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 multi-center trials (i.e., a study that investigates a single research question at several different sites/locations), each site’s IRB (often referred to as local IRB) usually reviews the protocol separately. This can take a long time, cause duplicate work, and can 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, OHRP, and NIH, the willingness of institutions to defer full local IRB review and approval to a single IRB in multicenter trials continues to vary (Sources: FDA & OHRP). However, as of Jan. 25, 2018, the NIH mandates the use of a single IRB (sIRB) for NIH-funded multisite clinical trials. U.S. institutions engaged in cooperative research must rely on a single IRB for the portion of the research conducted in the U.S. when the single IRB provision of the revised Common Rule takes effect in January 2020. In addition, the U.S. FDA is revising their human subjects protection regulations and guidance because the 21st Century Cures Act modified the Federal Food, Drug and Cosmetic Act to remove the requirement for review by “local” institutional review committee for device studies and also requires harmonization of human subject protection regulations between the FDA and the rest of the federal government.

Since 2010, CTTI has worked to address challenges of adopting single IRB review and in 2017 evolved this work 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 single IRBs for multicenter clinical trials

• Using a single IRB 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 external central IRBs.
• Encouraging sponsors to utilize single IRBs in multi-center trials and providing them with CTTI tools to do so can increase their familiarity, comfort, and trust with using single IRBs for future trials.
• 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 to implement single IRB use in their trials and increase the number of institutes that utilize single IRBs.
• With more sponsors using a single IRB for multisite trials, study start-up will be accelerated and trial conduct will be improved, allowing treatments to reach patients faster.

The following methods were used to gather evidence for thi

• Literature review
• Stakeholder interviews
• Analyze 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 Apr. 25-26, 2012, Expert Meeting

Relating to the first Central IRB Project the literature review indicated that little empirical evidence existed on the use of central IRBs. The existing literature focused primarily on problems in efficiency 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 single IRB 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 a single IRB review, creating resistance to using single IRBs. 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 single IRB, 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, experts agreed that the definitions were 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 single IRBs to gain experience and trust. These solutions along with the definition of a central IRB, as a single IRB of record for multicenter clinical trials, and the clarification of responsibilities were recorded in the CTTI Recommendations.

Even with these tools, adoption of the use of a single IRB 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 single IRBs and confusion regarding how to implement the recommendations. To further facilitate adoption of single IRB use, CTTI issued new recommendations and several implementation tools, including an Evaluation Checklist, a Template IRB Authorization Agreement, and the revised Considerations Document.

As part of driving adoption activities, CTTI continues to engage stakeholders and investigate ways to ease the transition to single IRBs. In November 2017, CTTI convened an expert meeting to discuss further actions that CTTI, FDA, OHRP, and NIH can take to help the research community adopt single IRB review. Next steps from CTTI will involve new projects and smaller committees to develop additional supportive tools and strategies.

• Single IRB Policy for Multi-site Research, January 2018
• Final Revisions to the Common Rule, January 2017
• Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators by the HHS, July 2011
• 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)