Data Monitoring Committee (DMC): (also known as Data Safety Monitoring Boards (DSMBs) and Data Monitoring and Ethics Committee (DMEC))
Data Monitoring Committees (DMCs) also known as Data Safety Monitoring Boards (DSMBs) and Data Monitoring and Ethics Committee (DMEC) play a vital role in the safety of clinical trials and also enhance the validity and integrity of the results collected from trials. While trial Investigators and Sponsors run the day-to-day management of clinical trials, DMCs make suggestions concerning the overall conduct of the trial.
According to the International Conference on Harmonisation’s (ICH) guidelines on Good Clinical Practice (GCP) and Statistical Principles for Clinical Trials, Data Monitoring Committees (DMCs) are “an independent data monitoring committee that may be established by the sponsor to access at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, or modify or stop a trial.”
Data Monitoring Committees (DMCs) are selected by trial Sponsors and are put in place to protect the interests of clinical trial participants and to provide integrity and credibility to the trials themselves. They have an advisory role and should be entirely independent from trial Sponsors and Investigators. DMCs should be the only individuals performing the interim analysis with access to data on the efficacy and safety of the investigational product and the clinical trials.
Their independence from trial Sponsors and Investigators and the confidentiality of the interim data ensures that unreliable results won’t be spread around and taken as fact. It also reduces any prejudgements that can have a detrimental effect on enrolment and the flexibility to implement any modifications to the trial. DMCs can be objective in their recommendations and the trial Sponsors can make decisions without any bias or prior knowledge of the interim study results. Whether the DMCs advice is accepted, is entirely up to the trial Sponsors.
Types of DMCs:
- Where members are fully independent from the investigational product, the trial Sponsor/Investigator and the clinical trial site. Mostly used in commercial clinical trials.
- Where members may be affiliated with the same institution as the trial Sponsor/Investigator but aren’t an official part of the trial team. Mostly used in non-commercial trials.
DMCs are usually utilised in:
- Later phase clinical trials which address major health outcomes
- High-profile clinical trials
- Clinical trials which are seeking regulatory approval
- Clinical trials where there is a high risk of harm or unknown risks
- Double-blind clinical trials
- Clinical trials which lack standard operating procedures (SOPs)
DMC’s should be selected based on the following criteria:
- Relevant experience with clinical trials
- Experience with serving on other Data Monitoring Committees (DMC)
- No past financial or intellectual conflicts of interest (having strong opinions about the investigational product)
Recruiting a DMC:
The members of a DMC should include clinicians and at least one biostatistician with prior experience in dealing with clinical trial conduct, methodology and interim data analysis. DMCs are typically made up of at least 3 members, although larger groups can exist for bigger studies.
Members of a DMC should be recruited under ‘independent scientist agreements’ which removes the risk of any conflicts of interest and emphasises that the DMC are independent from the trial Sponsor who use their scientific expertise to interpret the trial data without any bias.
A DMC contract should cover:
- The purpose and areas of responsibility of the DMC for the particular trial.
- The terms of confidentiality: DMCs are granted access to interim data but are obligated to keep the data confidential. Any leaks can jeopardize the integrity of the trial.
- That the scientific insights collected from the trial are the intellectual property of the Sponsor. However, any methods for the design or analysis of trials that have been newly developed by the DMC are the intellectual property of the DMC.
- The terms of compensation provided by the Sponsor. Typically, DMCs aren’t covered for liability as they are not employees of the Sponsor. However, DMCs are increasingly being indemnified by the trial Sponsors, although this only occurs after a DMC has requested indemnification and after a lengthy negotiation process.
- The amount of money paid to each individual DMC member per hour or per meeting. The amount of money paid is determined by the level of expertise of each member and the roles that they’re required to perform.
A DMC Charter is a document which defines the responsibilities of the DMC, their relationship with other trial components and the agenda for each meeting they hold. They also set the guidelines for statistical monitoring, ensuring confidentiality and communication, and an outline for the Open and Closed Reports that will be provided to the DMC.
The guidelines set by the Charter should be discussed and approved by both the DMC and the trial Sponsors at the DMC Organisational Meeting which is held before the clinical trial takes place.