1. Supporting Single IRB Review within MidSouth CDRN

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

3. 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)

4. 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

5. 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 , 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.

6. 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

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

8. 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?

9. 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)

10. 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

11. Institutional Profiles

12. 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

13. Institutional Profiles

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

15. Capture and Track Reliance Requests

16. Study-specific Submission Instructions
Investigator Responsibilities and Submission Instructions Sheet

17. Central, Shared Document Repository

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

19. Using Single IRB Review with MidSouth

20. 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

21. CDRN Study-specific CIRB
PCORI
CDRN
CDRN Study-specific CIRB
IT Platform
Local Site/IRB
Study Team
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 s 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

22. WORKFLOW SLIDE