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.
Petra Kaufmann M.D., M.Sc. Director of the Division of Clinical Innovation at the <br/>National Center for Advancing Translational Sciences (NCATS), NIH
“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.”
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.
Cynthia Hahn Chief Operating Officer, Feinstein Institute for Medical Research
“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.”
Soo Bang Senior Director, Business Development and Global Alliances, Celgene Corporation
"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.”
Margaret A. Hamburg, MD former Commissioner, FDA
“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.”
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.
The following methods were used to gather evidence for this 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 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 Manager||Sara Calvert||CTTI||Central IRB & Central IRB Advancement|
|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 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 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|