RESUMEN
Introduction: As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring. Methods: The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed. Results: Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial's DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report. Conclusion: It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMBc and will help expand these initiatives so DSMBs may make more informed decisions with all available information.
RESUMEN
For decades, the research community called for streamlined Institutional Review Board (IRB) review processes for multisite studies. Department of Health and Human Services and National Institutes of Health (NIH) recognized this need and implemented single IRB (sIRB) of record mandates. However, announcing mandates without sufficient operational guidance and tools is insufficient to foster the desired change. Nearly 4 years into implementation of the NIH's sIRB mandate, operational challenges remain. Fortunately, NIH supports a web-based sIRB platform, the IRB Reliance Exchange (IREx), to facilitate sIRB communication and documentation. IREx has received continuous NIH funding supporting its evolution since 2011 and is now used by over 5,000 Human Research Protection Program and research personnel, 35 sIRBs, and 415 participating sites to operationalize sIRB review and approval on over 400 studies. IREx supports over 2300 reliance relationships with an average of 7 sites per study. The platform is continually used by sIRBs and relying sites, providing a valuable centralized portal for promoting a harmonized sIRB review process. IREx can promote transparency, standardize practice, minimize workflow variation, and mitigate the need for sIRBs to implement significant technical changes to their local electronic systems. IREx has proven to be nimble and adaptable with practice and policy changes over the past decade, as evidenced by continually increasing platform utilization.