Principles and procedures for data and safety monitoring in pragmatic clinical trials

Gregory E Simon,Robert B Penfold,Patrick O’Connor,Jo Ann M Sperl-Hillen,Susan M Shortreed,Rebecca C Rossom

doi:10.1186/s13063-019-3869-3

Abstract

BackgroundAll clinical trial investigators have ethical and regulatory obligations to monitor participant safety and trial integrity. Specific procedures for meeting these obligations, however, may differ substantially between pragmatic trials and traditional explanatory clinical trials.Methods/ResultsAppropriate monitoring of clinical trials typically includes assessing rate of recruitment or enrollment; monitoring safe and effective delivery of study treatments; assuring that study staff act to minimize risks; monitoring quality and timeliness of study data; and considering interim analyses for early detection of benefit, harm, or futility. Each of these responsibilities applies to pragmatic clinical trials. Just as design of pragmatic trials typically involves specific and necessary departures from methods of explanatory clinical trials, appropriate monitoring of pragmatic trials typically requires specific departures from monitoring procedures used in explanatory clinical trials. We discuss how specific aspects of pragmatic trial design and operations influence selection of monitoring procedures and illustrate those choices using examples from three ongoing pragmatic trials conducted by the Mental Health Research Network.ConclusionsPragmatic trial investigators should not routinely adopt monitoring procedures used in explanatory clinical trials. Instead, investigators should consider core principles of trial monitoring and design monitoring procedures appropriate for each pragmatic trial.

Highlights

All clinical trial investigators have ethical and regulatory obligations to monitor participant safety and trial integrity
Pragmatic trial investigators should not routinely adopt monitoring procedures used in explanatory clinical trials
Depending on the size of the trial, the potential risks of the treatments or interventions under study, and the need for blinded analyses of interim results, responsibility for monitoring might belong to the principal investigator, an independent safety monitor, or an independent Data and Safety Monitoring Board (DSMB)

Summary

Introduction

All clinical trial investigators have ethical and regulatory obligations to monitor participant safety and trial integrity. Regardless of these design differences investigators leading both explanatory and pragmatic clinical trials have the same fundamental ethical obligations to monitor the safety of trial participants, the risks of study treatments, the integrity of trial data, and the likelihood that continuing a trial may not yield a definitive result. Depending on the size of the trial, the potential risks of the treatments or interventions under study, and the need for blinded analyses of interim results, responsibility for monitoring might belong to the principal investigator, an independent safety monitor, or an independent Data and Safety Monitoring Board (DSMB).

Results

Conclusion