Section K of the draft guidance provides guidance on when continuing review of a research study would no longer be necessary.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 The draft guidance in section C.4 includes an explicit statement that OHRP does not expect the IRB to perform an independent review of the relevant scientific literature related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 thisresponsibility 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 The draft guidance in section L advises that once the determination has been made that a research project is exempt, no continuing review of the project by the IRB is required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 The draft guidance document in its entirety represents an attempt to consolidate in one guidance document all OHRP guidance regarding continuing review. In preparing the draft guidance on continuing review, content was taken from the following documents: (a) The January 15, 2007 Guidance on Continuing Review; (b) the January 15, 2007 Guidance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 Section B of the draft guidance focuses on the substance of continuing review through its discussion of key IRB considerations when reviewing research undergoing continuing review. Section C of the draft guidance focuses on the process for conducting IRB review and provides guidelines for facilitating and simplifying this process.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 (seesection 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 draftGuidance on IRB Approval of Research with Conditionsthat is also being made available for public review and comment, as noted in another notice of availability published in this same issue of theFederal 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 (seesection B) and to provide more details regarding regulatory requirements and recommendations for the process for conducting continuing review (seesection 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.
(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 (seesection C.7).
(4) The draft guidance describes how continuing review of research at convened meetings can be accomplished in an efficient and timely manner (seesection C.8).
(5) The draft guidance discusses the concept of conditional IRB approval in the context of continuing review (seesection C.9).
(6) The draft guidance discusses issues unique to continuing IRB review of multicenter research studies (seesection D).
(7) The draft guidance clarifies the point in time when continuing review is no longer necessary (seesection K).
II. Electronic Access
The draft guidance document is available on OHRP's Web site athttp://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.
Director, Office for Human Research Protections.