The DMC should have the following terms of reference:
1. To monitor the data from the trial and to make recommendations to the TSC (following each DMC meeting) on whether there are any ethical or safety reasons why the trial should not continue.
2. The safety, rights and well-being of the trial participants are paramount.
3. To determine if additional interim analysis of trial data should be undertaken.
4. To consider the data from interim analyses, unblinded if considered appropriate, plus any additional safety issues for the trial and relevant information from other sources.
5. To consider any requests for release of interim trial data and to recommend to the TSC on the advisability of this.
6. The DMC may be asked by the TSC, Trial Sponsor or BHF to consider data emerging from other related studies.
7. If funding is required above the level originally requested, the DMC may be asked by the Chief Investigator, TSC, Trial Sponsor or BHF to provide advice and, where appropriate, information on the data gathered to date in a way that will not compromise the trial.
The membership of the DMC should be completely independent of the trial and will usually be small - three to four members.
The members should be:
- Expert(s) in the field (e.g. clinician with experience in the relevant area)
The DMC should meet at least annually, or more often as appropriate, and meetings should be timed so that reports can be fed into the TSC meetings.
Meetings should be called for and organised by the Chief Investigator of the trial in association with the Chairperson of the DMC. Dates for DMC meetings should be agreed in advance and only altered with agreement of all members. All significant communications between the Chief Investigator and the DMC should be in writing, or if they have to be verbal, they should be backed up by written records.
The role of the DMC is to look at the (unblinded) data from an ethical standpoint, the safety rights and wellbeing of the participants being paramount. The DMC is the only body involved in the trial that has access to the unblinded comparative data.
The Principal Investigators (normally the trial statistician) should prepare a comprehensive report for the DMC. This should be prepared and circulated well in advance of the meeting to allow DMC members time to study the data. The content of the report should be agreed in advance with the DMC Chairperson. The trial statistician may be invited by the Chairperson to attend part of the meeting to present the data; otherwise, no one involved with the trial or TSC should be present to see the unblinded data.
A full confidential report should be made in writing by the Chairperson of the DMC providing advice to the TSC (and Chief Investigator) on whether the trial should continue or not. If the DMC recommends that the trial should be stopped at any point, the BHF should be notified. It is the responsibility of the TSC to decide whether or not to act on the information received from the DMC.
Information provided by the DMC is likely to fall into the following categories:
- Information that might lead to the TSC stopping the trial prematurely in the event of a clear outcome if this is deemed to be appropriate in light of the accumulating data from the study or on the basis of information available from other sources
- Information that might lead to the TSC modifying the design of the trial if this is deemed to be appropriate in the light of the accumulating data from the study or on the basis of information available from other sources.
If at any stage an extension to the grant is needed the DMC may be requested by BHF to provide information on the data gathered to date (from this and other studies) and advise on the likelihood that continuation of the trial will allow detection of an important effect. This should be done using methods that do not unblind the trial.