The concept of DMCs was initially introduced in 1967 by the Greenberg Report to provide oversight to randomized clinical trials sponsored by the National Heart Institute. Among its recommendations is that trials should not be modified or terminated without the input from an independent group of scientists otherwise not involved in the conduct of the trial. Trials might be terminated because the intervention’s benefit was clearly established, there was sufficient evidence of harm, the trial was no longer viable or of interest, or some other compelling reason.

The application of these recommendations in early NIH-sponsored cardiovascular trials led to the establishment of the independent data and safety monitoring board (DSMB) or more simply the Data Monitoring Committee (DMC). The charge to the DMC was to monitor trial conduct and safety and recommend trial changes or closure. Today, DMCs are used across therapeutic areas and may oversee single trials, groups of related trials, or the entire portfolio of research related to an investigational product. Membership of the independent DMCs may be internal to the trial sponsor, completely external, or a mix, depending on the nature of the trial. Responsibilities may be limited to analyses of efficacy and safety, or expanded to include review of data quality and other trial operations. As use of DMCs has increased and evolved, critical issues have emerged, including the following:

• Differences in DMC roles and responsibilities that contribute to confusion and unclear expectations between DMCs and other trial stakeholders, including sponsors, contract research organizations, regulators, the scientific community, and patients
• Ineffective, inappropriate, and/or confusing methods of communication between DMCs and other trial stakeholders before, during, and after trial conduct
• Mismatch between needs and availability of DMC members, and lack of a clear plan for preparing the next generation of DMC members

Data Monitoring Committees (DMCs) (2014-2016)

• Describe the current landscape of DMC use and conduct
• Clarify the purpose of and rationale for using a DMC
• Identify best practices for independent DMC conduct, including:
  • Statistical support
  • Member qualification
  • Member make-up
• Describe effective communication practices between independent DMCs and trial stakeholders during all phases of DMC activity, including:
  • Charter preparation and maintenance
  • Provision of statistical reports to the DMC
  • How and to whom the DMC reports findings under various circumstances
  • How information generated by the DMC is reported to regulatory bodies
• Identify strategies for preparing the next generation of DMC members

DMCs composed of qualified members are convened for appropriate trials and conduct business in a way that is understood by all stakeholders and increases the quality of trial oversight.

• The project conducted a survey to:
  • Assess current use and conduct of DMCs
  • Assess training practices for DMC members
• The project convened focus groups to gain an in-depth understanding of needs and best practices related to independent DMC use.
  • Focus groups were organized by area of expertise: DMC members, patient/patient advocate DMC members, pharmaceutical and device clinical trial sponsors, government and non-profit clinical trial sponsors, IRB and FDA representatives, and statistical analysis center representatives.
• The project held an expert meeting to bring together various stakeholders to discuss findings from the survey and focus groups, and consider possible project recommendations.

Results indicate that stakeholders from academia, industry, and government view the most important activity for DMCs to perform is to review both summary adverse events (AEs) and primary outcomes by treatment arm to assess the risk-benefit profile of an investigational product. According to responses, Phase 3 trials are more often reviewed by DMCs than other phases.

Focus groups were assembled to understand different perspectives on DMC use. The focus group, composed of DMC members, felt that DMC roles should be dictated by a well-defined charter, they should have a limited role in the trial design to avoid potential investment/biases, and they should be provided unmasked treatment assignment data and have access to efficacy data. The focus group with FDA and IRB members indicated that the primary role of DMCs should be to conduct a detailed analysis of safety; however, this group felt that DMCs were overused. The industry sponsor focus group responded that DMCs are mainly employed in multicenter trials and RCTs that require DMCs; however, company policies vary.

Survey and focus group findings indicate that many sponsors have SOPs governing the conduct of DMCs and a DMC charter template that is tailored to each specific trial. Experts discussed the use of charters to communicate more clearly with DMCs. Specifically, that the charter should be the appropriate length, address DMC independence, pre-specify the planned contents of the DMC report, be clear but flexible about how decisions are to be made by the DMC, address trial blinding, and detail communication practice between all parties, including the frequency and format of meetings. While both the DMC and sponsor may benefit from close communication during charter development, interactions can be minimized once the charter is finalized so that DMCs can operate independently.

Experts also discussed the composition of DMCs, exploring the need for members to have different areas of expertise including ethics, statistics, and clinical or research experience in a particular therapeutic area. DMC members are identified via multiple different avenues. Qualifications for DMC membership should be more well-defined, and the DMC chair should be especially well-versed in clinical trials and have adequate previous experience with DMCs. Plans for future DMC members may include prospective training to better prepare them for DMC activities. The core curriculum should include didactic and interactive training sessions as well as an apprenticeship.

Presentations that describe findings are available here.

Organization affiliations are listed as active affiliations during the project.

*Indicates former project manager, team leader, or team member.