A decision about who will conduct data and safety monitoring is made during the protocol design stage by the investigator and study sponsor and is then reviewed by the IRB. In instances where it is impossible for any one investigator to conduct data and safety monitoring for an entire study, and study sponsors are likely to have conflicts of interest, a DSMC is often formed. For example, DSMCs are widely used in Phase III clinical trials where multiple investigators are involved and may be working at centers across the country or around the world. Other factors influencing the decision to establish a DSMC are discussed elsewhere in this module.
A DSMC is made up of an independent team of specialists, each having a particular area of expertise. Experts are selected for their knowledge of the issues under study (e.g., the disease, drug, device, scientific topic, or procedure) or the methodologies employed (clinical trials, data management, statistical analysis). In some cases team members may include individuals with specialized expertise, such as in research ethics or biomedical ethics. Membership of DSMCs formed by Yale investigators should contain at least three internal or external research scientists and potentially more, depending on the nature of the study (e.g., level of risk). In some instances, such as when the institution or an investigator has a conflict of interest, additional neutral or unaffiliated members are included. It is imperative that the members of the committee be neutral and objective (e.g., have no financial or other disqualifying conflict of interest) and that the data presented to them by the sponsors or investigators be accurate.
The DSMC always monitors risk data (reports of adverse events) to assess the safety of participants, often monitors efficacy data to assess the likelihood that the study will lead to generalizable knowledge, and occasionally monitors data acquisition to assess the integrity of the data. DSMCs are generally funded by the study sponsor and meet at predetermined intervals, typically several times per year. The collected data are evaluated to determine if the study, from a scientific and ethical viewpoint, should proceed, be altered or be terminated. Recommendations made by the DSMC are submitted to the study steering committee, sponsor, and/or the investigator for review and potential implementation. DSMCs rarely have decisional authority. DSMCs may recommend that a study be terminated if the risks to subjects are too high or if, with an appropriate degree of certainty, a conclusion regarding the hypothesis has been reached. By terminating a study early, a DSMC protects subjects by minimizing their exposure to more risky or less effective therapies. DSMCs must regularly report (as outlined the study’s monitoring plan) their findings and recommendations to the study steering committee or sponsor. Summary reports are generally prepared for the investigator(s) at each institution participating in the study. Investigators must always make certain that the IRB receives a copy of the summary reports they receive.
The National Cancer Institute has published a policy statement on data and safety monitoring of clinical trials that describes when committees should be established, their responsibilities, guidelines on committee membership and disclosure of conflicts of interest, and guidelines on the reporting of recommendations and release of data. Other governmental agencies also publish guidance documents on their websites that describe their expectations for data and safety monitoring of clinical trials.