Data & Safety Monitoring

Institutes and Centers (ICs) must provide a system for appropriate oversight and monitoring of clinical trials to ensure the safety of research subjects and the validity and integrity of the data.

Depending on the level of risk, an independent Data and Safety Monitoring entity may be required to ensure safe and effective study conduct. This entity may recommend ending the trial when significant benefits or risks are identified, or when the trial is unlikely to achieve its primary goals.

• A DSMP identifies and documents monitoring activities needed to protect the safety and welfare of subjects, the validity of the data, and the integrity of the research study. The DSMP should match the level of risk, nature, complexity of the research, and the population under study.
• Monitoring can be done in various ways by different individuals or groups, depending on the size and scope of the research. It ranges from monitoring by the Principal Investigator (PI) or NIH program staff in a small Phase I study to an independent Data and Safety Monitoring Board (DSMB) for a large Phase III clinical trial.
• ICs must provide a system for appropriate oversight and monitoring of clinical trials to ensure the safety of research subjects and the validity and integrity of the data.
• All non-exempt human subjects research protocols in the NIH Intramural Research Program must include a DSMP.
• The DSMP must be described in the written protocol and should be tailored to the specific protocol.

• Procedures for communication between relevant groups such as the PI and research team members, the study sponsor, the data and safety monitoring entity, the IRB, the coordinating center, the FDA, and other study sites.
• Individual stopping rules and/or study stopping rules.
• Plans for interim and/or futility analyses.
• The frequency of any assessments or reviews of data and events.
• The identity and description of an independent Data and Safety Monitoring Entity.

A Data and Safety Monitoring Entity is an individual or group assigned to conduct interim monitoring of data from research activities. The NIH IC, FDA, Sponsor, or IRB can require that a DSMP identify a data and safety monitoring entity that is independent from the PI, chosen based on the research's risk level.

Examples of Data and Safety Monitoring Entities at NIH

• Principal Investigator (PI): At minimum, the PI must perform monitoring as part of their oversight duties. If the PI is not a medical staff member and the protocol requires direct medical care or clinical consultation, a Medical Advisory Investigator (MAI) must also be identified.
• Independent Safety Monitor (ISM): An ISM is an independent physician or expert with relevant expertise, responsible for providing independent monitoring of clinical trials. The ISM must be free from any professional or financial conflict of interest (COI) with the research project or study investigators. ISMs are typically used for small early-phase trials considered lower risk but can also be used in higher-risk studies along with a DSMB. ISMs are also used in studies where the PI is blinded to the treatment arm.
• Safety Monitoring Committee (SMC): An SMC functions similarly to a DSMB but is convened by the NIH IC. Depending on the Institute, they may focus on reviewing events related to safety concerns and may not perform interim analyses or evaluations of clinical endpoint data. Refer to the specific IC requirements for details.
• Data and Safety Monitoring Board (DSMB): A DSMB is a formal committee of independent experts that reviews accumulating data and critical efficacy endpoints from ongoing clinical trials, including multi-site research. It conducts interval assessments of clinical trial progress, safety data, and critical efficacy variables and recommends to the sponsor whether to continue, modify, or terminate a trial. The DSMB should include clinical trial scientists, medical clinicians knowledgeable in relevant disciplines, and a biostatistician. DSMB members must be independent from any professional or financial conflict of interest with the research project or study investigators. A DSMB may be appropriate for high-risk interventional studies, multi-center clinical trials, blinded studies, or high-risk studies involving certain vulnerable populations. For NIH policy purposes, the terms DSMB, Independent Data and Safety Monitoring Committee (DSMC), and Data Monitoring Committee (DMC) are considered synonymous.