Before a clinical trial begins, the study protocol needs to be reviewed by an impartial third party (usually an IRB) to ensure ethical rigor and to determine that the study provides potential benefits and prevents unnecessary harm to participants. In a multicenter trial (i.e., a study that investigates a single research question at several different sites/locations), each site’s IRB (often referred to as a local IRB) usually reviews the protocol separately. This can take a long time, cause duplicate work, and even result in the protocol being changed by individual sites so that it is no longer the same across all sites.

One solution is for all sites in a multicenter trial to use the same IRB (a single IRB of record). Although single IRB (sIRB) review is supported by the FDA, the Office of Human Research Protections (OHRP), and the NIH, the willingness of institutions to defer full local IRB review and approval to an sIRB in multicenter trials continued to vary (Sources: FDA & OHRP).

However, as of January 25, 2018, the NIH mandates the use of an sIRB for multisite, nonexempt NIH-funded clinical studies. U.S. institutions engaged in cooperative federally funded research must rely on an sIRB for the portion of the research conducted in the U.S. since the sIRB provision of the revised Common Rule took effect in January 2020. In addition, the FDA is revising its human subjects protection regulations and guidance because the 21st Century Cures Act required harmonization of human subjects protection regulations between the FDA and the rest of the federal government and modified the Federal Food, Drug, and Cosmetic Act to remove the requirement for review by local institutional review committees for device studies.

Since 2010, CTTI has worked to address challenges of adopting sIRB review. In 2018, this work evolved to focus on supporting adoption of sIRB models.

• The Central IRB Project: “Use of Central IRBs for Multi-center Clinical Trials” (2010-2013)
• Central IRB Advancement: “Advancing the Use of Central IRBs for Multi-center Clinical Trials” (2013-2015)
• Single IRB Adoption (2017 - 2019)
• Single IRB Evaluation (2018 - 2019)

• To identify and address barriers to using an sIRB of record for multicenter clinical trials
• To propose solutions, recommendations, and tools to advance the use of sIRBs for multicenter clinical trials

• Using an sIRB for a multicenter trial will improve trial efficiency and consistency.
• Use of the Considerations Document will help delineate the legal and ethical responsibilities of institutions and IRBs in overseeing the conduct of clinical trials and can support communication between institutions and sIRBs.
• Use of the CTTI-developed tools (including the Considerations Document, an Evaluation Checklist, and a Template IRB Authorization Agreement will make it easier for sponsors, IRBs, and institutions to implement the sIRB model for multisite research.
• With widespread use of the sIRB model for multisite trials, study start-up will be accelerated and trial conduct will be improved, allowing treatments to reach patients faster.

• Literature review
• Stakeholder interviews
• Analysis of IRB Authorization Agreements and SOPs
• Case examples
• Expert meetings and workshops
  • Nov. 14, 2017, Expert Meeting
  • June 12-13, 2014, Expert Meeting
  • April 25-26, 2012, Expert Meeting

As part of driving adoption activities, CTTI continues to engage stakeholders and investigate ways to ease the transition to sIRBs. In November 2017, CTTI convened an expert meeting to discuss further actions that CTTI, the FDA, the OHRP, and the NIH can take to help the research community adopt sIRB review. In 2018, the NIH selected CTTI to support a workgroup that will develop a comprehensive plan for assessing the effectiveness of the NIH’s new sIRB policy. In September 2019, a CTTI driving adoption committee developed a set of new resources, including an Engagement Overview, Engagement Flowchart, Engagement Scenarios Guide, Engagement Definitions, and a Resource of Resources library.

• Single IRB Policy for Multi-site Research, January 2018
• Final Revisions to the Common Rule, January 2017
• The Paradoxical Problem with Multiple-IRB Review, New England Journal of Medicine, October 2010
• OHRP Public Correspondence on Central IRBs by the OHRP, April 2010
• Guidance for Industry: Using a Centralized IRB Review Process in Multicenter Clinical Trials by the FDA, 2006 (July 31, 2012)

Organization affiliations are listed as active affiliations during the project.

*Indicates former project manager, team leader, or team member.