
remain reluctant to designate external IRBs on their FWAs and/or rely
upon cooperative IRB review arrangements.
IV. OHRP Co-Sponsored Meetings on Alternative IRB Models
OHRP's practice of holding an institution engaged in a human
subjects research study accountable for noncompliance on the part of an
external IRB that was designated on the institution's FWA and was
responsible for reviewing the research was identified as one of the key
factors influencing institutions' decisions about this issue by
participants in two meetings on alternative IRB models that OHRP co-
sponsored in November 2005 and November 2006. OHRP co-sponsored these
meetings along with NIH, AAMC, and ASCO, in response to a suggestion
made by SACHRP in the fall of 2004 that OHRP further explore issues
associated with the use of alternatives to local IRBs. Reports
summarizing the findings of these two meetings can be found at http://www.dhhs.gov/ohrp/sachrp/documents/AltModIRB.pdf and http://www.aamc.org/research/irbreview/irbconf06rpt.pdf. Participants in the
2005 and 2006 meetings included individuals from a variety of
perspectives, including IRB chairs, academic investigators, community-
based researchers, attorneys, patients, ethicists, industry officials
and senior university and medical school research administrators. While
other factors were also identified as contributing to institutions'
reluctance to adopt alternatives to the internal IRB review model, it
is OHRP's understanding from participants in this meeting, as well as
others in the community, that concerns related to regulatory liability
are a significant consideration. Namely, one of the main factors
identified as contributing to institutions' reluctance to rely on an
external IRB is OHRP's current practice of enforcing compliance with 45
CFR part 46 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. Given
this, OHRP believes that expanding its enforcement authority to include
IRBs and IORGs directly may make institutions more likely to designate
external IRBs on their FWAs and/or enter into cooperative IRB review
arrangements.
V. Possible Administrative Actions for Noncompliance by IRBs or IORGs
If HHS were to implement a regulation that would enable OHRP to
hold IRBs and IORGs directly accountable for meeting certain regulatory
requirements of 45 CFR part 46, OHRP envisions that it would generally
only exercise this regulatory option when the IRB at issue was external
to the institution engaged in the human subjects research, and was
designated on the institution's FWA to review the research. In
circumstances when the IRB at issue was internal to the institution
engaged in the human subjects research, OHRP expects that it would
continue to enforce compliance with 45 CFR part 46 through the engaged
institution.
However, when the possible regulatory noncompliance at issue was
the responsibility of an IRB external to the institution engaged in the
human subjects research, and the external IRB was designated on the
institution's FWA to review the research, OHRP generally would expect
to enforce compliance with 45 CFR part 46 directly with the external
IRB, and not the FWA-holding institution. OHRP contemplates a number of
administrative actions that HHS could take in response to a finding of
noncompliance with 45 CFR part 46 by an external IRB designated on an
institution's FWA. Depending on the nature and scope of the IRB's or
IORG's noncompliance, OHRP could, for example, require that the IRB or
IORG implement certain corrective actions, restrict or impose
conditions on the IRB's registration with OHRP, or suspend the IRB's
registration with OHRP which would prohibit the IRB from being
designated on any institution's FWA.
VI. Identifying Responsibilities of the IRB/IORG and FWA-Holding
Institution
In considering how HHS would implement a regulation that would
enable OHRP to hold IRBs and IORGs directly accountable for meeting
certain regulatory requirements of 45 CFR part 46, OHRP has begun the
process of identifying which entities might be responsible for
fulfilling the various regulatory requirements. Some of the regulatory
requirements seem to fall uniquely to either the IRB/IORG or the FWA-
holding institution, and others seem to be requirements that could be
carried out by either the IRB/IORG or the FWA-holding institution. OHRP
envisions that some form of agreement between the IRB/IORG and the FWA-
holding institution would determine which entity would be responsible
for
[[Page 9581]]
fulfilling the regulatory requirements that could be carried out by
either the IRB/IORG or the FWA-holding institution. In an attempt to
facilitate public comment on this request for information regarding IRB
accountability, OHRP has made a preliminary attempt to group the
regulatory requirements into the following three categories: (1)
Responsibilities that may be unique to IRBs and IORGs; (2)
responsibilities that may be unique to institutions engaged in human
subjects research; and (3) responsibilities that may be fulfilled by
either IRBs/IORGs or institutions engaged in human subjects research.
OHRP considered whether there are any regulatory requirements that
are inherently shared by both the IRB/IORG and the FWA-holding
institution, but did not identify any requirements that seemed to fall
into this category. Section VII of this notice includes a question that
specifically seeks public comment on this issue.
The categorization below is in no way intended to be definitive or
complete, but rather a basis for public comment.
Responsibilities That May Be Unique to IRBs and IORGs
The provisions regarding IRB membership and qualifications
necessary to promote complete and adequate review of the human subjects
research conducted by the institution for which the IRB was designated
on an institution's assurance of compliance with OHRP (Sec. 46.107).
The provision that the IRB follow written procedures in
the same detail as described in 45 CFR 46.103(b)(4) and to the extent
required by 45 CFR 46.103(b)(5) (Sec. 108(a)).
The provision that except when an expedited review
procedure is used (see Sec. 46.110), the IRB 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. 46.108(b)).
The provision that an IRB shall review and approve,
require modifications in (to secure approval), or disapprove all
research activities covered by 45 CFR part 46, for which the IRB was
designated on an institution's assurance of compliance with OHRP (Sec.
46.109(a)).
The provision that an IRB shall require that information
given to subjects as part of informed consent is in accordance with
Sec. 46.116. The IRB may require that information, in addition to that
specifically mentioned in Sec. 46.116, 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 (Sec. 46.109(b)).
The provision that an IRB shall require documentation of
informed consent or may waive documentation in accordance with Sec.
46.117 (Sec. 46.109(c)).
The provision that 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 (Sec. 46.109(d)).
The provision that an IRB shall conduct continuing review
of research covered by 45 CFR part 46, at intervals appropriate to the
degree of risk, but not less than once per year (Sec. 46.109(e)).
The provision related to expedited review procedures for
certain kinds of research involving no more than minimal risk, and for
minor changes in approved research (Sec. 46.110).
The provision that identifies the criteria for IRB
approval of research (Sec. 46.111).
The provisions that permit an IRB to approve a consent
procedure which does not include, or which alters some or all of the
elements of informed consent set forth in Sec. 46.116, or waive the
requirements to obtain informed consent provided the IRB finds and
documents that specified criteria have been met (Sec. 46.116(c) and
(d)).
The provisions that require informed consent to be
documented by use of a written consent form approved by the IRB and
signed by the subject or the subject's legally authorized
representative, unless the IRB finds that specified criteria permitting
the waiver of documentation of informed consent have been met (Sec.
46.117).
Responsibilities That May Be Unique to Institutions Engaged in Human
Subjects Research
The provision that institutions engaged in HHS-supported
human subjects research must submit an FWA to OHRP for approval and
comply with the requirements imposed as part of the FWA, including
among other things, the designation of one or more IRBs on the
institution's FWA that have been registered with OHRP (Sec. 46.103).
The requirement that before implementing a change to an
IRB-approved research study, an investigator must obtain IRB approval
for the change, unless the change is designed to eliminate an apparent
immediate hazard to subjects (Sec. 46.103(b)(4)).
The requirement that an investigator must obtain
continuing IRB review of ongoing non-exempt human subjects research
prior to the expiration date of the current IRB approval (Sec.
46.103(b)(4)).
The requirement for the prompt reporting to the IRB of any
unanticipated problems involving risks to subjects or others or any
serious or continuing noncompliance with 45 CFR part 46 or the
requirements or determinations of the IRB (Sec. 46.103(b)(5)).
The requirement that an investigator must obtain IRB
review and approval before beginning any non-exempt human subjects
research (Sec. 46.109(a)).
The provision that the IRB must have authority to approve,
require modifications in (to secure approval), or disapprove all
research activities for which the IRB was designated on an
institution's assurance of compliance with OHRP (Sec. 46.109(a)).
The provision that the IRB must have authority to observe
or have a third party observe the consent process and the research for
all research activities for which the IRB was designated on an
institution's assurance of compliance with OHRP (Sec. 46.109(e)).
The provision that research covered by 45 CFR part 46 that
has been approved by an IRB may be subject to further appropriate
review and approval or disapproval by officials of the institution.
However, these officials may not approve the research if it has not
been approved by an IRB (Sec. 46.112).
The provision that the IRB must 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 for all research activities for
which the IRB was designated on an institution's assurance of
compliance with OHRP (Sec. 46.113).
The requirement that except as provided elsewhere in 45
CFR part 46 no investigator may involve a human being as a subject in
research covered by 45 CFR part 46 unless the investigator has obtained
and documented the legally effective informed consent of the subject or
the subject's legally authorized representative (Sec. 46.116 and Sec.
46.117).
The requirement that investigators give a copy of the
informed consent document to each research subject or
[[Page 9582]]
the subject's legally authorized representative, and keep the signed
original or a copy of it for their records, unless the IRB finds that
specified criteria permitting the waiver of documentation of informed
consent have been met (Sec. 46.117; Sec. 46.115(b)).
Responsibilities That May Be Fulfilled by Either IRBs/IORGs or
Institutions Engaged in Human Subjects Research
Determining the applicability of the HHS regulations at 45
CFR part 46 (e.g., the exemptions at 46.101(b)).
Developing written IRB procedures which the IRB will
follow:
(1) For conducting its initial and continuing review of research
and for reporting its findings and actions to the investigator and the
institution;
(2) For 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
(3) For 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 (Sec.
46.103(b)(4)).
Developing written IRB procedures for ensuring the prompt
reporting to the IRB, appropriate institutional officials, and the
Department or Agency head of:
(1) Any unanticipated problems involving risks to subjects or
others or any serious or continuing noncompliance with 45 CFR part 46
or the requirements or determinations of the IRB; and
(2) Any suspension or termination of IRB approval (Sec.
46.103(b)(5).
Promptly reporting to the appropriate institutional
officials and the Department or Agency head:
(1) Any unanticipated problems involving risks to subjects or
others or any serious or continuing noncompliance with 45 CFR part 46
or the requirements or determinations of the IRB; and
(2) Any suspension or termination of IRB approval, including a
statement of the reasons for the IRB's actions (Sec. 46.103(b)(5);
Sec. 46.113).
Promptly reporting to the investigator any suspension or
termination of approval by the IRB, including a statement of the
reasons for the IRB's actions (Sec. 46.113).
Fulfilling the documentation and recordkeeping
requirements associated with IRB activities (Sec. 46.115).
VII. Request for Information and Comments
OHRP is seeking information and comments from the public about
whether OHRP should pursue an NPRM to enable OHRP to hold IRBs and
IORGs directly accountable for meeting certain regulatory requirements
of the HHS regulations for the protection of human subjects at 45 CFR
part 46. OHRP specifically seeks information and comments on the
following issues; comments should also include a reference to the
specific numbered question being addressed:
1. Is there sufficient need for HHS to pursue a regulatory change
to enable OHRP to hold IRBs and IORGs directly accountable for meeting
certain requirements of the HHS regulations at 45 CFR part 46? Please
explain your response.
2. Would the proposed regulatory change reduce concerns about
regulatory liability as a barrier to the use of external IRBs and
contribute to an increase in collaborative IRB review arrangements?
3. Are there other approaches and strategies that would decrease
concern about regulatory liability and increase collaborative IRB
review arrangements?
4. If HHS were to issue a regulation that would enable OHRP to hold
IRBs and IORGs directly accountable for meeting certain requirements of
the HHS regulations at 45 CFR part 46, would this have the unintended
effect of making institutions or IORGs less willing to have their IRBs
designated as external IRBs on other institutions' FWAs? If so, would
there still be sufficient benefit for HHS to pursue a regulatory change
to enable OHRP to hold IRBs and IORGs directly accountable for meeting
certain requirements of the HHS regulations? Are there other possible
unintended effects of the proposed regulatory change? Please explain
your responses.
5. If HHS pursues a regulatory change to enable OHRP to hold IRBs
and IORGs directly accountable for meeting certain requirements of the
HHS regulations at 45 CFR part 46, what kinds of administrative actions
would be appropriate for OHRP to take against IRBs that are found to be
out of compliance with 45 CFR part 46? For a description of some of the
corrective actions that OHRP has required when it has been determined
that an institution was not in compliance with 45 CFR part 46, see
OHRP's guidance document entitled, ``OHRP's Compliance Oversight
Procedures for Evaluating Institutions'' at http://www.dhhs.gov/ohrp/compliance/ohrpcomp.pdf.
6. As described in Section VI of this notice, in order to
facilitate public comment, OHRP has made a preliminary attempt to group
some of the regulatory requirements under 45 CFR part 46 into the
following three categories: (1) Responsibilities that may be unique to
IRBs and IORGs; (2) responsibilities that may be unique to institutions
engaged in human subjects research; and (3) responsibilities that may
be fulfilled by either IRBs/IORGs or institutions engaged in human
subjects research.
6a. Are these categories appropriate? If not, what other categories
should there be?
6b. Is there a fourth category of responsibilities that are
inherently shared by both the IRB/IORG and the FWA-holding institution?
If so, please provide examples of such shared responsibilities.
6c. Are the regulatory provisions identified under each of the
categories appropriate? If not, which regulatory provisions should be
re-categorized, removed, or added?
6d. For institutions that have relied upon joint IRB review
arrangements in the past, how have the regulatory requirements been
divided or shared by the IRB/IORG and the institution engaged in the
human subjects research? We would welcome examples or descriptions of
such agreements between IRBs/IORGs and institutions engaged in human
subjects research that describe their respective responsibilities.
7. With regard to the responsibilities that may be fulfilled by
either IRBs or institutions, the IRB Authorization Agreement between an
external IRB and an FWA-holding institution is often used to clarify
which entity will be responsible for carrying out these regulatory
requirements.
7a. If a regulatory change to 45 CFR part 46 is pursued, should
OHRP use the IRB Authorization Agreement or other forms of agreement,
if they exist (e.g., contract or memorandum of understanding) to inform
its compliance oversight evaluations about which entity should be held
responsible for fulfilling regulatory requirements that could be met by
either an external IRB or the FWA-holding institution?
7b. If a regulatory change to 45 CFR part 46 is pursued, should
there be new provisions that require specific content for IRB
Authorization Agreements or for other forms of agreements between
external IRBs and FWA-holding
[[Page 9583]]
institutions? If so, what types of content should be required?
7c. If a regulatory change to 45 CFR part 46 is pursued, should the
regulation describe which regulatory requirements would need to be met
by external IRBs and which regulatory requirements would need to be met
by institutions engaged in the research?
Dated: February 27, 2009.
Jerry Menikoff,
Director, Office for Human Research Protections.
[FR Doc. E9-4628 Filed 3-4-09; 8:45 am]
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