1. Secretary’s Advisory Committee on Human Subjects Protections (SACHRP) Summary of Responses on: Advanced Notice of Proposed Rulemaking (ANPRM) on Holding Institutional Review Boards Directly Accountable Julie Kaneshiro Policy Team Leader Division of Policy and Assurances July 21, 2009

2. Background SACHRP recommendation Current regulatory flexibility

3. “OHRP, NIH, and FDA should consider holding a workshop focused on central IRB review mechanisms and that SACHRP use the workshop experience and other processes as a means of gathering information and moving forward toward future committee action.” SACHRP Recommendation (Fall, 2004)

4. Meetings on Alternative IRB Models OHRP co-sponsored meetings on alternative IRB models in November 2005 and November 2006 Other sponsors were NIH, the Association of American Medical Colleges, and the American Society of Clinical Oncology

5. Meetings on Alternative IRB Models Concluded: Despite existing regulatory flexibilities some institutions remain reluctant to designate external IRBs and rely on cooperative review arrangements.

6. Meetings on Alternative IRB Models A key factor: OHRP currently holds institution engaged in human subjects research study accountable for noncompliance on the part of the external IRB designated on FWA to review the research.

7. Current Regulatory Flexibility Cooperative review arrangements for multi-site research (45 CFR 46.114):  Joint IRB review  Facilitated IRB review  Reliance on external IRB

8. Current Regulatory Flexibility Designating IRBs on an FWA:  Internal IRB  External IRB - IRB of another institution - Independent or commercial IRB  Internal and external IRB  IRB composed of members from both inside and outside of the institution

9. OHRP Proposal to Hold IRBs Directly Accountable March 5, 2009, published an ANPRM Asked whether OHRP should revise 45 CFR part 46 to enable HHS to hold IRBs and IRB organizations (IORGs) directly accountable for compliance Comments due by June 3, 2009

10. Comments Received 30 comments received 13 comments were “joint” (e.g., Consortium of Independent Review Boards, Public Responsibility in Medicine and Research, Association of American Medical Colleges, Council on Governmental Relations, Pharmaceutical Research and Manufacturers of America) Distributed, as follows: -- 9 from universities/IRBs/investigators -- 11 from non-governmental organizations, private sector -- 10 from individuals

11. Key Question Asked : Classifying some comments as “Yes”, “No” or “?” required some interpretation Should HHS pursue regulatory change to hold IRBs/IORGs directly accountable for compliance with certain requirements of 45 CFR part 46? YESNO? 2163 Note: Classifying some comments as “Yes”, “No” or “?” required interpretation.

12. Key Question Asked Should HHS pursue regulatory change to hold IRBs/IORGs directly accountable for compliance with certain requirements of 45 CFR part 46? IRBs, Investigators Non- Governmental Organizations Private Sector Individuals YES7113 NO204 ?003

13. Questions Asked ANPRM included 7 specific questions, including the key question discussed previously

14. Review of Comments – Question 1 Is there sufficient need for HHS to pursue a regulatory change to 45 CFR part 46 to hold IRBs/IORGs directly accountable?

15. Review of Comments – Question 1 Yes (21)  Typical comment: proposed change is desirable and will have intended effect. Notable comments:  Proposal promotes consistency with FDA regulations  Regulation not needed—a change in guidance would allow OHRP to hold IRBs/IORGs directly accountable.  Proposal may not increase reliance on external IRBs, but nevertheless should be pursued. No (6)  Typical comments: proposed change is not desirable and will not have intended effect; may result in more confusion and administrative burden; guidance is preferable.

16. Review of Comments – Question 2 Would the proposed regulatory change reduce concerns about regulatory liability and contribute to an increase in collaborative IRB review arrangements?

17. Review of Comments – Question 2 Yes (14)  Typical comments: Proposed change will reduce concerns about regulatory liability and encourage collaborative IRB review arrangements. No (3)  Typical comments: While proposed change may reduce concerns about regulatory liability, it will not affect an institution’s decision about whether to rely on an external IRB. Regulatory liability is not the main factor. Yes & No (4)  Typical comments: Will decrease concern about regulatory liability for institutions considering reliance on an external IRB, but increase liability concerns for external IRBs/IORGs.

18. Review of Comments – Question 2 Notable comments:  Liability of individual IRB members is a concern.  Liability with respect to private parties persists  Local context considerations remain  Quality of IRB review remains a concern, which could be mitigated by accreditation

19. Review of Comments – Question 3 Are there other approaches and strategies that would decrease concern about regulatory liability and increase collaborative IRB review arrangements?

20. Review of Comments – Question 3 Yes (9) Notable comments:  OHRP should eliminate requirement that IRBs be designated on FWA and permit commitment to use only registered IRBs (relates to SACHRP recommendation)  Mitigate concern about quality of IRB review through voluntary/mandatory accreditation  Consider ways to reduce liability of individual IRB members  HHS funding agencies should strongly encourage collaborative IRB review  OHRP should issue guidance and template IRB Authorization Agreements No (1)

21. Review of Comments – Question 4 Would such a regulatory change have the unintended effect of making IRB organizations less willing to have their IRB designated on other institutions’ FWAs or have other unintended effects? If so, would there still be sufficient benefit to pursue the proposed regulatory change? Other possible negative consequences?

22. Review of Comments – Question 4 Yes (8)  Typical comment: The proposal will make IORGs less willing to serve as external IRBs, but support proposal despite this Notable comments:  Academic medical centers will become less willing to have their IRBs serve as external IRBs, while “commercial” IRBs would not  IRB members may become less willing to serve if to be held individually accountable No (4) Notable comments:  No change for IRBs that review FDA-regulated research

23. Review of Comments – Question 5 If such a regulatory change were pursued, what kinds of administrative actions would be appropriate for OHRP to take against IRBs found to be out of compliance?

24. Review of Comments – Question 5 Comments (13) Notable comments:  OHRP enforcement should be the same as FDA’s  Current OHRP sanctions are insufficient. OHRP should consider use of fines and seek such authority if it does not currently exist  The same administrative actions against institutions engaged in research should apply to IRBs/IORGs

25. Review of Comments – Question 6 How should regulatory requirements be categorized? Regulatory requirements seem to fall into three categories of responsibilities: 1. Responsibilities unique to IRBs/IORGs 2. Responsibilities unique to institution engaged in human subjects research 3. Responsibilities that may be fulfilled by either IRBs/IORGs or institutions engaged in human subjects research.

26. Questions Asked 6a-d. Are these categories appropriate? Is there a category of responsibilities that are inherently shared by the IRBs/IORGs and engaged institutions? Are the regulatory provisions identified under each category appropriate? How have institutions engaged in research and external IRBs/IORGs divided or shared regulatory responsibilities in the past?

27. Review of Comments – Question 6 Yes (11)  Typical comment: Proposed regulatory categories are appropriate and the regulatory provisions identified under each of the categories are appropriate. Notable comments:  While no disagreement about the categories, recommends a simplification to a single category that identifies the minimum regulatory responsibilities of the reviewing IORG. No (3)  Typical comments: There is a category of responsibilities that are shared by IRBs/IORGs and engaged institutions; there are some regulatory provisions that should be moved to another regulatory category.

28. Review of Comments – Question 7 7a. If this regulatory change is pursued, should OHRP use the IRB Authorization Agreement or other forms of agreement to inform its compliance oversight evaluations?

29. Review of Comments – Question 7a Yes (8) Notable comments:  Form of agreement used is not important  OHRP should develop detailed template IRB Authorization Agreement No (1)

30. Review of Comments – Question 7 7b. Should there be new provisions that require specific content for agreements between external IRBs and FWA-holding institutions?

31. Review of Comments – Question 7b Yes (6)  Comments: Some commenters wanted the regulation to include content for agreements in only the broadest terms, others seemed to prefer more specificity. No (5)  Typical comment: Flexibility is desirable.

32. Review of Comments – Question 7 7c. Should the regulation describe which regulatory requirements would need to be met by external IRBs versus institutions engaged in research?

33. Review of Comments – Question 7c Yes (7)  Typical comment: The regulation should describe which entity would be held accountable for each regulatory provision. No (6)  Typical comment: Flexibility is desirable, guidance is preferable.

34. Additional Information Reports from 2005 and 2006 meetings on alternative IRB models: http://www.dhhs.gov/ohrp/sachrp/documents/Alt ModIRB.pdf http://www.dhhs.gov/ohrp/sachrp/documents/Alt ModIRB.pdf http://www.aamc.org/research/irbreview/irbconf0 6rpt.pdf http://www.aamc.org/research/irbreview/irbconf0 6rpt.pdf Advanced Notice of Proposed Rulemaking published March 5, 2009 (see http://edocket.access.gpo.gov/2009/pdf/E9- 4628.pdf) http://edocket.access.gpo.gov/2009/pdf/E9- 4628.pdf