[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Draft Guidance on Institutional Review Board Continuing Review of 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Public Health and Science, is announcing the availability of a draft 
guidance document entitled, ``Guidance on IRB Continuing Review of 
Research,'' and is seeking comment on the draft guidance. The draft 
guidance document, when finalized, will represent OHRP's current 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ADDRESSES: Submit written requests for single copies of the draft 
guidance document entitled, ``Guidance on IRB Continuing Review of 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to the draft guidance document.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.

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    (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]
BILLING CODE 4150-36-P