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 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 a single IRB in multicenter trials continued to vary (Sources: FDA & OHRP).

However, as of January 25, 2018, the NIH mandates the use of a single IRB (sIRB) for multisite, nonexempt NIH-funded clinical studies. U.S. institutions engaged in cooperative federally funded research must rely on a sIRB for the portion of the research conducted in the U.S. when the sIRB provision of the revised Common Rule takes 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.

1. The Central IRB Project: “Use of Central IRBs for Multi-center Clinical Trials” (2010-2013)
2. Central IRB Advancement: “Advancing the Use of Central IRBs for Multi-center Clinical Trials” (2013–2015)
3. Single IRB Evaluation (2018 - ongoing)
4. Single IRB Adoption (2018 - ongoing)

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

• Using a 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
  • View materials from the Nov. 14, 2017, Expert Meeting
  • View materials from the June 12-13, 2014, Expert Meeting
  • View materials from the April 25-26, 2012, Expert Meeting

The literature review for the initial Central IRB Project indicated that little empirical evidence existed on the use of sIRBs. The existing literature focused primarily on inefficiencies associated with redundant local reviews of multicenter studies and the potential benefits of a centralized system.

A major finding from discussions with experts and stakeholder interviews was that many of the perceived barriers to using a sIRB of record arose from the fact that most of the tasks related to protecting the institution are often coordinated through the institution’s IRB office and incorporated into their review process. This leads to confusion about how institutional responsibilities would be handled in the context of sIRB review, creating resistance to using sIRBs. Also, an external entity handling the ethical review and oversight of a multicenter protocol creates discomfort for some sponsors. Finally, some experts felt that certain aspects important to IRB review could not be adequately addressed by a sIRB, since an outside group may not have necessary knowledge about the site’s unique local context.

Through expert meetings, it was apparent that clarification on the term “central IRB” was needed. Once it was defined as a single IRB of record for multicenter clinical trials, experts agreed that the definition was effective in clarifying the model of ethical review under consideration. Other solutions to barriers included decoupling institutional and ethical review responsibilities and encouraging more sponsors to use sIRBs to gain experience and trust. These solutions, along with the definition of a central IRB and the clarification of responsibilities, were recorded in the CTTI Recommendations. In 2014, the NIH released a draft policy referencing CTTI’s work and recommended the use of sIRBs to increase the efficiency of multicenter clinical trials.

Even with these tools, adoption of the use of a sIRB was slow. CTTI engaged with stakeholders during its Central IRB Advancement project to acquire feedback and identify and pose solutions to remaining barriers. There was a lack of trust and comfort with using sIRBs and confusion regarding how to implement the recommendations. To further facilitate adoption of sIRB use, CTTI issued new recommendations and several implementation tools, including an Evaluation Checklist, a Template IRB Authorization Agreement, and a revised Considerations Document.

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. The following year, 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. A driving adoption committee is developing additional supportive tools and strategies.

• 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)