1. IRBshare: Streamlining IRB Review of Multisite Studies

2. IRBshare Background >30 Institutions CTSA Leadership, IRB Directors, Lawyers, Clinical Trial Experts Sponsors Sponsors Eli Lily, NIH, VA Regulatory Expertise Regulatory Expertise OHRP, AAHRPP, WIRB 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

3. 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

4. IRBshare is NOT a Central IRB  Reduce duplicative IRB reviews and thus study start up  National reliance model supported by single master agreement for use with any study regardless of disease type, funder or type of human subjects review required  Ancillary reviews remain under local purview (biosafety, radiation safety, research billing/Medicare qualifying review)  Opportunity to streamline submission processes for investigators COMMONALITIES WITH OTHER RELIANCE MODELS

5. IRBshare is NOT a Central IRB  Minimal burden on Lead IRB  Minimal process changes for local IRBs  No additional funds required for IRBs  No investigator confusion regarding submissions or reporting: investigators always go to local IRB  Never requires multiple submissions by a site investigator (e.g., to cIRB and local IRB)  Avoids complex IRB negotiations around compliance, COI management, and reporting)  Provides transparency to promote consistent determinations, sharing of best practices, and communication between IRBs DIFFERENCES FROM OTHER RELIANCE MODELS

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

7. IRBshare Scope and Eligibility  Institutions  Any institution with an FWA and federally constituted IRB  AAHRPP accreditation is not required, but captured for relying sites’ decision making  Studies  All diseases and conditions  All studies that require IRB review  All funders: Federal, industry, and investigator-initiated  IRB Reviews Included  All Phases of Review: Initial study review, continuing review, and reviews of amendments

8. IRBshare Successes National Reliance Model: ◦64 institutions in 30 states ◦64 institutions in 30 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=38 reliances; 65% 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

9. IRBshare Network (n=64) *AAHRPP accredited (n=49); †CTSA institution (n=43) States (n=30): Alabama Arizona Arkansas California Florida Illinois Indiana Iowa Kansas Kentucky Louisiana Maine Massachusetts Michigan Minnesota Mississippi Missouri 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 Cincinnati*† Boston University Medical Center*†Ochsner Health System*University of Illinois Chicago*† Children’s National Medical Center*†Pennington Biomedical Research Center*University of Iowa*† Cincinnati Children’s Hospital Medical Center*†St. Claire Regional Medical CenterUniversity of Kansas*† Columbia University*†Seattle Children’s HospitalUniversity of Kentucky*† Duke University*†Stanford University*†University of Miami*† Louisiana State University A & M*Sutter West Bay HospitalsUniversity of New Mexico Health Sciences Center*† Indiana University*†Texas A&M University*University of North Carolina at Chapel Hill *† Louisiana State University HSC New Orleans*The Rockefeller University*†University of Pennsylvania*† Louisiana State University HSC Shreveport*The Scripps Research Institute†University of Pittsburgh*† Maine Medical Center*The University of Arizona*University of Southern California*† Marshall University*The University of Texas HSC at Houston*†University of Texas HSC at San Antonio*† Medical University of South Carolina*†The University of Utah*†University of Texas Southwestern Medical Center† Mayo Clinic*†Tufts Medical Center†University of Washington† Meharry Medical College†Tufts University †Vanderbilt University*† Michigan State University*Tulane University*Virginia Commonwealth University*† Mississippi State University*University of Alabama Birmingham*†Wake Forest University Health Sciences* Mount Sinai Medical School*†University of Arkansas for Medical Sciences*†Washington University (St. Louis) *† New York University School of Medicine*†University of California, Davis*†West Virginia University* North Shore LIH Health SystemUniversity of California, Los Angeles†*Xavier University (Louisiana) Northwestern University †University of California, San Diego† Ohio UniversityUniversity of California, San Francisco*†

10. Challenges (to all reliance models) Identifying studies 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)

11. Using IRBshare

12. Initiating Use of IRBshare 1.Identifying a Lead IRB ◦Naturally occurring (e.g., 1 st with IRB approval) ◦Select IRB based on experience, IRB willingness, site visit schedule 2.Investigator at Lead IRB approaches IRB ◦Request to use IRBshare and be Lead IRB ◦No change to submission process for investigator at Lead IRB 3.While the Lead IRB seeks approval… ◦Recruit non-IRBshare sites (ask Investigator at site to approach IRB) ◦IRBshare site investigators notify IRB liaison (here) and ask about submission procedures (e.g., short form application available?)here 4.Once Lead IRB has approval, sponsor/CRO/coordinating center disseminates approved documents to other study sites ◦Approved consent becomes model consent 5.Other site investigators insert local language into model consent and submit to their IRB as directed (see step 3)

13. Coordinating Use of IRBshare 1.Investigators at each site ONLY submit to their local IRB. 2.The investigator at the Lead IRB should always submit in a timely manner to their IRB 3.Initial Review: ◦The study should be submitted to the Lead IRB as soon as the protocol is finalized. All potential study sites do not have to be identified before the study is submitted for initial approval. ◦Study documents should be disseminated to the other sites as it would have without IRBshare. (e.g., a coordinating center or sponsor or clinical research organization (CRO), or the investigator if no coordinating mechanism exists) 4.Continuing Review: Lead investigators should submit at least 8 weeks prior to their expiration date to ensure the IRB has time to review, approve and upload it to IRBshare for other IRB’s to utilize to streamline their review. 5.Study-wide Amendments: Lead investigator submit as soon as the change is finalized and disseminate documents to other sites as soon as approval is received. (Note: amendments for safety reasons may need further discussion) 6.Local Amendments: do not get uploaded to IRBshare as they are site-specific and do not require review by each IRB, only the local IRB.

14. Industry-sponsor Registration IRBs not on project whitelist cannot access study documents IRBshare Admin adds sites to project per sponsor instruction