Pressure Mounts for Central IRBs

Efforts are escalating to encourage sponsors, research institutions and clinical investigators to accept oversight for multi-center studies by central Institutional Review Boards (IRBs), as seen in several discussions of this topic at the December conference on “Advancing Ethical Research” sponsored by PRIM&R (Public Responsibility in Medicine & Research). The debate was heightened by the recent publication by the National Institutes of Health (NIH) of a draft policy promoting the use of central IRBs to make clinical trials more efficient. While regulatory officials, sponsors and investigators acknowledged that oversight by multiple IRBs often is redundant, costly and time-consuming, there remains reluctance by local sites and research organizations to hand the reins to others.

The proposed NIH guide “On the Use of a Single Institutional Review Board for Multi-Site Research,” issued Dec. 3, 2014, encourages participants in multi-site NIH-funded studies to use a single IRB of record. “Working through IRB review at each site can add delay without increasing the protections for research participants,” NIH stated, noting that the National Cancer Institute (NCI) has had a central IRB in place since 1999, and other NIH Institutes have followed suit. NCI continues to encourage (but not require) investigators to utilize its CIRB review to reduce the administrative burden on local IRBs and investigators and to provide high-level protection for study participants. The new NIH policy acknowledges that foreign sites may not agree to central oversight, and that some exceptions may be appropriate.

Similarly, NIH’s Clinical and Translational Science Awards (CTSA) program, which supports a large network of research sites across the country, is promoting the use of central IRBs for the review of multi-site research as part of its program to spur development of biomedical discoveries into new therapies. Patients are frustrated by the slow pace of clinical research and delays in trial start-up, noted Petra Kaufmann, director of the division of clinical innovation at NIH’s National Center for Advancing Translational Sciences (NCATS). She observed at the PRIM&R conference that the use of local IRBs at each site can delay study initiation, and that CTSA’s IRB Reliance Project is looking to develop harmonized practices, integrated IT models and standard reliance agreements that will lead to the adoption of common procedures at multiple research organizations.

Kaufmann also is involved in the Central IRB Advancement project of the Clinical Trials Transformation Initiative (CTTI), an FDA-supported public-private partnership that is developing a guide for using central IRBs to encourage more sponsors to require this approach for their clinical programs. Many biopharmaceutical companies already use central commercial IRBs to oversee multiple sites participating in studies designed to support market registration of new drugs and biologics, a process supported by FDA guidance published in 2006. Further development of data sharing templates and oversight agreements can support these efforts and encourage investigators to use a designated central IRB in order to participate in sponsored trials.

There was further discussion at the PRIM&R conference on the spectrum of streamlined IRB models, ranging from information-sharing, to federations, to fully centralized programs. NIH officials and others discussed how they are testing whether and how central IRB models can accelerate trial start-up and completion. Regional coalitions in California, Texas, New England and other states are developing and adopting IRB agreements that encourage reliance of local institutions on others but raise the risk that each coalition will implement different policies and standards that could stymie broader common approaches.

NIH has been accepting comments on its December central IRB proposal and hopes to issue a final policy by mid-year, setting the stage for implementation in 2016. Local research organizations fear that a reduced role in overseeing research could raise liability issues, require changes in administrative procedures, and limit consideration of important local issues. But pressure to conserve resources and accelerate research are expected ultimately to drive adoption of single-IRB review models.