VA Central IRB From Concept to Reality

1. VA Central IRBFrom Concept to Reality K. Lynn Cates, MD Assistant Chief Research & Development Officer Director, PRIDE October 7, 2009

2. Human Research Has Changed • More multi-site than single site studies • New opportunities • Electronic age • Larger, more complex studies • Faster translation to clinical care • New risks • Information security with large databases (e.g., Medicare & genomics research)

3. VA Central IRBPurpose • Improve human research protection in ORD multi-site studies by ensuring • Consistent expert ethical & scientific review • Local issues are addressed • Enhance efficiency of IRB reviews

4. VA Central IRBAdvantages • Consistent expert ethical & scientific review • More training & experience for IRB in reviewing complex multi-site studies • Centralized investigator accountability • Earlier identification of trends in adverse events • Model for local VA IRBs • More efficient IRB review of multi-site studies • Potential to facilitate translation of research to clinical care

5. VA Central IRBLogistics • No charge to the field for using the VA Central IRB • Monthly meetings • Ad hoc expert advisors • VA Central IRB website • Staffed by PRIDE in ORD

6. VHA Central Office HRPPReporting Relationships Institutional Official = Principal Deputy Under Secretary for Health Human Protections Administrator = Chief R&D Officer Director PRIDE VA Central IRB Administrative Staff

7. VA Central IRBLogistics • ORD studies only • All CSP studies will go to the VA Central IRB • Other ORD Services (e.g., RR&D, HSR&D, QUERI), not investigators, will refer studies to the VA Central IRB • VA facilities that do not use the VA Central IRB will not be able to participate in projects reviewed by the VA Central IRB

8. VA Central IRB Composition • 20 voting members • 5 nonvoting members • Ethics • Legal Affairs • Regulatory Affairs • Privacy & HIPAA • Information Security Officer

9. VA Central IRB Reviews • Full • Expedited • Exempt • Continuing • Waiver of HIPAA-compliant authorization

10. VA Central IRBLocal Accountability • Concept of Human Research Protection Program (HRPP) vs. IRB • Every VA facility that performs human research has ultimate responsibility for its HRPP, even if it uses an external IRB (e.g., affiliate’s, another VA’s or the VA Central IRB)

11. Local VA Facilities That Plan to Use the VA Central IRB as an IRB of Record • Amend their FWAs to include the VA Central IRB as one of their IRBs of record • Enter into a Memorandum of Understanding (MOU) with VHA Central Office • Develop SOPs for using the VA Central IRB • [When applicable, revise MOU with affiliate]

12. VA Central IRBApplication Process • 2 kinds of applications • Principal Investigator (PI) or Study Chair (SC) Application • Local Site Investigator (LSI) Application

13. VA Central IRBPI/SC Application Process • PI or SC enlists local VA facilities • Check VA Central IRB web site to see if all potential participating sites have completed the process of listing the VA Central IRB as an IRB of record (http://www.research.va.gov/programs/pride/cirb/facilities.pdf) • If not listed, verify with the VA facility that it can perform human research (i.e., that it has a Federalwide Assurance (FWA)) • Notify VA Central IRB staff of all potential participating VA facilities ASAP

14. VA Central IRBKey Elements of Application • Protocol must clearly differentiate clinical from research activities • Protocol must be consistent with • Local Site Investigator (LSI) Application • Informed consent form • HIPAA authorization

15. VA Central IRBKey Elements of Applications • Protocol must contain sufficient information for the IRB to evaluate all regulatory criteria for approval of research • FDA issues must be addressed (e.g., IND or IDE status) • Potential future use of data or specimens must be clearly described in protocol, informed consent, & HIPAA authorization

16. VA Central IRB Potential Actions on PI/SC Application • Approve the study • Approve the study contingent upon minor modifications • Table the study pending major modifications

17. VA Central IRBApplication Process • After the PI/SC application is approved by the VA Central IRB, or approved contingent upon minor modifications • A copy of the approved PI/SC Application packet is sent to each local site • Each local site has 30 days to provide comments to the VA Central IRB

18. VA Central IRBLSI Application Process • Each Local Site Investigator (LSI) prepares a LSI Application based on PI/SC Application • The PI/SC reviews all LSI Applications for consistency • The VA Central IRB will require a justification for any differences among the LSI Applications including the informed consent forms

19. VA Central IRBProcess • VA Central IRB reviews all LSI applications & comments from local sites • VA Central IRB is final arbiter of • Changes to the PI/SC & LSI Applications • Global changes in protocol (affect all sites) • Local changes in protocol (affect local site)

20. VA Central IRBProcess • Local VA facilities have 10 days to decide whether or not to participate • Local VA facility must approve the research in accordance with VHA Handbook 1200.01 (R&D Committee) and local procedures before research can be initiated at that facility • Other sites may be added later (but only have a 10 day comment period, and can only make local modifications)

21. VA Central IRB First Year of Operation • August 2008 - reviewed first study • September 2009 • 70 VA facilities have signed up • 19 studies received for review involving @ 150 VA facilities • 9 studies approved • Streamlining process to make it more efficient & user friendly

22. VA Central IRBPlans for Second Year and Beyond • March 2010 - apply for AAHRPP accreditation • Ongoing formal peer-reviewed evaluation • Split the IRB into 2 or more IRBs

23. VA Central IRBContact Information Lynn Cates, MD (202) 461-1811 lynn.cates@va.gov Annette Anderson VA Central IRB Administrator (202) 461-1813 annette.anderson3@va.gov