Streamlining regulatory review in a multicenter platform trial: Opportunity to enhance patient centered care and drive innovation and efficiency.
Authors: Colley Alexis , Helsten Teresa L. , Moore Brian , Neuhauser Linda , LeStage Barbara Keenoy , Castillo Paolo , Pitsiouni Maria , Elias Anthony D. , Falkson Carla Isadora , Thomas Alexandra , Isaacs Claudine , Clark Amy Sanders , Potter David , Roussos Torres Evanthia T. , Nanda Rita , Nangia Chaitali , Esserman Laura 
Published: June 2023

1572

Background: In addition to being required by the Federal Policy for the Protection of Human Subjects for United States-based institutions that receive federal funding and are engaged in cooperative research projects, the use of a central Institutional Review Board (cIRB) has multiple benefits. Yet more advanced trial designs have unique needs and challenges that may hinder adoption of an efficient cIRB. Platform trials, which require both a master protocol and successive individual protocol amendments for each new agent, are prone to high regulatory burden that can slow trial recruitment, representing a significant workload for study personnel. Specific challenges for platform trials include high burden of new amendments and IRB review schedules staggered across sites, making it challenging to have all sites operating under the same amendment concurrently. Methods: Administrative assessments were collected over the course of the I-SPY2 trial. The primary outcome of interest was time from amendment submission to approval (calculated as the number of days from submission to the local IRB by the site investigators to approval by the local IRB). Quantitative data in terms of hours spent on regulatory tasks pre- and post-cIRB implementation was estimated. Site investigators were asked in December 2022 to complete a brief questionnaire to investigate perceptions on changes to workload and level of comfort using a cIRB. Results: Amendments were activated when 50% of high accruing sites had IRB approval. The number of sites with approval for an amendment to go live was < 25% prior to cIRB adoption, and 83% after. Following transition to the cIRB in February 2021, the mean time from amendment submission to approval decreased from 54.4 to 20.7 days by Jan 2023. Changes to the informed consent were possible once the cIRB was adopted, including: standardizing site-specific IRB language in a section of the consent, so it need not be adjusted with every new agent amendment; standardizing site-specific workflows; shortening consent and making it more patient friendly. The average time that CRCs spent on regulatory work at each site decreased by an average of 160 minutes, but was variable, revealing continued use of local IRB, other committees at some sites. A total of 14 respondents completed the survey; most respondents indicated that keeping up with the amendment approval process was easier post-cIRB and 94% were comfortable relying on a cIRB. The short time for cIRB approval revealed the inefficiency of other processes, including coverage analysis and building of drug order sets. Conclusions: Active engagement of cIRB leadership and IRB working group has enabled regulatory review that now takes less than 30 days. The cIRB is now the standard for the I-SPY family of trials. Other services can also be shared and will continue to drive efficiency and reduce the regulatory burden for sites.