One of the Recognized Barriers to Conducting Multi-Site Studies Is Acquiring Institutional

One of the recognized barriers to conducting multi-site studies is acquiring Institutional Review Board (IRB) approval from each engaged research site. The IRB review of multisite studies has been constrained by well-known and increasingly publicized process-related inefficiencies, questions about the value of redundant reviews, and concerns about variability in outcome. To avoid these issues and maximize efficiency and consistency across study sites, we will utilize a central IRB process to streamline the IRB review of this study. While many cIRB arrangements exist regionally, there are two national options, IRBchoice and SMART IRB. IRBchoice is a national IRB reliance platform funded by the National Heart Lung and Blood Institute (NHLBI) (Grant #1R01HL126492-01) at Vanderbilt University Medical Center. IRBchoice has a single Institutional Master Agreement (IMA) which allows participating institutions to both serve as the single IRB or cede IRB review to another participating institution’s IRB. SMART IRB is also a national IRB reliance agreement with a similar single IMA. Both agreements contain many features that will aid the acceptance, coordination, and implementation of a single IRB review model in a highly cost effective manner, including:

1. Single IRB Review. Most academic medical centers utilize many different reliance agreements for single IRB review. For thisnetwork,Vanderbilt’s IRB will serve as the Lead IRB (see Letter of Support) for all institutions using IRBchoice, SMART IRB, or other mutually agreed upon reliance agreement. Other institutions will cede review to the Vanderbilt cIRB through one of these reliance agreements so that all study sites having the same IRB determination, consent template(s), and expiration date.
2. Master Reliance Agreement. All institutions in IRBchoice and/or SMART IRB sign a one-time master reliance agreement to support reliance on any multi-site study between member institutions. Many of the chosen participating sites will already be members of either IRBchoice or SMART IRB, signaling high acceptability. Participating sites which are not already members of one of the national reliance agreements will be encouraged to join one of the agreements for purposes of ceding IRB review to the Vanderbilt cIRB. The executed master reliance agreements will allow us to avoid the approximate 6 to 12 month delay negotiating a new, study-specific reliance agreement.
3. National Reliance Network: IRBchoice and SMART IRB are both open to any US institution with an FWA and are free to join. Currently there are over 100institutional partners already signed up to one or both agreements.
4. Informatics Platform: The IRBchoice and SMART IRB informational technology platforms foster communication and transparency between participating IRBs, which are two critical factors forensuring compliance when using a single IRB review. Moreover, both provide notifications regarding new approvals and impending expirations to ensure study compliance and consistency across study sites.
5. Investigator Support and Coordination:A critical element of single IRB review is study coordination across sites and ensuring investigators and studyteams understand their responsibilities. Unfortunately, in the absence of a national IRB submission system, single IRB review does not mean only one IRB is involved in the approval of the study, nor does it mean that investigators only report and submit to a single IRB. Each institution and site investigator retains their responsibility for the conduct of research at their site. As such, investigators at relying sites must submit at least minimal information to their local IRB for review. Independent reviews of each site’s local context (e.g., consent form contains locally required language for HIPAA, subject injury language, conflict of interest, etc.) and “non-IRB” institutional reviews (institutional biosafety, radiation safety, investigator education and training, conflict of interest, etc.) must be performed by each institution, if applicable. To ensure compliance and that each investigator understands to whom they submit and report specific information, the IT platforms provide study-specific submission and reporting instructions for study investigators. Additionally, the systems provide real-time notifications of approval from the Lead IRB, as well as notices of approaching expirations.
6. Vanderbilt sIRB Team: As part of the Vanderbilt sIRB efforts, an sIRB team has been developed. This sIRB team is responsible for collecting local context information from participating sites, ensuring that consent forms contain appropriate local language where applicable, assisting with submission of applications, amendments, protocol violations, adverse events, and continuing reviews as well as federal regulatory documentation, and interacting with local IRB officials at participating sites.