Use of Single IRBs for Multi-center 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 an 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 now working to explore new projects and committees to develop additional supportive tools and strategies for implementing sIRB review.
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 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
The following methods were used to gather evidence for thi
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 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|
|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|