The Data Safety and Monitoring Board (DSMB) or Data Monitoring Committee (DMC – these are synonymous terms) is a group of individuals put together by the sponsor or CRO (if contracted out) with relevant expertise to carry out the important role of monitoring the safety of a clinical trial study.
Click here to view further information on DSMBs as part of the Global Health Research Process Map - a step-by-step guide to planning successful global health research projects. You will find information such as when a DSMB is needed, how to set one up and their roles and responsibilities. There's also a variety of other resources including a downloadable template DSMB charter, links to a free e-learning course and lots of other useful resources on DSMBs.
The DSMB needs to be independent and external to the sponsor and will review the accumulating safety data from an ongoing clinical trial on a regular basis. The data will remain blinded unless there is a reason why the blind must be broken. In this case it is typically only broken to the DSMB; the rest of the study team remain blinded.
While safety monitoring should be the major task for a DSMB, other aspects of a clinical trial (e.g. study integrity, design aspects) might also be considered or assessed by the board. A DMC has to be fully functional prior to study enrolment to enable them respond to any safety signal.
Requisite for a DSMB
All clinical trials need some form of safety oversight and safety monitoring but not all clinical trials require a DSMB. Typically, DSMBs are convened for large randomised multi-centre studies where the aim is to prolong life or reduce the risk of an adverse event. There is no hard and fast rule about when to set up a DSMB, but one primary reason is when any risk is presented by the study intervention – or indeed when the intervention could provide significant benefit to patients. In both cases the trial should be stopped as soon as either clear benefit is shown by statistically significant analysis of the data, or that the intervention is doing harm. Interim analysis could show that these answers have been arrived at earlier than the end of the trial and in this case the study should be stopped early.
Other reasons for a DSMB include:
- Studies where an interim analysis has already been planned in the protocol. The sponsor may want to assess the safety at that point as well as efficacy.
- For complex study designs where the end point, whether favourable or unfavourable, could lead to a modification in the study design.
- In studies performed in vulnerable patients such as children, pregnant women, elderly patients or those who are terminally ill or have diminished responsibility.
Constitution and Responsibilities of a DSMB
The membership of the DSMB should reflect the disciplines and medical specialities necessary to interpret the data from the clinical trial and to fully evaluate participant safety. The number of DSMB members depends on the phase of the trial, range of medical issues, complexity in design and analysis, and potential level of risk but generally consists of three to ten members including, at a minimum:
- Expert(s) in the clinical aspects of the disease/patient population being studied
- One or more biostatisticians; and,
- Investigators with expertise in current clinical trials conduct and methodology.
Where necessary, it may be required to invite experts in specialist fields such as pharmacokinetics, toxicology or bioethicist who can provide expert knowledge in specific areas. Invited members are usually ad hoc members of the board and may not be required to vote at meetings. Potential DSMB members should not just have scientific expertise, but should also have experience of study design and ideally should have sat on previous DSMB meetings. Members of the DSMB should have no conflict of interest and no financial interest in the study or the company/research group, or authorship of any resulting research papers. The DSMB should review each protocol for any major concern prior to implementation. As part of its task, the DSMB should also consider essential protocol adherence, number of protocol violations and early patient withdrawal as these might be indicators to the safety of the study drug or device.
The DSMB will review the data provided to them by the sponsor for its timeliness, completeness, and accuracy and that they are sufficient for evaluation of the safety and welfare of study participants.
Roles of the DSMB:
- Monitoring the safety of subjects as pre-specified in the DSMB plan by accessing data to perform a risk/benefit assessment in order to weigh possible disadvantages against a possible gain in efficacy. Though the main part of the DSMB’s role can be performed with blinded data, it is important that the DSMB is allowed access to unblinded data if necessary for safety – but without unblinding the study team.
- Review the efficacy of the treatments being tested and independently make recommendations to researchers e.g., terminate a clinical trial because the analyses indicate the study is having a negative effect, the intervention is not adequately implemented or there is no evidence of a treatment effect after the prescribed level of power is reached.
- Check for the presence of early unanticipated therapeutic results, side effects or adverse consequences and independently make recommendations to the sponsor e.g., terminate a clinical trial because it would be unethical to continue the non-treatment/ treatment as usual arm.
- Review the performance of the trial e.g., protocol violations, improper entry criteria, slow accrual rate, low participation rate, inadequate treatment adherence, inadequate follow-up rate, and to independently make recommendations for improvement or termination if the trial would be unable to prove anything meaningful, regardless of modifications. Early withdrawals or protocol adherence may indicate of possible problems with efficacy or safety.
They will make recommendations on further study conduct. Such recommendations include continuing, terminating or modifying the trial. The implementation of any DSMB’s recommendation is solely the responsibility of the sponsor who can decide on what action to take. Confidentiality must always be maintained during the DSMB reviews and deliberations, and therefore, the structure of the DSMB meetings is such that they consist of an “open” and “closed” sessions, and an executive session. The open sessions provide the sponsor and other stakeholders the chance to update the DSMB with the progress of the trial to date and provide clarification on the data provided etc. The “closed” meeting is an opportunity for the DSMB to meet without the sponsor (or their representative) to deliberate on the outputs of the study data submitted and to make recommendations. Where necessary, the biostatistician or ad hoc members may attend this session to provide relevant expertise. Only the DSMB may attend the executive session in which they confidentially review the data provided and conduct voting procedures.
As soon as possible, the DSMB charter should be drawn up. The charter is the Standard Operating Procedure for the DSMB and can be written by the sponsor and approved by the DSMB, or can be written by the DSMB. The charter describes the roles and remit of the DSMB throughout their participation in the study. It also includes the timings and frequency of the meetings, the types of meetings i.e. telephone/video conferences, face-to-face meetings or both.
- The timings of the meeting are usually driven by recruitment figures or by trial events.
- The charter will also describe how the DSMB will communicate to the sponsor or its representatives and vice versa.
Ultimately, it is the sponsor’s responsibility to progress with all or some of the DSMB’s recommendations, as this responsibility cannot be transferred to the DSMB.
You can download a template DSMB charter from the resources section see the article 'Trial Oversight Committee'.
Alternatives to a DSMB
In studies where a DSMB is not needed, which is typically when the interventions are known to be very safe or the trial is very short, then other forms of safety monitoring are appropriate and recommended.
Appointing a local safety monitor is a good alternative and often put in place in addition to a DSMB. The Local Safety Monitor is a clinician experienced in the field of study. They are independent from the trial and their role is to review any adverse events and give an independent review of the causal relationship to the trial intervention.
To take an eLearning course about DSMBs, click here.