1. IRBshare: Streamlining IRB Review of Multisite Studies EMILY SHEFFER, MPA | VANDERBILT UNIVERSITY MEDICAL CENTER | EMILY.SHEFFER@IRBSHARE.ORG

2. Brief History of IRBshare Funded by National Center for Research Resources (NCRR) (2011-2014) *New* model envisioned because use of IRB reliance was rare due to ◦Significant lack of trust between IRBs ◦Institutional/IRB policies against transferring oversight (still true for some institutions) Initial Project Goals ◦Maintain high level of protection for human subjects in multicenter trials ◦Accelerate study start Up ◦Create a scalable IRB reliance model (minimal funding required; open to all institutions) ◦Create transparency between IRBs to promote shared expertise and practices >30 Institutions CTSA Leadership, IRB Directors, Lawyers, Clinical Trial Experts Sponsors Sponsors Eli Lily, NIH, VA Regulatory Expertise Regulatory Expertise OHRP, AAHRPP, WIRB

3. IRBshare NATIONAL IRB RELIANCE MODEL TO STREAMLINE IRB REVIEW—WITHOUT TRANSFERRING IRB OVERSIGHT— WITH NO ADDITIONAL RESOURCES

4. Shared Review Model 1.Local investigator submits study to local IRB 2.Study reviewed according to risk level (expedited or full committee review) upload 1.Local investigator submits study to local IRB (abbrev application recommended) 2.Study reviewed by local subcommittee (>1 IRB member) using IRBshare documents LEAD IRB LOCAL OVERSIGHT IRB Committee Responsibility: 1.Determine whether study meets all federal regulatory guidelines for approval of research (e.g., 45 CFR 46.111) Subcommittee Responsibility: 1.Verify (not re-review) Lead IRB’s determination, AND 2.Review for site’s own local context issues IRB application Consent form(s) (become model consent(s)) Protocol + IB/Device Manual Meeting minutes (redacted) Determination letter download LOCAL IRB MAINTAINS OVERSIGHT BUSINESS AS USUAL Initial Study Review Continuing Review Study-wide amendments

5. STEP 1: Lead IRB identified by PIs and/or sponsor or funder. Lead IRB may be 1st IRB with approval IRB of Overall Study PI AND should be a site at which all or most study activities occur STEP 6: Approved ICF sent to other sites (by same entity as used in 4a) STEP 3: PI at Lead IRB submits study to Local IRB AS USUAL STEP 4b: Lead IRB reviews study as usual STEP 5: Lead IRB approves study, notifies Lead PI as usual, and uploads approval to IRBshare System. Initiating Use of IRBshare STEP 7: Local PIs submit to their Local IRB, following their local submission guidelines for IRBshare (see 4a). Study PIs discuss alternative Lead IRB options with other IRBs, if any. STEP 2: Site PI contacts IRBshare Liaison* with request to be Lead IRB YES NO *IRBshare Liaisons are the primary IRB contact at each siteIRBshare Liaisons Alternative Lead IRB Identified STEP 8: Local IRBs use Shared Review Process to approve study and note reliance on Lead IRB’s approval in IRBshare System. Study Teams IRBs STEP 4a: Notify* other site PIs with instructions to: Ask local IRB about submission procedures (e.g., use of abbreviated application); Wait to submit to their IRB until Lead IRB PI shares approved Informed Consent Form (ICF) *Whoever is coordinating study (e.g., Coordinating center, CRO, PI at Lead IRB, etc.) STEP 9: Local IRBs send approval letter to local investigator (note: letter may note of IRBshare). Local IRB remains IRB of record for local PI. ALL SITE PIs report local modifications, AEs, unanticipated problems, etc. to local IRB. Follow protocol regarding adverse event reporting to other sites. Repeat Steps 3-9 for continuing review and study-wide amendments.

6. Differences between IRBshare and Central IRBs IRBshare is a National IRB Reliance Model ◦IRBshare is open to any institution with an FWA and constituted IRB vs. select institutions per CIRB ◦IRBshare has a single master agreement to join vs. study-specific MOUs for a CIRB ◦IRBshare’s Lead IRB rotates (selected based on the study sites) vs. one institution as the constant CIRB IRBshare has Different Regulatory Responsibilities ◦IRBshare Lead IRB reviews for local institution only vs. CIRB reviewing for all study sites ◦IRBshare’s Local Oversight IRB (relying IRB) reviews for own local context vs. CIRB reviewing each site’s local context IRBshare PIs always submit and report to their local IRB vs. submitting to the CIRB and possibly the local IRB, too

7. Lead IRB/ CIRB Local/ Relying IRB Division of Responsibilities Across Models IRB and/or HRPP responsibilities are shared by sites in all reliance models Subtle differences in each model can create confusion for IRBS and investigators

8. Preliminary Results and Lessons Learned IRBSHARE MASTER AGREEMENT FINALIZED: OCTOBER 2012 FIRST RELIANCE: FEBRUARY 2013

9. IRBshare Scope and Eligibility Institutions ◦Any institution with an FWA and federally constituted IRB ◦AAHRPP not required, but captured for relying sites’ decision making Studies ◦All studies requiring IRB review (not applicable to exempt studies) ◦All diseases and conditions ◦All funders: Federal, industry, and investigator-initiated IRB Reviews Included ◦All Phase of Review: Initial study review, continuing review, and reviews of amendments

10. IRBshare Successes National Reliance Model: ◦59 institutions in 28 states ◦59 institutions in 28 states have executed single master reliance agreement ◦No funding required to support use Median of 14 days Accelerating Study Start Up: Median of 14 days from submission to approval (n=28 reliances; 79% studies are greater than minimal risk) Transparency ◦Shared Expertise—Institutions unable to transfer oversight can streamline their review ◦Shared Practices—IRBs communicating and sharing documents/templates

11. IRBshare Network (n=59) *AAHRPP accredited (n=44); †CTSA institution (n=39) States (n=28): Alabama Arizona Arkansas California Florida Illinois Iowa Kansas Kentucky Louisiana Maine Massachusetts Michigan Mississippi Minnesota New Mexico New York North Carolina Ohio Oregon Pennsylvania South Carolina Tennessee Texas Utah Virginia West Virginia Washington (Washington DC) Baystate Health*Oregon Health & Science University†University of Illinois Chicago*† Boston University Medical Center*†Pennington Biomedical Research Center*University of Iowa*† Children’s National Medical Center*†St. Claire Regional Medical CenterUniversity of Kansas*† Cincinnati Children’s Hospital Medical Center*†Seattle Children’s HospitalUniversity of Kentucky*† Columbia University*†Stanford University*†University of Miami† Duke University*†Texas A&M UniversityUniversity of New Mexico Health Sciences Center*† Louisiana State University A & M*The Rockefeller University*†University of North Carolina at Chapel Hill *† Louisiana State University HSC New Orleans*The Scripps Research Institute†University of Pennsylvania*† Louisiana State University HSC Shreveport*The University of Arizona*University of Pittsburgh*† Maine Medical Center*The University of Texas HSC at Houston*†University of Southern California*† Marshall University*The University of Utah*†University of Texas HSC at San Antonio*† Medical University of South Carolina*†Tufts Medical Center†University of Texas Southwestern Medical Center† Mayo Clinic*†Tufts University †University of Washington† Meharry Medical College†Tulane University*Vanderbilt University*† Michigan State University*University of Alabama Birmingham*†Virginia Commonwealth University*† Mississippi State University*University of Arkansas for Medical Sciences*†Wake Forest University Health Sciences* Mount Sinai Medical School*†University of California, Los Angeles†*Washington University (St. Louis) *† New York University School of Medicine*†University of California, San Diego†West Virginia University* North Shore LIH Health SystemUniversity of California, San Francisco*†Xavier University (Louisiana) Northwestern University †University of Cincinnati*†

12. Challenges (to all reliance models) IRB and PI understanding of responsibilities Coordination of use/Implementation across diverse studies and institutions Competing IRB priorities Managing expectations of IRBs and PIs (IRB reliance ≠ relinquishing HRPP or PI responsibilities) Including institutions without an FWA Small community hospitals

13. IRBchoice NHLBI-funded R01 to expand IRBshare’s master agreement and system to support multiple reliance models (full/ceded + shared) Goal: enable IRBs to identify the reliance model that works best for their PI and institution on a study-by-study basis Timeline: Release in Fall 2015 LEAD IRB ROLE FOR STUDY IRB of Record (only)Sharing IRB (only) IRB of Record --and-- Sharing IRB Relying IRB Options 1.Ceded review 2.Local review 1.Shared review 2.Local review 1.Ceded review 2.Shared review 3.Local review