Supporting Single IRB Review within MidSouth CDRN

A Brief History of Single IRB Review The Evolution of Single IRB Review Models

Decentralized IRB Review of Multi-site Studies Burdensome (Helfand, et al., 2009) Inefficient (Greene & Geiger, 2006; Greene, Geiger, & Harris, 2006; Sherwood, et al., 2006) Duplicative (Burman, Reves, Cohn, & Schooley, 2001) Require substantial portions of grant awards (Vick, Finan, Kiefe, Neumayer, & Hawn 2005) Can delay or prevent study activation (Helfand, et al., 2009) Insufficiently protect human subjects (Menikoff, 2010)

Evolution of OHRP and FDA Policy Select Calls for Streamlined IRB Review Model Creation and Use 2005: OHRP, AAMC, ASCO, NIH, and VA workshop report recommended development of responsibilities of alternative review mechanism and consideration of local IRB responsibilities 2006: FDA guidance on “Using a centralized IRB review process in multicenter trials” recommended centralized IRB review process should include meaningful consideration of relevant local factors 2008: SACHRP letter to HHS Secretary encouraged letter to NIH Director to explore greater use of collaborative IRB review models 2010: OHRP Director notes that sponsors could require use of central IRBs (CIRBs) 2011: NCRR (now: NCATS) funds R13 that leads to develop IRBshare (Vanderbilt, PI-Bernard) DHHS releases ANPRM calling for a single IRB for multisite studies 2012: NINDS’s launches NeuroNEXT CIRB 2013: NCI requires use of NCI CIRB for certain studies NINDS RFA encouraged “‘shared review’ such as IRBshare or a CIRB” in rare disease NHLBI funds PETAL network seeking collaborative/central/shared IRB 2014: NINDS’s launches StrokeNET CIRB NCATS funds development of national IRB Reliance Agreement NHLBI funds R01 for IRBchoice (Vanderbilt, PI-Rice) NIH proposes policy requiring use of a single IRB of record for all NIH-funded studies 2015: DHHS releases NPRM calling for single IRB for multisite studies

Recent NIH Policy on Use of a Single IRB (sIRBs) The National Institutes of Health (NIH) Policy on the Use of a Single Institutional Review Board of Record for Multi- Site Research establishes the expectation that all sites participating in multi- site studies involving non-exempt human subjects research funded by the National Institutes of Health (NIH) will use a single Institutional Review Board (sIRB) to conduct the ethical review required by the Department of Health and Human Services regulations for the Protection of Human Subjects at 45 CFR Part 46.  This policy, which is consistent with 45 CFR Part 46.114, is intended to enhance and streamline the process of IRB review and reduce inefficiencies so that research can proceed as expeditiously as possible without compromising ethical principles and protections for human research participants. Consistent with the Roles and Responsibilities section, applicants/offerors will be expected to include a plan for the use of an sIRB in the applications/proposals they submit to the NIH.  The NIH’s acceptance of the submitted plan will be incorporated as a term and condition in the Notice of Award or in the Contract Award.  This policy also applies to the NIH Intramural Research Program. This policy applies to all competing grant applications (new, renewal, revision, or resubmission) with receipt dates on or after May 25, 2017.  Ongoing, non-competing awards will not be expected to comply with this policy until the grantee submits a competing renewal application.  For contracts, the policy applies to all solicitations issued on or after May 25,, 2017.  For the intramural program, the policy applies to intramural multi-site studies submitted for initial review after May 25, 2017.

SINGLE IRB REVIEW = SINGLE IRB REVIEW Review of investigator training and expertise Ancillary Reviews (pharmacy, COI, radiation, biosafety) Monitoring compliance with local, state laws; HIPAA Institutional Resources Review Grants and Contracts Initial/new study Continuing review Amendments to the study Local changes (changes to funding, key study personnel) Potential unanticipated problems

Implementing a Single IRB for the MidSouth CDRN Taking advantage of existing infrastructure

The Reliance Agreement Study-specific Reliance Agreements Clear delineation of responsibilities Limited scalability Regional + Consortium-specific Reliance Agreements Reduced duplication of effort Familiarity Exclusivity Master Reliance Agreements Minimal duplication of effort Significant scalability Operationalizing study-specific logistics Trust What works?

SMART IRB Reliance Agreement Supported by NCATS supplement to Harvard Barbara Bierer Sabune Winkler Nichelle Cobb Open to any institution with an FWA Training on the agreement Will be used to support the Trial Innovation Centers’ CIRBs (Utah, Vanderbilt, and Johns Hopkins)

Trial Innovation Center Regulatory Review System (TIC-RR) Maintained by Vanderbilt; built off the IRBchoice platform Platform primarily supports IRB communication and documentation of approval Platform is not a submissions system—each Reviewing/Lead/CIRB will use their existing submission system to collect studies/information for IRB review Coordinating Center and Study Team Portals are being added by early 2017

Institutional Profiles

Institutional Profiles About your HRPP About your local context About your workflow/submission requirements when you are the Relying Site About your reliance preferences when you are the IRB of Record for others

Institutional Profiles

Centralized Single IRB Requests Funding source Resources for single IRB review Study coordination Participants Study procedures Institutions involved (# + type)

Capture and Track Reliance Requests

Study-specific Submission Instructions Investigator Responsibilities and Submission Instructions Sheet

Central, Shared Document Repository

Email Notifications for approvals, amendments, and expirations Confirmation of Ceded Review and Reliance

Using Single IRB Review with MidSouth

Process for Initiating Single IRB Review IRBs Study Teams Coordinating Centers Identify and Confirm a Lead IRB Overall study PI Site identified by funder/sponsor First site to receive IRB approval Based on study procedures Notify relying sites (PIs + IRBs) Execute reliance agreement Agree to cede review in IRBchoice Disseminate relying investigator instructions Submit relying site study info to Lead IRB CC Lead IRB Study Team

CDRN Study-specific CIRB PCORI CDRN CDRN Study-specific CIRB IT Platform Local Site/IRB Study Team Email site (IRB + Team) SMART IRB agreement Site signs SMART IRB? No Site does not cede review Yes Study approved by PCORI, if applicable CDRN IRBs identify CIRB for study No CIRB creates study in IT platform IT platform emails site IRBs about study + CIRB Site signed SMART IRB? Site reviews study + cede review No Yes Yes IT platform notifies CIRB that site agreed to cede review Local site notes decision to cede review in IT platform Initial Study Approval Study team submits to local IRB, as instructed IT Platform notifies local study team re: local + CIRB submission instructions CC/CIRB Investigator submits to CIRB for approval Local site notes verification of local context + approval to submit to CIRB Local site/IRB reviews study CIRB review + approve study CIRB uploads approved doc + approval metrics IT platform notifies sites (IRBs + Study Teams) of approval Study team initiates study

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