1. Status of SACHRP Recommendations July 2003-October 2008 Meeting of the Secretary’s Advisory Committee on Human Research Protections October 27, 2008 Michael A. Carome, M.D. CAPT, U.S. Public Health Service Associate Director for Regulatory Affairs Office for Human Research Protections

2. Overview Process for HHS review of SACHRP recommendations Possible outcomes following HHS consideration of SACHRP recommendations Status of SACHRP recommendations Questions and discussion

3. Process for HHS review of SACHRP recommendations SACHRP approves recommendation OHRP prepares letter for SACHRP Chair signature Transmittal memo through the Assistant Secretary for Health to the Secretary Secretary acknowledgement and referral to appropriate agency or office for consideration

4. HHS Consideration of SACHRP Recommendations – Possible Outcomes (1) Adopt the recommendation as made Adopt the recommendation with modifications Defer taking any action regarding the recommendation

5. HHS Consideration of SACHRP Recommendations – Possible Outcomes (2) OHRP or other HHS agencies revise existing guidance or develop new guidance Modify existing regulations or implement new regulations HHS convenes conference or workshop Other

6. Status of SACHRP Recommendations

7. Categories of Recommendations (1) Research involving children and subpart D of 45 CFR part 46 (38) Accreditation of human research protection programs (HRPPs) (5) Adverse event reporting (1) Research involving pregnant women and subpart B of 45 CFR part 46 (1) HIPAA Privacy Rule (9) Research involving prisoners and subpart C of 45 CFR part 46 (9)

8. Categories of Recommendations (2) OHRP/NIH/FDA convene workshop on central IRB review mechanisms (1) Subpart A of 45 CFR part 46 (79) Tribal authority over research involving American Indian or Alaska Native populations (1) Research in disaster settings (2) Review of the human subjects protection system (1) Total number of recommendations: 147

9. Research Involving Children and Subpart D (1) 6 multi-part recommendations regarding § 46.407 (July 8, 2004). – Most of recommendations implemented via OHRP’s May 26, 2005 guidance on the 407 review process and OHRP’s and FDA’s implementation of a joint review process for research regulated by both agencies. – FDA issued guidance on its process under 21 CFR 50.54. – Algorithm for analysis under subpart D (part of recommendation I) still under consideration by OHRP. – Recommendation regarding a SACHRP subcommittee assessing aspects of 407 process implementation and making annual reports (part of recommendation VI) not implemented.

10. Research Involving Children and Subpart D (2) 7 recommendations regarding § 46.404 (research not involving greater than minimal risk). 5 recommendations regarding § 46.405 (research involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects). 4 recommendations regarding § 46.406 (research involving greater than minimal risk and no prospect of direct benefit, but likely to yield generalizable knowledge about the subject’s disorder or condition). (July 28, 2005) – Recommendations would require development of new guidance and are under consideration by OHRP, along with many other recommendations made by the IOM.

11. Research Involving Children and Subpart D (3) 3 recommendations regarding § 46.402 and child assent. 3 recommendations regarding parental permission and its waiver under § 46.408(c) for research designed for conditions for which parental or guardian permission is not a reasonable requirement to protect subjects. 6 recommendations regarding § 46.409 and research involving children who are wards. 4 recommendations involving the provisions of § 46.116(d) vis-á-vis waiver of parental permission. (November 9, 2006) – Recommendations would require development of new guidance and are under consideration by OHRP, along with many other recommendations made by the IOM.

12. Accreditation of HRPPs – July 8, 2004 (1) Recommendation I: Premature for OHRP, FDA, or other government agencies to offer incentives to research institution to seek accreditation. – No such incentives have been implemented by HHS. Recommendation II: There should be a future systematic evaluation of HRPP accreditation. – No specific action taken by HHS to date. Recommendation III: Government should have no role in endorsing one accreditation organization over another. – OHRP/FDA/HHS agree and have not issued any such endorsement.

13. Accreditation of HRPPs – July 8, 2004 (2) Recommendation IV: After an assessment of the impact of accreditation (assuming a positive outcome) appropriate government agencies should develop, if warranted, a list of incentives for research institutions that seek accreditation. – Premature to take action on this recommendation. Recommendation V: HHS should organize a conference involving all major stakeholders to examine a wide range of self regulatory initiatives over the past 4 years, of which certification of IRB professionals is furthest along. – No action taken by HHS to date.

14. Adverse Events Recommendation: OHRP and FDA should promptly issue clear and consistent joint guidance on IRB review of both internal and external adverse event reports which will best serve to protect human subjects and effectively reduce regulatory burden (July 8, 2004). – The Federal Adverse Events Taskforce was formed in 2004. – OHRP issued draft guidance on unanticipated problems and adverse events for public comment in October 2005 and final guidance in January 2007. – FDA convened a Part 15 Hearing in March 2005. FDA issued draft guidance on adverse events for public comment in April 2007. The final guidance is in agency clearance.

15. Research Involving Pregnant Women and Subpart B Recommendation: OHRP should develop guidance on subpart B regarding how to interpret “biomedical knowledge” in broadest possible sense, and the requirement that data cannot be collected by any means other than by enrolling pregnant women. The guidance should stress the appropriate use of the exemption clause. (July 27, 2004 SACHRP meeting) – Recommendation would require development of new guidance and is under consideration by OHRP.

16. HIPAA Privacy Rule 9 detailed recommendations, including recommendations that (1) disclosure of protected health information (PHI) for research purposes be exempted from the Privacy Rule’s accounting requirements; (2) standards for de-identification of data be revised; and (3) the categories of research for which HIPAA authorizations are not required be expanded to include research exempt under the Common Rule (September 27, 2004). – The recommendations have been forwarded to the Office for Civil Rights and remain under consideration by that office.

17. Research Involving Prisoners and Subpart C 1 recommendation calling for extensive revision of subpart C. 8 recommendations regarding interpretation of current provisions of subpart C. (July 28, 2005) – The recommendation that a prisoner representative should be one of the reviewers when research involving prisoners is reviewed by an IRB under an expedited review procedure has been incorporated into OHRP guidance (see FAQs). – All other recommendations would require development of new guidance or revision of subpart C regulations and are under consideration by OHRP, along with many other recommendations made by the IOM.

18. Conference on Central IRBs (1) Recommendation that NIH, FDA, and OHRP 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 (July 28, 2005). – Such a workshop was held in November 2005, and a subsequent follow-up national conference was held in November 2006; both explored alternative IRB review models and reports of both events have been provided to the Subpart A Subcommittee and posted on OHRP’s website. – OHRP is preparing a Federal Register notice requesting information and comment on whether OHRP should hold IRBs directly accountable.

19. Conference on Central IRBs (2) Recommendation that NIH, FDA, and OHRP 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 (July 28, 2005). – FDA issued guidance on the use of a centralized IRB review process for multicenter clinical trials in March 2006.

20. Subpart A of 45 CFR Part 46 (1) 14 recommendations regarding continuing review: 13 recommendations called for revision of OHRP’s guidance regarding continuing review (with one calling for a similar action by FDA) and 1 called for an Advance Notice of Proposed Rulemaking to seek comment regarding a proposal to allow continuing review to occur less frequently than once per year (but not less than every 2 years). (March 14, 2007) – Recommendations are under consideration by OHRP. – FDA has developed draft guidance on IRB continuing review, and it is in agency clearance.

21. Subpart A of 45 CFR Part 46 (2) 6 recommendations regarding expedited review: 3 calling for revised OHRP and FDA guidance on expedited review, 1 calling for revision of the regulations by changing “expedited review” to “designated review,” 1 calling for specific revisions to expedited category 7, and 1 calling for OHRP review of the expedited categories every 5 years. (March 14, 2007) – OHRP published a Federal Register notice proposing revision of category 7 as recommended by SACHRP, proposing a clarifying revision to category 5, and seeking comment on the entire list. Public comment period is closed and comments are under review. – Recommendations regarding revised guidance and regulatory change are under consideration by OHRP.

22. Subpart A of 45 CFR Part 46 (3) 4 recommendations calling for new regulations requiring initial and continuing training of IRB members, IRB staff, investigators, and institutional officials. (June 15, 2007) – OHRP published a Federal Register notice seeking information and comment regarding whether additional guidance or regulation is needed regarding training and education of individuals who conduct or oversee human subjects research. The public comment period closed on September 29, 2008. OHRP received 96 comments and is reviewing them.

23. Subpart A of 45 CFR Part 46 (4) 6 recommendations regarding the interpretation of the provisions under § 46.116(d) for waiver of the requirements for obtaining informed consent. 6 recommendations regarding the interpretation of the definition of minimal risk at § 46.102(i). (January 31, 2008) – The recommendations have been transmitted to the Secretary. Acknowledgement from the Secretary is pending. – The recommendations will require new OHRP guidance and are awaiting consideration.

24. Subpart A of 45 CFR Part 46 (5) 27 recommendations regarding the exemptions. 4 recommendations regarding alternate models of IRB review. 2 recommendations regarding submission of IRB membership rosters to OHRP (1 would require rulemaking) 5 recommendations regarding waiver under § 46.117(c) of the requirements for documenting informed consent 5 recommendations regarding roles of institutional officials in protecting human subjects. (September 18, 2008) – The recommendations have been transmitted to the Secretary. Acknowledgement from the Secretary is pending. – Many recommendations will require new or revised OHRP guidance and are awaiting consideration.

25. Tribal Authority Over Research Involving American Indian or Alaska Native Populations 1 recommendation that HHS promote the development of guidance and grants policy in consultation with OHRP, other staff and operating divisions, and other appropriate departments and agencies that address research involving American Indian or Alaska Native Populations. (September 18, 2008) – The recommendations have been transmitted to the Secretary. Acknowledgement from the Secretary is pending.

26. Research in Disaster Settings 1 recommendation that HHS proactively recognize the critical importance of conducting research in the aftermath of disasters and promote planning for the ethical conduct of such activities. 1 recommendation that HHS conduct an assessment of the current ethical review process and, if indicated, the feasibility of developing additional processes through its relevant components. (September 18, 2008) – The recommendations have been transmitted to the Secretary. Acknowledgement from the Secretary is pending.

27. Review of the Human Subjects Protection System 1 recommendation that HHS explore opportunities for demonstration projects related to system-level changes in the human subjects protection system. (September 18, 2008) – The recommendations have been transmitted to the Secretary. Acknowledgement from the Secretary is pending.

28. Questions and discussion