Partner Introduction (Innovative Medicines Canada): 2-min video.

• Summary: Dr. Bettina Hamelin (President, Innovative Medicines Canada) discusses Innovative Medicines Canada, an organization that partners to champion policies that drive the discovery, development and delivery of transformative medicines and vaccines to all Canadians to live longer and healthier lives.

NIH Pragmatic Trials Collaboratory (Grand Rounds) - Data and Safety Monitoring in Pragmatic Clinical Trials (December 8, 2017): 39-min presentation & 20-min Q&A (38-slide presentation)

• Summary: Drs. Jeremy Sugarman, Susan Ellenberg, and Greg Simon discuss the need for data and safety monitoring boards (“DSMBs” - also referred to as data monitoring committees [“DMCs”]) and the special considerations related to these boards/committees in pragmatic trials. Specific topics that are discussed include: (1) Do pragmatic trials need DSMBs? (2) What gets monitored? (3) Participant follow-up, (4) Data analysis, and (5) DSMB composition.

Simon GE, et al. Principles and procedures for data and safety monitoring in pragmatic clinical trials. Trials. 2019 Dec 9;20(1):690. (8-page paper)

• Summary: While all trialists have ethical and regulatory obligations to monitor participant safety and the integrity of the trial, the processes through which one meets these obligations may differ between pragmatic trials and traditional explanatory trials. Just as the design, implementation, and management of pragmatic trials typically involves necessary departures from the approaches taken in explanatory trials, the appropriate data and safety monitoring of pragmatic trials typically requires departures from the practices deployed in explanatory trials. Therefore, it is argued that pragmatic trialists should not adopt, by default, the monitoring procedures used in explanatory trials. Instead, trialists should consider the core principles of trial monitoring, and, subsequently, design procedures appropriate for their specific trial.

NIH Pragmatic Trials Collaboratory (Living Textbook): Section 2 - Which Pragmatic Trials Should Have a DSMB? (Chapter: Ethics & Regulatory - Data and Safety Monitoring): 1-page website.

• Summary: There are several factors to consider when determining if a DSMB is the preferred approach to data and safety monitoring. This page provides a list of criteria (pulled from modified FDA guidance, content current as of: December 3, 2021) for when to consider a DSMB: (1) Is the trial a large, multicenter study of long duration? (2) Is the study endpoint such that a finding in the interim analysis might ethically require termination of the study before its planned completion? (3) Are there a priori reasons for a particular safety concern (for example, a particularly invasive treatment?) (4) Is there prior information suggesting the potential for serious toxicity due to the study treatment? (5) Is the study being performed in potentially scientifically complex or vulnerable populations (such as children, pregnant women, elderly patients, terminally ill patients, those with diminished capacity)? (6) Is the study being performed in a population at elevated risk of death or other serious outcomes, even when the study objective addresses a less serious endpoint? A brief description of the data monitoring plans for several NIH Collaboratory trials is also listed in a table.

NIH Pragmatic Trials Collaboratory - Data Monitoring in Pragmatic Clinical Trials: Points to Consider (June 28, 2021): 3-page document.

• Summary: There are several approaches one may consider in a pragmatic trial: (a) An independent data and safety monitoring board/committee; (b) Designation of a single independent monitor; or - if appropriate - (c) A documented plan for when and how a designated research team member will monitor study conduct and results. Selection of an approach will depend on the characteristics of the trial, including the level of research risk, the vulnerability of the study population, and the size/complexity of the trial. Points to consider when making this decision are: (1) Composition of the monitoring committee/board, (2) Use of health systems records data, (3) Study design and statistical analysis, (4) Monitoring of intervention adherence, (5) Futility determinations (and early termination), (6) Safety, (7) Efficacy, and (8) Describing the experiences of the monitoring committee/board.

Irving E, et al. Series: Pragmatic trials and real world evidence: Paper 7. Safety, quality and monitoring. J Clin Epidemiol. 2017 Nov;91:6-12. (7-page paper)

• Summary: Describes the practical challenges of collecting and reporting safety data and of monitoring trial conduct in the context of trials embedded in routine care. It is noted that the balance of risks (and potential impact) in a pragmatic trial will be different from a traditional (explanatory) trial. The approach taken for data and safety monitoring in a pragmatic trial is likely to differ compared to an explanatory trial. Therefore, this will require early and detailed discussions with research ethics boards and regulatory authorities (if applicable).

NIH Pragmatic Trials Collaboratory - Template: Data Monitoring Committee (DMC) Charter for Pragmatic Clinical Trials (August 22, 2017): 7-page template.

• Summary: A customizable template for a Charter for DSMBs/DMCs for pragmatic trials. The Charter defines the primary responsibilities of the board/committee, its relationship with other aspects of the trial, the board/committee membership, and the purpose/timing of its meetings. The Charter also provides guidance ensuring confidentiality of emerging data and deliberations of the board/committee, for minimizing conflicts of interest, and for statistical monitoring guidelines to be considered by the board/committee (if any). The template also addresses the content of the reports that may be provided to the board/committee.

Ellenberg SS, et al. Data monitoring committees for pragmatic clinical trials. Clin Trials. 2015 Oct;12(5):530-6. (12-page paper)

• Summary: A data and safety monitoring plan must be described in the trial protocol and approved by the research ethics board, and there are several approaches one may consider in a pragmatic trial. However, pragmatic features of a trial may pose challenges in terms of deciding which aspects of a trial to monitor and when it is appropriate for, say, a DSMB/DMC to intervene. Using the PRECIS tool, characteristics of pragmatic clinical trials that may have implications for monitoring boards/committees are reviewed.

Curtis LH, et al. Monitoring in pragmatic trials lessons from the NIH pragmatic trials collaboratory. Contemp Clin Trials. 2025 May;152:107866. (6-page paper) * As this is an optional resource, an institutional login (e.g., university or research institute e-mail address) is required to access this material.

• Summary: The NIH Pragmatic Trials Collaboratory, which supports the conduct of several pragmatic trials, illustrates the distinguishing characteristics of pragmatic trials which require special attention when developing a data and safety monitoring plan. Characteristics that may require additional considerations relate to: (1) Pragmatic clinical trials are large in scope, (2) Participants are often identified using routinely collected health data sources, (3) Trialists typically have less control over interventions, (4) Outcome data are often extracted from routinely collected data, and (5) Study activities are intertwined with usual care.