The promise and perils of a single IRB in multi-center clinical trials: The PEPPER trial experience.

BACKGROUND: In 2016 the National Institutes of Health announced a new policy requiring single IRB (sIRB) use for multi-site human subjects research where the same protocol was used at all sites. A more efficient and consistent IRB review process was the goal without compromising ethical principles and protections. The PEPPER trial, a large multi-site comparative effectiveness trial, implemented sIRB prior to requirements for sIRB adoption. METHODS: The PEPPER clinical coordinating center critically reviewed study documents, protocol amendments, local sIRB implementation processes, benefits, liabilities, and performance and management differences between sIRB sites and those retaining local oversight. RESULTS: Lack of experience and availability of sIRB implementation tools lead to inefficient and varied practices. Median time for local site document completion in preparation for sIRB review was 161 days (n = 28; mean 188; range 45-429). Despite barriers, median overall time for clinical site onboarding was 174 days for sIRB sites (n = 28; mean 199; range 53-409) compared with 227 days (n = 4; mean 229; range 99-363) for sites retaining local IRB oversight. Efficiency of the amendment approval process was the most consistent and consequential benefit of sIRB, saving an estimated 189.5 days. CONCLUSIONS: Initial implementation of the PEPPER sIRB presented challenges with sites reluctant to cede authority, however our experience supports the benefit of improved efficiency and consistency when clinical sites cede reliance to a single central IRB in large multi center trials. Current federal mandates can be expected to reduce resistance to sIRB and start-up inefficiencies, and facilitate realization of the promise of the sIRB.