Julie Kaneshiro and Ivor Pritchard HHS Office for Human Research Protections

1. CTSA –NICHD Workshop on Comparing IRB Models for Multi-site Pediatric Research Studies:OHRP PerspectiveApril 23, 2009 Julie Kaneshiro and Ivor Pritchard HHS Office for Human Research Protections

2. Topics • Current regulatory flexibility • Cooperative review arrangements • Designation of IRBs • OHRP co-sponsored meetings on alternative IRB models • Proposal to hold IRBs directly accountable • Issues to consider

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

4. 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

5. Current Regulatory Flexibility • Additional points: • IRBs must be registered to be designated on an FWA • When designating an external IRB an IRB Authorization Agreement must be developed

6. Meetings on Alternative IRB Models • Secretary’s Advisory Committee on Human Research Protections recommendation: 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 (Fall, 2004).

7. 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

8. Meetings on Alternative IRB Models • A key conclusion: Despite existing regulatory flexibilities some institutions remain reluctant to designate external IRBs and rely on cooperative review arrangements.

9. 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.

10. OHRP Proposal to Hold IRBs Accountable • Should OHRP revise 45 CFR part 46 to enable HHS to hold IRBs and IRB organizations (IORGs) directly accountable for compliance? • An Advanced Notice of Proposed Rulemaking published March 5, 2009 (see http://edocket.access.gpo.gov/2009/pdf/E9-4628.pdf) • Comments due by June 3, 2009

11. Proposal to Hold IRBs Accountable Issues to consider: • FDA’s IRB regulations explicitly include compliance provisions (21 CFR part 56) • Is there sufficient need for HHS to pursue a regulatory change to 45 CFR part 46 to hold IRBs directly accountable?

12. Proposal to Hold IRBs Accountable • Would such a regulatory change have the unintended effect of making IORGs less willing to have their IRB designated on other institutions’ FWAs? • How should the IRB authorization agreement be used to inform OHRP’s compliance oversight evaluations?

13. Proposal to Hold IRBs Accountable • How should OHRP categorize the responsibilities of the IRB/IORG and FWA holding institution? Regulatory requirements seem to fall into three categories of responsibilities.

14. Proposal to Hold IRBs Accountable • Categories of regulatory responsibilities: • Responsibilities unique to IRBs/IORGs; • Responsibilities unique to institution engaged in human subjects research; • Responsibilities that may be fulfilled by either IRBs/IORGs or institutions engaged in human subjects research. • Is there a category of responsibilities that are inherently shared by the IRBs/IORGs and engaged institutions?

15. Proposal to Hold IRBs Accountable • Responsibilities that may be unique to IRBs/IORGs; a few examples: • Provisions regarding IRB membership (45 CFR 46.107) • Provision that identifies criteria for IRB approval of research (45 CFR 46.111) • Provision that permits IRB to alter or waive informed consent (45 CFR 46.116(c) and (d))

16. Proposal to Hold IRBs Accountable • Responsibilities that may be unique to engaged institutions; a few examples: • Requirement that investigator obtain IRB review and approval before beginning non-exempt human subjects research (45 CFR 46.109(a)) • Requirement that no investigator conduct non-exempt human subjects research without obtaining and documenting subjects’ informed consent unless an IRB has waived these requirements (45 CFR 46.116 and 46.117).

17. Proposal to Hold IRBs Accountable • Responsibilities that may be fulfilled by IRB/IORG or engaged institutions; a few examples: • Determining applicability of 45 CFR part 46 (e.g. exemptions) (45 CFR 46.101(b)) • Developing written IRB procedures which IRB will follow (45 CFR 46.103(b)(4)) • Fulfilling documentation and recordkeeping requirements associated with IRB activities (45 CFR 46.115)

18. Resources • OHRP Assurances webpage: http://www.hhs.gov/ohrp/assurances/assurances_index.html • OHRP FWA FAQS: http://www.hhs.gov/ohrp/FWAfaq.html • OHRP IRB registration FAQS: http://www.hhs.gov/ohrp/IRBfaq.html • Reports from 2005 and 2006 meetings on alternative IRB models: • http://www.dhhs.gov/ohrp/sachrp/documents/AltModIRB.pdf • http://www.aamc.org/research/irbreview/irbconf06rpt.pdf