Use of Single IRBs for Multicenter Clinical Trials
For nearly a decade, CTTI has championed the adoption of single IRBs (sIRBs) for multicenter clinical trials. We have developed a number of recommendations and other resources to address barriers to and drive adoption of sIRB implementation.
Today, in light of recent mandated changes to the use of sIRBs in multicenter clinical trials, CTTI is building on past work by collaborating with an NIH workgroup to develop a comprehensive plan for assessing the NIH's sIRB policy. We are also developing resources to assist researchers and institutions in implementing the sIRB model.
Petra Kaufmann M.D., M.Sc. Director of the Division of Clinical Innovation at the 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 (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.
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 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.
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.
|Social Science Lead||Amy Cornelli||Clinical Trials Transformation Initiative||Single IRB Driving Adoption|
|Team Member||Andy Womack||Genentech - a member of the Roche Group||Single IRB Advancement|
|Team Member||Cami Gearhart||Quorum Review Inc||Single IRB Advancement|
|Team Member||Carol Pech||University of Wisconsin||Single IRB Driving Adoption|
|Team Member||Carrie Dombeck||Duke University||Single IRB|
|Team Member||Cheryl Grandinetti||Food and Drug Administration||Single IRB|
|Team Leader||Colleen Gorman||Pfizer Inc||Single IRB|
|Team Leader||Cynthia Hahn||Feinstein Institute for Medical Research||Single IRB Advancement|
|Team Member||Cynthia Hahn||Feinstein Institute for Medical Research||Single IRB|
|Team Member||Deneill Harney||University of Michigan||Single IRB Driving Adoption|
|Team Member||Devon Check||Duke University||Single IRB|
|Team Leader||Felix Gyi||Chesapeake IRB||Single IRB|
|Team Member||Hallie Kassan||Feinstein Institute for Medical Research||Single IRB Advancement/Driving Adoption|
|Team Member||James Riddle||Advarra Consulting||Single IRB Driving Adoption|
|Team Member||Jane Perlmutter||Individual Patient/Caregiver||Single IRB & Central IRB Advancement|
|Team Leader||Jennifer Li||Duke University||Single IRB|
|Team Member||Jennifer Peterson||Syneos Health||Single IRB Driving Adoption|
|Team Member||John Buse||NC TraCS, University of North Carolina at Chapel Hill||Single IRB Advancement|
|Team Member||Judith Kramer||Clinical Trials Transformation Initiative||Single IRB|
|Team Leader||Kathryn Flynn||Duke University||Single IRB|
|Team Leader||Kevin Weinfurt||Duke University||Single IRB|
|Team Member||Lawrence Muhlbaier||Duke University||Single IRB|
|Team Member||Margaret Rankovic||CITI Program, a Division of BRANY||Single IRB Driving Adoption|
|Team Member||Michael Link||Department of Veterans Affairs||Single IRB Driving Adoption|
|Team Member||Michele Russell-Einhorn||Advarra||Single IRB Driving Adoption|
|Team Member||Nichelle Cobb||University of Wisconsin||Single IRB Driving Adoption|
|EC Champion||Pat Furlong||Parent Project Muscular Dystrophy||Single IRB Driving Adoption|
|Team Member||Patrick Archdeacon||Food and Drug Administration||Single IRB|
|Team Member||Patrick McNeilly||Food and Drug Administration||Single IRB Advancement|
|Team Leader||Petra Kaufmann||National Institutes of Health||Single IRB Advancement|
|Team Member||Robert Silbergleit||University of Michigan||Single IRB Driving Adoption|
|Project Manager||Sara Calvert||Clinical Trials Transformation Initiative||Single IRB & Central IRB Advancement|
|Team Leader||Soo Bang||Celgene||Single IRB Advancement|
|Team Member||Yvonne Higgins||WIRB-Copernicus Group||Single IRB Advancement|