IRBshare: Streamlining IRB Review of Multisite Studies

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) ( ) *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

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 ) 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

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

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

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

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

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

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*†

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)

Using IRBshare

Coordinating Use of IRBshare 1.Identifying a Lead IRB ◦Naturally occurring (1 st with IRB approval) ◦Select IRB based on experience, IRB willingness, site visit schedule 2.While Lead IRB seeking approval ◦Recruit non-IRBshare sites ◦Site investigators notify IRB of study + IRBshare; inquire about submission procedures 3.Once Lead IRB has approval, disseminate approved documents to other study sites ◦Approved consent becomes model consent 4.Site investigators submit (initial, continuing and amendment reviews) and report (adverse events) to the local IRB following local submission policies ◦Local IRB uses streamlined review to approve ◦Follow study protocol/direction from sponsor when reporting serious adverse events

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