Guidelines for Data and Safety Monitoring in Pragmatic Randomized Clinical Trials Using Case Studies

Abstract

Pragmatic randomized clinical trials (pRCTs) have a unique set of considerations for data and safety monitoring. Because of their unconventional trial designs coupled with collection of multilevel data and implementation outcomes in real-world settings, thoughtful consideration is needed on the presentation of the trial design and accruing data to facilitate review and decision-making by the trial's data and safety monitoring board (DSMB). To our knowledge, there is limited information available in practical guidelines for generalists and medical general practitioners on what to monitor and to report to the DSMB during the conduct of pRCTs and what the DSMB should focus on in its review of reports. This article discusses these matters in the context of 3 case studies focusing on a set of critical data and safety monitoring questions that would be of interest to the generalist conducting pRCTs. In considering these questions, we provide tabular and graphical illustrations of how data can be presented to the DSMB while drawing attention to those areas that the DSMB should focus on in its review of the trial. The strategies and viewpoints discussed herein provide practical guidelines and can serve as a resource for the generalist conducting pRCTs.

Trial registration: ClinicalTrials.gov NCT03766009 NCT03857620 NCT04000087.