July 28, 2017: The DSMB Role in Pragmatic Trials: NIMH Progress and Challenges


Galia Siegel, PhD, National Institute of Mental Health (NIMH)

Anna Ordonez, MD, MAS, National Institute of Mental Health (NIMH)

Scott Kim, MD, PhD, Department of Bioethics Clinical Center, National Institutes of Health

Kate Comtois, PhD, MPH, Harborview Medical Center, University of Washington School of Medicine


The DSMB Role in Pragmatic Trials: NIMH Progress and Challenges


Data and Safety Monitoring Boards; DSMB; Pragmatic clinical trial; Clinical trial registries; CTTI; Post-randomization informed consent; Study designs; Zelen design; Stepped-wedge randomization; Suicide Prevention Outreach Trial (SPOT)

Key Points

  • Pragmatic trial study designs that involve post-randomization informed consent or stepped-wedge randomization pose new challenges for review by Data and Safety Monitoring Boards (DSMBs).
  • The FDA will now allow a waiver or alteration of informed consent for qualifying randomized controlled pragmatic trials.
  • Experiences in the NIMH-funded Suicide Prevention Outreach Trial (SPOT) suggest a need for better knowledge of the implications of post-randomization consent design in clinical trials.
  • Potential benefits of post-randomization consent for research participants include reduced burden and less unnecessary information on the consent form. This type of informed consent also better mimics real-life outcomes. Benefits of post-randomization consent for investigators include 100% participation in the trial’s control arm and fewer resources needed for the consent process.

Discussion Themes

When there is an opportunity to obtain consent, when is waiver permissible?

Include stakeholders in discussions of thresholds for study participation and plans for safety monitoring.

A high refusal rate in post-randomization consent may lead to selection bias, which is a threat to the benefit of randomization.

There is a delicate balance between the interests of the participant and the interests of the trial, making the monitoring of adverse events so critical.

For More Information

To learn more about data monitoring in pragmatic trials, visit http://ctj.sagepub.com/content/12/5/530.full

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