Project:

Central IRBs

overview icon Overview

Use of Central IRBs for Multi-center Clinical Trials

Definition of a central IRB: CTTI defines a central Institutional Review Board (IRB) as a single IRB of record for all clinical trial sites in a multi-center trial.

Using a central IRB for multisite trials can improve the quality and efficiency of multi-center clinical trials. The US Food and Drug Administration (FDA) and Office of Human Research Protections (OHRP) have both encouraged the use of a single, central IRB for multi-center trials and CTTI issued recommendations and a Considerations document in 2013 to address barriers to the adoption of central IRBs for multi-center clinical trials (Sources: FDA & OHRP). Despite this, many research sites are still hesitant to use a single, central IRB. Therefore, CTTI sought to identify potential solutions that address the initial and remaining barriers to the adoption of central IRBs for multi-center clinical trials with the hope of increasing the number of institutions that use central IRBs, assisting with study start-up and drug approvals progressing more quickly.

CTTI identified several barriers to central IRB adoption including 1) a general misunderstanding of the definition, role, and responsibilities of central IRBs, 2) lack of experience or familiarity with the process for using a central IRB, and 3) difficulties with learning how to use of central IRBs. One of the main barriers to using central IRBs is that local sites use IRBs not only for approving protocols, but also for various site-specific tasks related to clinical trials, such as training staff, making sure investigators comply with research protocols, and making sure HIPAA privacy rules are being followed. To advance the use of central IRBs, CTTI analyzed feedback from stakeholders and developed new recommendations, an Evaluation Checklist, and a Template IRB Authorization Agreement.

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Discover Additional Deliverables Generated From This Project

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 <br/>National Center for Advancing Translational Sciences (NCATS), NIH

On December 3, 2014, the National Institutes of Health issued a draft policy for the use of single IRBs in multi-site clinical research studies, citing a CTTI publication.

“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 to this would be for all of the sites in a multi-center trial to use the same IRB (a central IRB). Although central IRB use is supported by the US FDA and OHRP, the willingness of institutions to defer full local IRB review and approval to a central IRB in multi-center trials continues to vary (Sources: FDA & OHRP).

Sponsors indicated that several challenges to adopting central IRB use still existed (see Findings). Specifically, there was still a lack of comfort and trust using a central IRB, and there were concerns regarding administration and the ability of the central IRB to address issues related to the local context of research.

  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 single IRB of record for multi-center clinical trials
  • To propose solutions, recommendations, and tools to advance the use of central IRBs for multi-center clinical trials
  • Using a central IRB for a multi-center 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 central IRBs in multi-center trials when possible and providing them with CTTI tools to do so can increase their familiarity, comfort, and trust with using central 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 central IRB use in their trials and increase the number of institutes that utilize central IRBs.
  • With more sponsors using a central 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 this project.

  • Literature review
  • Stakeholder interviews
  • Analyze IRB Authorization Agreements and SOPs
  • Case examples
  • Expert meetings and workshops
    • CLICK HERE to view materials from the June 12 - 13, 2014 Expert Meeting
    • CLICK HERE to view materials from the April 25 - 26, 2012 Expert Meeting

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 central IRBs 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 central IRB review, creating resistance to using central 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 central 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 (see definition and a longer definition described in the Project Summary), 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 central IRBs to gain experience and trust. These solutions along with the definition of a central IRB and the clarification of responsibilities were recorded in the and CTTI Recommendations. Even with these tools, adoption of the use of a central IRB was slow. CTTI engaged with stakeholders to acquire feedback and identify and pose solutions to remaining barriers. There was a lack of trust and comfort with using central IRBs and confusion regarding how to implement the recommendations. To further facilitate adoption of central IRB use, CTTI issued new recommendations and several implementation tools, including an Evaluation Checklist, a Template IRB Authorization Agreement, and the revised Considerations Document.

Project Team Members

Rolesort descending Name Affiliation Project
Project Manager Sara Calvert CTTI Central IRB & Central IRB Advancement
Team Leader Cynthia Hahn Feinstein Institute for Medical Research Central IRB Advancement
Team Leader Petra Kaufmann National Institutes of Health Central IRB Advancement
Team Leader Jennifer Li Duke University Central IRB
Team Leader Kevin Weinfurt Duke University Central IRB
Team Leader Soo Bang Celgene Central IRB Advancement
Team Leader Kathryn Flynn Duke University Central IRB
Team Leader Colleen Gorman Pfizer Inc Central IRB
Team Leader Felix Gyi Chesapeake IRB Central IRB
Team Member Patrick Archdeacon Food and Drug Administration Central IRB
Team Member John Buse NC TraCS, University of North Carolina at Chapel Hill Central IRB Advancement
Team Member Devon Check Duke University Central IRB
Team Member Carrie Dombeck Duke University Central IRB
Team Member Cami Gearhart Quorum Review Inc Central IRB Advancement
Team Member Cheryl Grandinetti Food and Drug Administration Central IRB
Team Member Cynthia Hahn Feinstein Institute for Medical Research Central IRB
Team Member Yvonne Higgins WIRB-Copernicus Group Central IRB Advancement
Team Member Hallie Kassan Feinstein Institute for Medical Research Central IRB Advancement IRB
Team Member Judith Kramer Clinical Trials Transformation Initiative Central IRB
Team Member Patrick McNeilly Food and Drug Administration Central IRB Advancement
Team Member Lawrence Muhlbaier Duke University Central IRB
Team Member Jane Perlumtter Individual Patient/Caregiver Central IRB & Central IRB Advancement
Team Member Andy Womack Genentech-a member of the Roche Group Central IRB Advancement