1. IRBSHARE: STREAMLINING IRB REVIEW FOR MULTI- SITE STUDIES

2. BACKGROUND The need to streamline IRB review

3. IRBshare Development Considerations Flexibility in federal regulations (OHRP 45 CFR 46.114 and FDA 21 CRF 56.114) Institutions can use a “joint review” arrangement and “rely upon the review of another qualified IRB…avoiding duplication of effort” Lessons learned from centralized models Disease-specific models are inherently restrictive Numerous contractual agreements (i.e., study-specific MOUs) can be burdensome CIRBs can have intensive startup costs and/or ongoing overhead CIRBs provide little flexibility for local IRBs Ongoing debate regarding external IRB’s ability to fully understand local context issues

4. Conference Series Grant Support Vanderbilt awarded R13: “Novel IRB Review Models for Efficient Multisite Review” Three meetings from 2011-2013 Goal was to develop, build, and pilot new model(s) of IRB review of multisite studies Multiple stakeholders Individuals from nearly 2/3s of the CTSAs, OHRP, FDA, NCATS Regulatory, legal, ethics, and clinical trial experts Iterative development Ongoing evaluation Start small: establish reliance for initial study review first, then expand

5. THE IRBshare MODEL How IRBs use IRBshare

6. IRBshare: General Features Universal terms of use preclude lengthy negotiations All institutions sign a one-time master agreement without site- specific modifications or study-specific language Inclusive consortia broadens model utilization IRBshare network is open to any FWA-holding organization and any area of research Low cost strengthens sustainability IRBshare network is free to join and has little to no overhead or startup costs

7. IRBshare: Shared Review Model Local investigator submits study to local IRB; study reviewed by convened IRB upload Local investigator submits study to local IRB; study reviewed by local subcommittee (>1 IRB member) using IRBshare documents FULL BOARD REVIEW SITE SHARED REVIEW SITE Committee Responsibility: Determine whether study meets all federal regulatory guidelines for approval of research (e.g., 45 CFR 46.111) Subcommittee Responsibility: Verify full board review site’s determination + review for site’s own local context issues IRB application Consent form(s) Protocol + IB/Device Manual Meeting minutes (redacted) Determination letter download

8. Discuss, review, and approve changes to the protocol, Investigator Brochure and/or Device Manual based on reported events/problems CC disseminates study- related materials and updates Local investigator submits to local IRB, who can then download IRB approval documents from IRBshare and review and approve the study via a local subcommittee. No documents are uploaded to IRBshare by the Shared Review Sites. The direction of the arrows is indicative of the information flow. Local IRB--now a Full Board Review Site--uploads IRB approval documents to IRBshare Study Coordinating Center (CC) (e.g., CRO, lead site) DSMB Local Investigator, Institution A Local Investigator, Institution B Local Investigator, Institution C Local IRB IRBshare Web-based System Local investigator reports adverse events/unanticipated problems to local IRB, and then the CC (if necessary) IRBshare Information Flow for Multicenter Study

9. IRBshare: Reliance Model Features Reliance model enables simultaneous IRB approval Once IRB approval uploaded to IRBshare, all study sites can seek approval Flexible reliance options support local autonomy “Lead” IRB established organically on study-by-study basis Studies may have more than one “lead” IRB IRBs always have the option to review study locally Local submission processes and forms do not have to change Dynamic IRB responsibilities address local IRB oversight concerns Local context review is always the responsibility of the local IRB Local IRB regains study oversight after relying on Full Board Review Site All study-related events are reported locally, with study-wide issues also reported broadly via the mechanism established for the study Shared IRB documents minimize submission requirements at local IRBs Once IRB approval documents uploaded to IRBshare, local IRBs can accept shortened IRB applications (e.g., local context only) from local investigators

10. IRBshare: Additional Features Transparency enables continuing education and dialogue Sharing IRB documentation enables continuing education and dialogue between IRBs Shared documents creates opportunity to utilize shared expertise, consult other IRBs, and promote consistency in the IRB review process

11. IRBshare TO DATE October 2012 to present

12. Who Can Use IRBshare? Any institution with a Federalwide Assurance with OHRP (i.e., most institutions) Any industry-sponsored or investigator-initiated multi-site study Any number of institutions (>1 up to ∞) Greater than minimal risk studies (i.e., full board review required)

13. IRBshare Network (n=36) *AAHRPP accredited; †CTSA institution or affiliate Baystate Health*University of Alabama Birmingham*† Boston University Medical Center*†University of Arkansas for Medical Sciences*† Children’s National Medical Center*†University of California San Diego† Duke University*†University of Illinois Chicago*† Maine Medical Center*University of Iowa*† Marshall University*University of Kansas*† Medical University of South Carolina*†University of Kentucky*† Meharry Medical College†University of Miami† Mississippi State University*University of Minnesota*† Mount Sinai Medical School*†University of North Carolina at Chapel Hill *† New York University School of Medicine*†University of Pittsburgh*† North Shore LIH Health SystemUniversity of Southern California*† Seattle Children’s HospitalUniversity of Texas HSC at San Antonio*† Stanford University*†University of Texas Southwestern Medical Center† The Scripps Research Institute†University of Washington† The University of Utah*†Vanderbilt University*† Tufts Medical Center†Virginia Commonwealth University*† Tufts University †Washington University (St. Louis) *†

14. Preliminary Results Regulatory Acknowledgement (OHRP, FDA, AAHRPP) 4 active studies with shared reviews conducted ISCHEMIA Trial: Duke relied on Vanderbilt Days from Submission to Approval: 6 MENDS II: Baystate relied on Vanderbilt Days from Submission to Approval: 42 Vitamin D & Type 2 Diabetes: MUSC relied on Tufts Days from Submission to Approval: 27 Neonatal Abstinence Syndrome Study: Vanderbilt relied on Tufts Days from Submission to Approval: 16 Recommended use mentioned in federal RFAs Recent U54 Rare Disease RFA stated that “applicants are strongly encouraged to consider models that will facilitate “shared review” such as IRBshare or a central IRB of record for multisite trials and provide plans for implementation.”

15. IRBshare FOR STUDY TEAMS AND INVESTIGATORS

16. Applying for a multicenter grant? 1. Utilize the grant template language IRBshare.org/#resources IRBshare.org/#resources 2. List the # of study sites in IRBshare 3. Recruit non-IRBshare sites a) Ask site PIs to email their IRB Director re: IRBshare and CC: emily.sheffer@IRBshare.orgemily.sheffer@IRBshare.org b) Email emily.sheffer@irbshare.orgemily.sheffer@irbshare.org i. Study title ii. Study sites iii. Site PI names and emails iv. IRB Director names and emails c) IRBshare can help reach out to site IRB Director(s)

17. Want to encourage an institution to join IRBshare? Encourage your colleagues at other institutions to talk to their IRB Director about IRBshare Sites join by having their Institutional Official sign the IRBshare Master Agreement (IMA)IRBshare Master Agreement (IMA) CC emily.sheffer@IRBshare.orgemily.sheffer@IRBshare.org

18. Not sure if a study is in IRBshare? Visit https://IRBshare.org/#studieshttps://IRBshare.org/#studies Contact your IRBshare Liaison (https://IRBshare.org/#participants) or email emily.sheffer@irbshare.orghttps://IRBshare.org/#participants emily.sheffer@irbshare.org

19. Lead site for a multi-site study? Notify your IRBshare Liaison ASAP (https://IRBshare.org/#participants)https://IRBshare.org/#participants Submit a cover letter with your IRB submission Tell collaborating PIs to contact their IRBshare liaison ASAP

20. Participating in study that has IRB approval in IRBshare? Contact your IRBshare liaison ASAP Submit your IRB application as usual to your IRB Include a cover letter indicating that an approval is in IRBshare

21. IRBshare Checklist for Study Teams https://www.ctsacentral.org/editor/index.php?doc_id=3843

22. IRBshare FOR INDUSTRY SPONSORED STUDIES Ensure Proper Access to Study Documents

23. Overview IRBshare can be used with industry sponsored study with the approval of the sponsor IRBshare will obtain study sites from the sponsor and enable only IRBs at those sites to view study documents. Sites can be added/removed as needed

24. Creating Industry-Sponsored Studies

25. If sponsor isn’t listed in IRBshare… IRBshare users can request that new sponsors be added IRBshare administrator will contact sponsor to verify study should be added to IRBshare + confirm study sites

26. Access to Industry-sponsored Studies is Limited IRBshare administrator can quickly and easily indicate which IRBshare institutions are study sites remove sites that drop from the study, as directed by Sponsor