Decentralized clinical trials in the trial innovation network: Value, strategies, and lessons learned.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or "hybrid" trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

Demonstration Project: Transitioning a Research Network to New Single IRB Platforms.

Since the 2016 National Institutes of Health (NIH) mandate to use a single IRB (sIRB) in multicenter research, institutions have struggled to operationalize the process. In this demonstration project, the University of Utah Trial Innovation Center assisted the Collaborative Pediatric Critical Care Research Network to transition from using individually negotiated reliance agreements and paper-based documentation to a new sIRB master agreement and an informatics platform to capture reliance documentation. Lessons learned that can guide other academic institutions and IRBs as they operationalize sIRBs included the need for sites to understand what type of engagement or reliance is required and their need to understand the difference between reliance and activation. Requirements around local review remain poorly understood. Further research is needed to determine approaches that can achieve the NIH vision of reviews becoming more efficient and improving study start-up times, relieving administrative burden while advancing human research protections.

Securely sharing DSMB reports to speed decision making from multiple, concurrent, independent studies of similar treatments in COVID-19.

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.

Key lessons and strategies for implementing single IRB review in the Trial Innovation Network.

The Trial Innovation Network has established an infrastructure for single IRB review in response to federal policies. The Network's single IRB (sIRBs) have successfully supported over 70 multisite studies via more than 800 reliance arrangements. This has generated several lessons learned that can benefit the national clinical research enterprise, as we work to improve the conduct of clinical trials. These lessons include distinguishing the roles of the single IRB from institutional Human Research Protections programs, establishing a consistent sIRB review model, standardizing collection of local context and supplemental, study-specific information, and educating and empowering lead study teams to support their sites.

MyCap: a flexible and configurable platform for mobilizing the participant voice.

This paper provides a description of the MyCap data collection platform, utilization metrics, and vignettes associated with use from diverse research institutions. MyCap is a participant-facing mobile application for survey data collection and the automated administration of active tasks (activities performed by participants using mobile device sensors under semi-controlled conditions). Launched in 2018, MyCap is a no-code solution for research teams conducting longitudinal studies, integrates tightly with REDCap and is available at no cost to research teams at academic, nonprofit, or government organizations. MyCap has been deployed at multiple research institutions with application usage logged across 135 countries in 2021. Vignettes demonstrate that MyCap empowered research teams to explore and implement novel methods of information collection and use. MyCap's integration with REDCap provides a comprehensive data collection ecosystem and is best suited for longitudinal studies with frequent requests for information from participants.

The IRB Reliance Exchange (IREx): A national web-based platform for operationalizing single IRB review.

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.

"You Really Do Have to Know the Local Context": IRB Administrators and Researchers on the Implications of the NIH Single IRB Mandate for Multisite Genomic Studies.

In 2016, the U.S. National Institutes of Health (NIH) announced a new policy requiring single institutional review board (sIRB) review for multisite studies. However, adherence to the new policy requires the separation of regulatory institutional review board (IRB) work per Federal guidance from site-specific local compliance concerns. In particular, genomic research is subject to a wide range of state laws, institutional requirements, and local population preferences. In this qualitative study, we explored the anticipated needs of genomics researchers and IRB administrators around implementing the policy. We observed multiple uncertainties, particularly about intersite communication processes, sIRB selection processes, and roles of the reviewing IRB and local sites regarding local context information relevant to genomics. Optimal implementation of the NIH policy may require additional guidance for researchers and IRB administrators.