A clinical trial is defined by NIH as a prospective, biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices or new ways of using known drugs, treatments or devices). All NIH clinical trials require monitoring that is appropriate to the level of risk to the participants.
For each proposed clinical trial, NIH requires a data and safety monitoring plan as part of the research application. This plan describes oversight and monitoring to ensure the safety of participants. Monitoring may be conducted in various ways or by various individuals or groups, depending on the size and scope of the research effort.
The following sections provide guidance for oversight of NIGMS-funded clinical trials. This guidance does not supersede or replace any of the following:
- Existing policies of the U.S. Department of Health and Human Services on protection of human subjects as described in 45 CFR part 46.
- NIH policies and guidelines for conduct of clinical research, inclusion of women and minorities, research project administration, reporting and financial management.
- FDA regulations relating to good clinical practice and clinical trials that involve investigational new drug applications or investigational device exemptions.
- Requirements of local institutional review boards (IRBs).
Applicants and grantees should be aware of the following NIH policies:
Essential Elements of Data and Safety Monitoring
Data and safety monitoring plans for NIGMS clinical trial applications must include the following elements:
- Who is responsible for monitoring the progress of the trial.
- The frequency of monitoring trial progress and reporting progress/enrollment to NIGMS.
- Risk assessment and expected safety issues.
- Approach to safety monitoring.
- Mechanism for reporting adverse events to the principal investigator, regulatory authorities (IRB, FDA, Office for Human Research Protections, etc.), oversight systems (monitors, committees or data safety and monitoring boards) and NIGMS. Trials with multiple sites of patient enrollment should include a flow chart.
- 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.
NIGMS welcomes questions and comments from potential applicants. Inquiries are encouraged and may be directed to the NIGMS program staff member with whom the applicant/grantee has been in contact.
For questions regarding policy issues, please contact:
Sarah E. Dunsmore, Ph.D.
National Institute of General Medical Sciences
45 Center Drive, Room 2AS.49C
Bethesda, MD 20892
Guidelines last updated March 12, 2012