NIGMS Guidelines for Data and Safety Monitoring in Clinical Trials

Introduction

A clinical trial is defined by NIH as a research study in which one or more human subjects are prospectively assigned to one or more interventions to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. Clinical trials must be submitted to NIH through clinical trial-specific funding opportunity announcements. As part of the application process, NIH requires a data and safety monitoring plan that is commensurate with the risks of the trial, its size and complexity. The minimal elements of a data and safety monitoring plan are described in Section 3.3 of G.500 – PHS Human Subjects and Clinical Trials Information and include:

  • The overall framework for safety monitoring and what information will be monitored.
  • The frequency of monitoring, including any plans for interim analysis and stopping rules (if applicable).
  • The process by which Adverse Events (AEs) Link to external web site, including Serious Adverse Events (SAEs) Link to external web site such as deaths, hospitalizations, and life threatening events and Unanticipated Problems (UPs), will be managed and reported, as required, to the IRB, the person or group responsible for monitoring, the awarding IC, the NIH Office of Biotechnology Activities, and the Food and Drug Administration Link to external web site.
  • The individual(s) or group that will be responsible for trial monitoring and advising the appointing entity.

In addition to the elements listed above, NIGMS recommends that all clinical trial data and safety monitoring plans address:

  • The frequency of reporting progress/enrollment to NIGMS.
  • Risk assessment and expected safety issues.
  • Procedures for ensuring protocol compliance/reporting protocol violations.
  • Methods for determining data accuracy/quality assurance monitoring.
  • Plans for data storage, access and security.

Approaches to Data and Safety Monitoring

Independent Medical Monitor

An independent medical monitor is a physician with relevant expertise whose primary responsibility is to review individual and cumulative adverse events and make recommendations regarding the safe continuation of the study. Use of an independent medical monitor may be sufficient oversight for small trials that are considered to be of low risk to participants. An independent medical monitor may also be used in larger trials in conjunction with a safety monitoring committee and/or a data and safety monitoring board.

Safety Monitoring Committee

A safety monitoring committee is an independent group of experts whose primary responsibility is to make recommendations based on issues that present immediate safety concerns. Safety monitoring committees may review adverse event data on a regular basis but typically do not perform interim evaluations of efficacy. Safety monitoring committees may be appointed at the initiation of a trial or convened as needed on an ad hoc basis.

Data and Safety Monitoring Board

Data and safety monitoring boards have broad oversight responsibilities that include but are not limited to:

  • Trial performance (recruitment/retention, protocol adherence, data quality/completeness).
  • Patient safety.
  • Efficacy of the intervention (i.e., interim analyses).
  • Review of ancillary studies and protocol modifications.

All Phase III, multi-site clinical trials funded by NIGMS require oversight by an independent data and safety monitoring board. A data and safety monitoring board may also be used for oversight of Phase I or Phase II trials that:

  • Have multiple sites of patient enrollment.
  • Test high-risk interventions.
  • Have more than 100 participants.
  • Involve special populations (e.g., persons with impaired ability to consent).

Conflicts of Interest

NIGMS expects medical monitors, safety committees and data and safety monitoring boards to be viewed as independent. Thus, the individuals who perform these roles must be free of financial and academic conflicts that may indicate bias towards a particular outcome. Examples of potential conflicts include but are not limited to: financial arrangements that reward a particular study outcome, proprietary interest in the intervention being tested, significant equity in the manufacturer of the intervention or recent collaborations/employment with the trial principal investigator. It is the responsibility of the individual monitor/member to promptly disclose any real or apparent conflicts to the NIGMS clinical trial liaison.

References

Inquiries

NIGMS welcomes questions and comments from potential applicants. Inquiries may be directed to:

Sarah E. Dunsmore, Ph.D.
National Institute of General Medical Sciences
National Institutes of Health
45 Center Drive MSC 6200
Bethesda, MD 20892-6200

Guidelines last updated April 25, 2019