[Federal Register Volume 74, Number 214 (Friday, November 6, 2009)]
[Notices]
[Pages 57487-57490]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-26828]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Draft Guidance on Institutional Review Board Continuing Review of
Research
AGENCY: Office for Human Research Protections, Office of Public Health
and Science, Office of the Secretary, Department of Health and Human
Services.
ACTION: Notice.
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SUMMARY: The Office for Human Research Protections (OHRP), Office of
Public Health and Science, is announcing the availability of a draft
guidance document entitled, ``Guidance on IRB Continuing Review of
Research,'' and is seeking comment on the draft guidance. The draft
guidance document, when finalized, will represent OHRP's current
thinking on this topic and will supersede OHRP's January 15, 2007
guidance document entitled ``Guidance on Continuing Review,'' available
at http://www.hhs.gov/ohrp/humansubjects/guidance/contrev0107.htm. The
draft document, which is available on the OHRP Web site at http://www.hhs.gov/ohrp/requests/, is intended primarily for institutional
review boards (IRBs), investigators, Department of Health and Human
Services (HHS) funding agencies, and others that may be responsible for
the review, conduct, or oversight of human subject research conducted
or supported by HHS. OHRP will consider comments received before
issuing the final guidance document.
DATES: Submit written comments by January 5, 2010.
ADDRESSES: Submit written requests for single copies of the draft
guidance document entitled, ``Guidance on IRB Continuing Review of
Research,'' to the Division of Policy and Assurances, Office for Human
Research Protections, 1101 Wootton Parkway, Suite 200, Rockville, MD
20852. Send one self-addressed adhesive label to assist that office in
processing your request, or fax your request to 301-402-2071. See the
SUPPLEMENTARY INFORMATION section for information on electronic access
to the draft guidance document.
You may submit comments, identified by docket ID number HHS-OPHS-
2009-0016, 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 the ``Submit a
Comment'' action and follow the instructions.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
submissions]: Michael A. Carome, M.D., Captain, U.S. Public Health
Service, 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: Michael A. Carome, M.D., Captain, U.S.
Public Health Service, OHRP, 1101 Wootton Parkway, Suite 200,
Rockville, MD 20852, 240-453-6900; e-mail [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
A. Overview
OHRP is announcing the availability of a draft guidance document
entitled, ``Guidance on IRB Continuing Review of Research.'' The draft
guidance document, when finalized, will represent OHRP's current
thinking on this topic and will supersede OHRP's January 15, 2007
guidance document entitled ``Guidance on Continuing Review,'' available
at http://www.hhs.gov/ohrp/humansubjects/guidance/contrev0107.htm. The
draft document is intended primarily for IRBs, investigators, HHS
funding agencies, and others that may be responsible for the review,
conduct, or oversight of human subject research conducted or supported
by HHS.
To enhance human subject protections and reduce regulatory burden,
OHRP and the Food and Drug Administration have been actively working to
harmonize the agencies' regulatory requirements and guidance for human
subjects research. The draft guidance document was developed as a part
of these efforts.
The guidance document would apply to non-exempt human subjects
research conducted or supported by HHS. It provides guidance on the HHS
regulations for the protection of human research subjects at 45 CFR
part 46 related to IRB continuing review of research. In particular,
the guidance addresses the following major topics:
(1) Key IRB Considerations when Evaluating Research Undergoing
Continuing Review;
(2) Process for Conducting Continuing Review;
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(3) Additional Considerations for Continuing Review of Multicenter
Research Projects;
(4) When Expedited Review Procedures may be Used by an IRB for
Continuing Review;
(5) Determining the Frequency of Continuing Review;
(6) Determining the Effective Date of Initial IRB Approval and the
Dates for Continuing Review;
(7) Lapses in IRB Approval;
(8) Communicating the IRB's Continuing Review Determination to
Investigators and the Institution;
(9) Suspension or Termination of IRB Approval of Research or
Disapproval of Research at the Time of Continuing Review;
(10) Identifying the Point When Continuing Review is No Longer
Necessary; and
(11) Continuing Review is Not Required for Exempt Human Subjects
Research Projects.
B. Response to the Secretary's Advisory Committee on Human Research
Protections' (SACHRP's) Recommendations Regarding OHRP's Current
Guidance on Continuing Review
In a March 14, 2007 letter, SACHRP transmitted to the Secretary of
Health and Human Services 14 recommendations regarding continuing
review, 13 of which called for changes in OHRP's current guidance on
continuing review. These recommendations were the primary impetus for
OHRP to draft an updated guidance document on IRB continuing review.
The following discussion describes OHRP's response to these SACHRP
recommendations and identifies the section(s) of the draft guidance
document that address specific recommendations.
(1) SACHRP Recommendation: OHRP should clarify its guidance on the
required duration of continuing review. Continuing review may end when
all research interventions and interactions with subjects are over and
data collection for research purposes is complete, as described in the
approved study plan/protocol, at the research site for which the IRB
has oversight. The IRB must have reviewed and approved the
investigator's plan for data analysis and the safeguards in place for
confidentiality protections. The investigator still retains the
responsibility to notify former subjects and the IRB if subsequent
analyses and/or new information raise concerns about rights, safety,
and welfare of human subjects.
OHRP's Response: Given (a) OHRP's current interpretation of what it
means to obtain identifiable private information; (b) category (8)(c)
on the list of categories of research that may be reviewed by the IRB
through an expedited review procedure; and (c) the importance of
continuing to require the prompt reporting of unanticipated problems
involving risks to subjects or others to the IRB, appropriate
institutional officials, and OHRP that may occur during the data
analysis phase of a research study, OHRP believes that continuing
review should continue at least annually as long as the analysis of
data that includes individually identifiable private information, as
described in the IRB-approved protocol, is ongoing. However, as
discussed in section E.2 of the draft guidance (under the sub-heading
``Expedited review category (8)(c) and data analysis'') this continuing
review can be expedited and done in a way that results in little, if
any, burden. The draft guidance also explains that for a multicenter
research project, only the institution engaged in the ongoing data
analysis activities (e.g., the institution operating the coordinating
center or statistical center for the research project) needs to ensure
that continuing review of the research by an IRB designated under the
institution's FWA occurs at least annually. Finally, the draft guidance
in section K clarifies that when data analysis activities for a
research study progress to the point when they no longer involve
analysis of identifiable private information, further continuing review
of the research is no longer required.
(2) SACHRP Recommendation: OHRP should revise its interpretation
and develop new guidance to (a) define simplified criteria and the
expectations for the content of continuing review based upon current
risk level; and (b) to permit IRBs to develop, within their written
procedures, policies and procedures for the selective application of
section 46.111 to continuing review.
OHRP's Response: OHRP has retained its interpretation that the
criteria for IRB approval of research at the time of continuing review
are the criteria under HHS regulations at 45 CFR 46.111, and when
applicable, the criteria under subparts B, C, and D of 45 CFR part 46.
However, the draft guidance explains in section B.1 that at the time of
continuing review, the IRB should start with the presumption that the
research, as previously approved, does satisfy these criteria and
should focus on whether there is any new information provided by the
investigator that would alter the prior determinations of the IRB. The
guidance then recommends in sections B.2-B.5 that, when conducting
continuing review and evaluating whether research continues to satisfy
the criteria for IRB approval of research, IRBs should pay particular
attention to the following four aspects of the research: (1) Risk
assessment and monitoring; (2) adequacy of the process for obtaining
informed consent; (3) investigator and institutional issues; and (4)
research progress.
(3) SACHRP Recommendation: OHRP should modify its interpretation of
expedited review category (8)(b) so that expedited review is permitted
if no additional risks have been identified at any research sites and
no interventions or other study activities have occurred at the IRB's
research site since the preceding review. Guidance should be revised to
reflect this interpretation.
OHRP's Response: Implementation of this recommendation would
require revision of the expedited review list. Therefore, this
recommendation cannot be addressed through revision of OHRP's guidance
on IRB continuing review.
(4) SACHRP Recommendation: OHRP should revise its current guidance
to give more examples of when continuing review is not necessary and
when expedited review category (9) may be used.
OHRP's Response: OHRP agrees with this recommendation. Section E.3
of the draft guidance includes two examples of research studies that
would be eligible for continuing review under an expedited review
procedure under category (9); one involving research that includes
chest x-ray procedures, and another involving research that includes
procedures for collection of blood at a frequency which exceeds the
frequency described in expedited review category (2). OHRP invites the
public to provide suggestions of other examples.
Section K of the draft guidance provides guidance on when
continuing review of a research study would no longer be necessary.
(5) SACHRP Recommendation: OHRP should revise its guidance to
clarify an expectation that the investigator is responsible for the
review and interpretation of ``recent and relevant'' literature for IRB
evaluation. Guidance should clarify that it is not an IRB
responsibility to perform a review of the scientific literature.
OHRP's Response: OHRP agrees with this recommendation. The draft
guidance in section C.4 includes an explicit statement that OHRP does
not expect the IRB to perform an independent review of the relevant
scientific literature related to a particular research project
undergoing continuing review and that this
[[Page 57489]]
responsibility rests with the investigators and any monitoring entity
for the research.
(6) SACHRP Recommendation: OHRP should revise its guidance to
emphasize that once a research protocol is determined to be exempt, and
all subsequent research activities continue to meet exemption criteria,
there is no regulatory requirement for ongoing review.
OHRP's Response: OHRP agrees with this recommendation. The draft
guidance in section L advises that once the determination has been made
that a research project is exempt, no continuing review of the project
by the IRB is required under the HHS regulations at 45 CFR part 46.
(7) SACHRP Recommendation: OHRP should prepare simplified, unified,
and practical guidance for continuing review that focuses on the
substance of review.
OHRP's Response: OHRP agrees with this recommendation. The draft
guidance document in its entirety represents an attempt to consolidate
in one guidance document all OHRP guidance regarding continuing review.
In preparing the draft guidance on continuing review, content was taken
from the following documents: (a) The January 15, 2007 Guidance on
Continuing Review; (b) the January 15, 2007 Guidance on Written IRB
Procedures; (c) the January 15, 2007 Guidance on Reviewing and
Reporting Unanticipated Problems Involving Risks to Subjects or Others
and Adverse Events; (d) OHRP's Frequently Asked Questions on
Investigator Responsibilities; and (e) the August 11, 2003 Guidance on
Expedited Review. Section B of the draft guidance focuses on the
substance of continuing review through its discussion of key IRB
considerations when reviewing research undergoing continuing review.
Section C of the draft guidance focuses on the process for conducting
IRB review and provides guidelines for facilitating and simplifying
this process.
(8) SACHRP Recommendation: OHRP should revise its guidance to
reflect that the final IRB approval of a study ``sets the clock'' for
continuing review. For multi-site reviews, this may differ by site.
OHRP's Response: OHRP agrees with this recommendation with respect
to setting the date for the first continuing review of a research study
that was initially reviewed and approved by the IRB at a convened
meeting. The draft guidance in section G clarifies that instead of the
first continuing review being required within one year of the convened
meeting at which the initial approval was granted, it must occur within
one year of the date on which any changes or clarifications requested
by the IRB at its convened meeting have been reviewed and accepted as
satisfactory by the IRB chairperson (or other individual(s) designated
by the IRB at the time of the convened IRB meeting). OHRP notes that
adoption of this recommendation represents a change to OHRP's long-
standing policy position on this issue.
(9) SACHRP Recommendation: OHRP should revise its ``30-day rule''
to remove unnecessary restrictions on IRBs in scheduling continuing
reviews. If a defined time window is deemed necessary, 60 days would be
more appropriate.
OHRP's Response: OHRP has retained its current position on this
issue (see section G.3 of the draft guidance).
(10) SACHRP Recommendation: OHRP should modify its guidance on
continuing review so that, when the study has been reviewed by the IRB
(at a convened meeting or through an expedited process, as appropriate)
and the IRB finds that there are no substantive concerns in terms of
the risk-benefit relationship, informed consent, or other key
protections, suspension of all research activity is not required when
the expiration date passes, provided that IRB review is completed
within 30 days past the expiration date.
OHRP's Response: OHRP has addressed this recommendation through its
discussion of conditional approval by the IRB in section C.9 of the
draft guidance on continuing review and its new draft Guidance on IRB
Approval of Research with Conditions that is also being made available
for public review and comment, as noted in another notice of
availability published in this same issue of the Federal Register.
(11) SACHRP Recommendation: Regarding the issue of continued
participation of already enrolled subjects in research during temporary
lapses in IRB approval, wording in current OHRP guidance that refers to
``individual requests'' should be revised to clarify that approval of a
general request for all research subjects to continue in the research
during the review process is acceptable.
OHRP's Response: OHRP agrees with this recommendation. The draft
guidance in section H advises that the determination regarding whether
it is in the best interests of already enrolled subjects to continue to
participate in the research after IRB approval has expired may be made
for all enrolled subjects as a group or for each individual subject.
(12) SACHRP Recommendation: OHRP guidance on continuing review
should be revised to state that a ``protocol summary'' may or may not
be a separate document; and that combination of information sources,
such as consent forms and the continuing review application, may
appropriately constitute a ``summary'' for the IRB members.
OHRP's Response: OHRP agrees with this recommendation. The draft
guidance in section C.4 clarifies that a project summary could be
included as part of a continuing review progress report, provided as a
separate document, or addressed by referencing other documents made
available to the IRB, including the informed consent document.
(13) SACHRP Recommendation: OHRP should clarify its guidance to
state that qualified IRB staff may act as a consultant to the IRB and
accomplish the review of the full study protocol.
OHRP's Response: OHRP agrees with this recommendation in part. OHRP
believes that IRB staff who are not IRB members can carry out review
activities of the IRB file to facilitate the review conducted by IRB
members at the time of continuing review. However, determinations that
the IRB must make under the regulations at 45 CFR 46.111 and, when
applicable, subparts B, C, and D, must be made by the IRB members, and
individuals who are not IRB members may not approve research on behalf
of the IRB. The draft guidance in section C.7 discusses the involvement
of IRB staff in preliminary review of IRB records as part of the
continuing review process.
C. Summary of Additional Key Changes and New Content
(1) The draft guidance does not include a reference to
``substantive and meaningful continuing review'' that is found in
OHRP's current guidance on continuing review. Instead, the new draft
guidance has been expanded to include a section on key IRB
considerations when evaluating research undergoing continuing review
(see section B) and to provide more details regarding regulatory
requirements and recommendations for the process for conducting
continuing review (see section C).
(2) The draft guidance recommends that IRBs act and vote on
research studies individually. It further clarifies that if an IRB
adopts a procedure under which the IRB votes on groups of studies
undergoing continuing review, such a procedure must provide IRB members
with the ability to vote ``yes'' on some studies, ``no'' on others, and
abstain on others.
[[Page 57490]]
(3) The draft guidance provides new guidance on the involvement of
IRB staff, regardless of whether they are IRB members, in preliminary
reviews of continuing review documents and IRB files in order to
facilitate the continuing review of research by the IRB (see section
C.7).
(4) The draft guidance describes how continuing review of research
at convened meetings can be accomplished in an efficient and timely
manner (see section C.8).
(5) The draft guidance discusses the concept of conditional IRB
approval in the context of continuing review (see section C.9).
(6) The draft guidance discusses issues unique to continuing IRB
review of multicenter research studies (see section D).
(7) The draft guidance clarifies the point in time when continuing
review is no longer necessary (see section K).
II. Electronic Access
The draft guidance document is available on OHRP's Web site at
http://www.hhs.gov/ohrp/requests/.
III. Request for Comments
OHRP requests comments on its draft guidance document. OHRP will
consider all comments before issuing a final guidance document.
Dated: November 3, 2009.
Jerry Menikoff,
Director, Office for Human Research Protections.
[FR Doc. E9-26828 Filed 11-5-09; 8:45 am]
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