1. VA Central IRB Annette R. Anderson, MS, RHIA, CIP VA Central IRB Administrator HRPP 101, September 2010

2. 2 Why the Need for a VA Central IRB? New opportunities Electronic age Larger, more complex studies Faster translation to clinical care New risks Database Research (e.g., Medicare) Genomics Research 2

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

4. 4 Projects Reviewed by VA Central IRB VA-funded studies only with some exceptions (SPRINT study) VA facilities that do not use the VA Central IRB will not be able to participate in projects reviewed by the VA Central IRB; in other words, there can be no IRB shopping 4

5. 5 5 Local VA Facility Requirements Local VA facilities that plan to use the VA Central IRB must: 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 standard operating procedures (SOPs) for using the VA Central IRB as an IRB of record Modify affiliate MOU if appropriate

6. 6 6 Local 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)

7. 7 Memorandum of Understanding Spells out the respective authorities, roles and responsibilities of the VHA Central Office Human Research Protection Program (HRPP), the VA Central IRB, and the local VA facility Requires the IO to appoint the local site representatives to do the following: Provide comments to VA Central IRB on initial project review determinations Provide final local site participation decision Serve as local site liaison with VA Central IRB

8. 8 VA Central IRB Operations No charge to the field for using the VA Central IRB Staffed by PRIDE Monthly meetings or more frequently as needed Ad hoc expert advisors VA Central IRB website 8

9. 9 VA Central IRB Reviews Convened Board Expedited Exempt Continuing Waiver of HIPAA-compliant authorization Does not review emergency use of a test article 9

10. 10 VA Central IRB Composition 19 voting members from across the country, including two Co-Chairs 5 nonvoting members Ethics Legal Affairs Regulatory Affairs Privacy & HIPAA Information Security Officer 10

11. 11 Progress to Date 89 VA facilities have amended their FWA listing the VA Central IRB as an IRB of Record 35 studies reviewed involving over 280 sites since inception 78 SAE/UAP and 23 Protocol Deviation reports reviewed so far this calendar year Over 100 amendments processed (LSI and PI/SC) this calendar year 13 continuing reviews performed in 2010 to date 11

12. 12 Application Process 2 kinds of applications Principal Investigator (PI) or Study Chair (SC) Application Co-PI Supplement if applicable Coordinating Center Supplement if applicable Local Site Investigator (LSI) Application

13. 13 PI/SC Application Process PI or SC enlists local VA facilities Check VA Central IRB web site to see if all potential participating sites have listed the VA Central IRB as an IRB of record 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 that are not listed ASAP

14. 14 Key Elements of the PI/SC Application Protocol must clearly differentiate clinical from research activities Protocol must be consistent with The PI/SC Application Informed consent form HIPAA authorization

15. 15 Key Elements of the PI/SC Application Protocol must contain sufficient information for the IRB to evaluate all regulatory criteria for approval of research Model informed consent documents and recruitment materials Waiver requests and vulnerable population supplements Signed by PI/SC, PI/SC’s supervisor, and ACOS/R&D of PI/SC local site

16. 16 Administrative and Designated Reviews Administrative Review by assigned VA Central IRB Coordinator and Regulatory Advisor Primary Reviewer System with extensive use of reviewer checklists Privacy Officer and Information Security Officer Reviews Any reviewer can contact investigator for response to questions or they can go through VA Central IRB staff Ad hoc reviewers as needed

17. 17 Potential VA Central IRB Actions Approve the study Approve the study contingent upon minor modifications (Convened Board) Approve contingent upon local site comment Require Modifications (Expedited Review) Defer the study pending major modifications Disapprove

18. 18 Local Site Initial Review After the PI/SC application is approved contingent upon local site comment, or approved contingent upon minor modifications A copy of the approved PI/SC Application packet is sent to each local site for review, along with a copy of the VA Central IRB approval letter Local Site Investigators (LSIs) can begin preparing LSI applications

19. 19 Local Site Initial Review Each local site has 30 days to provide comments to the VA Central IRB New form has been developed for this purpose Comments must be provided to the VA Central IRB by the individual designated by the medical center director; this is usually one of the following: R&D Chair; Local IRB Chair; ACOS or AO for R&D

20. 20 LSI Application Process Each Local Site Investigator (LSI) prepares a Local Site 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

21. 21 Review of Local Site Comments VA Central IRB reviews all local site comments and decides if changes are needed as follows: No changes needed; comments or questions only were received, or a no further comments response provided Changes in PI/SC Application (may or may not affect LSI Applications;) Local changes in LSI Application only (affects only local site making comment)

22. 22 Review of Local Site Investigator Applications Usually reviewed in conjunction with local site comments but can be reviewed after depending upon timing of receipt Review by convened IRB or by expedited review procedures with review outcomes: Approved Approved Contingent on minor modifications Deferred for Major Modifications Disapproved

23. 23 Local Facility Participation Decision Once a LSI Application is approved, local VA facilities have 10 work days to decide whether or not to participate If a facility decides to participate, a copy of the applicable VA Central IRB minutes is posted to its SharePoint site A facility can still suggest changes but if the VA Central IRB, PI, or LSI do not accept the changes and the facility decides not to participate, the site cannot participate in the study

24. 24 Local Facility Approval 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 Copy of Local VA facility approval must be forwarded to VA Central IRB, as well as to LSI Sites added after a study is approved are not given 30-day comment period; however, a site can always make a comment

25. 25 Continuing Review VA Central IRB staff notifies PI and LSIs of continuing review deadlines Each local participating site submits a continuing review report to PI/SC PI/SC prepares summary report and submits to VA Central IRB, along with copies of LSI reports Continuing review date is set for the study, not for each specific site so that all sites for a given study get on the same review cycle

26. 26 Adverse Events, Unanticipated Problems, Protocol Deviations, and Complaints These must be reported to VA Central IRB, not the local IRB Table of Reporting Requirements is on the VA Central IRB website and is forwarded with each final approval letter Specific Reporting forms for Adverse Events, Unanticipated Problems, and Protocol Deviations on website Other reports of noncompliance or complaints must be reported as they are received

27. 27 Future Plans – Coming Soon Improve communications with sites by improving website content; instituting periodic webinars for new site liaisons and for when changes occur Step 2 AAHRPP Application submitted; awaiting dates for site visit Solicit feedback from investigators and sites for 2010 annual review of VHA HRPP Revise Memorandum of Understanding to incorporate changes and improve communication Effective October 1, 2010, all new ORD-funded multisite studies must be submitted to VA Central IRB

28. 28 Future Plans – Coming Later Ongoing formal peer-reviewed evaluation Create a second VA Central IRB as workload increases – end of calendar year 2011 Develop electronic system for submissions and document management, in addition to SharePoint

29. 29 Contact Information Annette Anderson, MS, RHIA, CIP VA Central IRB Administrator 202-461-1813; annette.anderson3@va.govannette.anderson3@va.gov Website http://www.research.va.gov/programs/pride/cirb/default.cfmhttp://www.research.va.gov/programs/pride/cirb/default.cfm Toll free number 1-877-254-3130 Email va.central.irb@va.govva.central.irb@va.gov