Project:

Single IRB

overview icon Overview

Use of Single IRBs for Multicenter Clinical Trials

Using a single IRB (sIRB) for multisite trials can improve the quality and efficiency of multicenter clinical trials. Since 2010, CTTI has worked to address barriers to the adoption of sIRB for multicenter clinical trials, developing recommendations, a considerations document, and many other resources for the enterprise. In 2014, the National Institutes of Health (NIH) released a draft policy referencing CTTI’s work and recommended the use of sIRBs to increase the efficiency of multicenter clinical trials. Then, in 2016, the NIH issued a final policy requiring the use of a sIRB for multicenter NIH-funded clinical trials effective Jan. 25, 2018. In 2017, the final changes to the Common Rule were announced, including a mandate that U.S. institutions involved in cooperative research in the U.S. (with certain exceptions) use a sIRB, effective Jan. 20, 2020.

CTTI is now exploring further actions that it, the FDA, OHRP, and NIH can take to help the research community adopt sIRB review. In November 2017, CTTI held an expert meeting with the goal of identifying remaining gaps in knowledge and potential solutions to implementing a sIRB model. There, representatives from academia, government agencies, IRBs, pharmaceutical and device companies, contract research organizations, and patient groups, identified remaining gaps in knowledge and potential solutions to implementing a sIRB model.

CTTI is also working to explore new projects and committees to develop additional supportive tools and strategies for implementing sIRB review.

quick links icon Quick Links to Top Deliverables

Discover Additional Deliverables Generated From This Project

Tool

Template IRB Authorization Agreement (IAA): Intended to address an administrative concern about using a single central IRB

Webinar

NIH Collaboratory Grand Rounds on Advancing the Use of Central IRBs for Multi-center Trials by Cynthia Hahn

Expert Meeting Materials

Materials, including the executive summary and presentations, from the Expert Meeting held on June 12 - 13, 2014

Webinar

Research Institution Perspectives on Advancing the Use of Central IRBs for Multi-center Clinical Trials in the United States

Webinar

Sponsors' Perspectives on Advancing the Use of Central IRBs for Multi-center Clinical Trials in the United States

Presentation

An Update on the CTTI Use of Central IRBs for Multi-center Clinical Trials Project - Presented November 2013 at the PRIM&R 2013 Advancing Ethical Research Conference

External Communications

Blog Post by BIOTechNOW: CTTI: use of central IRBs in multi-center trials to streamline clinical research

Publication

Check DK, Weinfurt KP, Dombeck CB, Kramer JM, Flynn KE. Use of central institutional review boards for multi-center clinical trials in the United States: A review of the literature. Clin Trials. 2013; 10(4): 560-567.

Publication

Flynn KE, Hahn CL, Kramer JM, Check DK, Dombeck CB, Bang S, Perlmutter J, Khin-Maung-Gyi FA, Weinfurt KP. Using central IRBs for multi-center clinical trials in the United States. PLoS One. 2013; 8(1): e54999.

Press Release

Conducting Multi-Center Trials: New Recommendations and Tool for Research

Project Report

Final Report of CTTI's first Central IRB Project

Poster

Use of Central IRBs for Multi-center Clinical Trials - Presented December 2012 at the PRIM&R 2012 Advancing Ethical Research Conference

Expert Meeting Materials

Materials, including the executive summary and presentations, from the Expert Meeting held on April 25-26, 2012

“Using a single IRB for multi-site clinical research is an important step in accelerating the translation from discoveries to health benefits. The Clinical and Translational Science Awards (CTSA) program is working toward using a single IRB for multi-site studies. The CTTI Central IRB recommendations will be very helpful in advancing towards this goal.”

Petra Kaufmann M.D., M.Sc. Director of the Division of Clinical Innovation at the National Center for Advancing Translational Sciences (NCATS), NIH

On December 3, 2014, the National Institutes of Health (NIH) issued a draft policy for the use of single IRBs in multi-site clinical research studies, citing a CTTI publication. The final NIH policy and single IRB mandate went into effect Jan. 25, 2018.

“The National Cancer Institute is moving toward the NCIRB being the sole IRB of record and we are starting to see many sponsors require central IRB review as more institutions are coming on board and becoming comfortable with the model.”

Cynthia Hahn Chief Operating Officer, Feinstein Institute for Medical Research

"We implemented the CTTI recommendations within our company and made a commitment that all sponsors of clinical trials would be reviewed by a central IRB.”

Soo Bang Senior Director, Business Development and Global Alliances, Celgene Corporation

“We think that there is a lot of merit in supporting improvements in the clinical trial infrastructure itself. The Clinical Trials Transformation Initiative has contributed so much in terms of innovative trial design, as it is working on establishing centralized IRBs for multicentered trials, which is an important advancement.”

Margaret A. Hamburg, MD former Commissioner, FDA

Page 1 Project Progress

Identify Research Impediments
100%
Gather Evidence
100%
Analyze & Interpret Findings
100%
Develop Recommendations
100%
Disseminate & Implement
100%

in detail icon In Detail

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)
  • 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.

Project Team Members

Rolesort descending Name Affiliation Project
Project Manager Sara Calvert Clinical Trials Transformation Initiative Single IRB & Central IRB Advancement
Social Science Lead Amy Cornelli Clinical Trials Transformation Initiative Single IRB Driving Adoption
Team Leader Kathryn Flynn Duke University Single IRB
Team Leader Colleen Gorman Pfizer Inc Single IRB
Team Leader Felix Gyi Chesapeake IRB Single IRB
Team Leader Cynthia Hahn Feinstein Institute for Medical Research Single IRB Advancement
Team Leader Petra Kaufmann National Institutes of Health Single IRB Advancement
Team Leader Jennifer Li Duke University Single IRB
Team Leader Kevin Weinfurt Duke University Single IRB
Team Leader Soo Bang Celgene Single IRB Advancement
Team Member Andy Womack Genentech - a member of the Roche Group Single IRB Advancement
Team Member Petrice Brown-Longenecker National Institutes of Health Single IRB Driving Adoption
Team Member John Buse NC TraCS, University of North Carolina at Chapel Hill Single IRB Advancement
Team Member Devon Check Duke University Single IRB
Team Member Nichelle Cobb University of Wisconsin Single IRB Driving Adoption
Team Member Carrie Dombeck Duke University Single IRB
Team Member Emily Eldh Dana-Farber Cancer Institute Single IRB Driving Adoption
Team Member Cami Gearhart Quorum Review Inc Single IRB Advancement
Team Member Cheryl Grandinetti Food and Drug Administration Single IRB
Team Member Cynthia Hahn Feinstein Institute for Medical Research Single IRB
Team Member Denell Harney University of Michigan Single IRB Driving Adoption
Team Member Yvonne Higgins WIRB-Copernicus Group Single IRB Advancement
Team Member Hallie Kassan Feinstein Institute for Medical Research Single IRB Advancement/Driving Adoption
Team Member Judith Kramer Clinical Trials Transformation Initiative Single IRB
Team Member Michael Link Department of Veterans Affairs Single IRB Driving Adoption
Team Member Patrick McNeilly Food and Drug Administration Single IRB Advancement
Team Member Lawrence Muhlbaier Duke University Single IRB
Team Member Carol Pech University of Wisconsin Single IRB Driving Adoption
Team Member Jane Perlmutter Individual Patient/Caregiver Single IRB & Central IRB Advancement
Team Member Jennifer Peterson Syneos Health Single IRB Driving Adoption
Team Member Margaret Rankovic CITI Program, a Division of BRANY Single IRB Driving Adoption
Team Member James Riddle Quorum Review IRB Single IRB Driving Adoption
Team Member Michele Russell-Einhorn Advarra Single IRB Driving Adoption
Team Member Patrick Archdeacon Food and Drug Administration Single IRB
Team Member Robert Silbergleit University of Michigan Single IRB Driving Adoption