Data Monitoring Committee guidelines

A Data Monitoring Committee (DMC) should be established for most clinical studies with an element of primary research

The Sponsor should complete a risk assessment to determine the need for a DMC for a clinical study. The BHF will require a formal justification if there is no intention to set up a DMC for a clinical trial and may insist on the set up of a DMC as a condition of funding.

The role of the DMC is to monitor the data emerging from the trial, in particular as they relate to the safety and wellbeing of participants, and to advise the Trial Steering Committee (TSC) on whether there are any reasons for the trial not to continue. The DMC is the only body involved in the trial that has access to the unblinded (unmasked) comparative data during the trial.

The DMC should advise the TSC, who in turn report to the Sponsor(s) and BHF, as required.

The DMC should have the following terms of reference:

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.
The safety, rights and well-being of the trial participants are paramount.
To determine if additional interim analysis of trial data should be undertaken.
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.
To consider any requests for release of interim trial data and to recommend to the TSC on the advisability of this.
The DMC may be asked by the TSC, the trial Sponsor or BHF, to consider data emerging from other related studies.
Criteria should be agreed (where appropriate) relating to the point at which continuation of the study is considered futile and, in the case of a randomised trial, the DMC would only indicate if these had been passed or not as this would limit the potential for un-blinding.
There are rare occasions when the DMC Chair might be asked by BHF, through the Chair of the TSC, to provide advice based on a confidential interim or futility analysis if serious concerns are raised about the viability of the study.
In rare and exceptional circumstances, the BHF may require direct contact with the Chair of the DMC.

DMC membership

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)

Expert trial statistician(s)

*Independence is defined as:

not part of the same institution as any of the applicants, co-applicants or the Clinical Trials Unit involved in the management of the trial or members of the project team.
not part of the same institution that is acting as a recruitment or investigating centre, including a Patient Identification Centre (PIC). ‘Not part of the same institution’ means not holding either a substantive or honorary contract or title with said institution.
not related to any of the applicants of members of the project team.
no other actual or perceived conflicts of interest e.g. previous or present close working relationship with an applicant that might be perceived as a conflict of interest (e.g. co-applicants on other grants, multiple close co-authorships, previous PhD student of applicant).
for the Chair only – not an applicant on a rival proposal.

If it is proposed that a DMC member is part of the same institution that is acting as a recruitment, investigative centre or PIC, a case should be made for the nomination, and it should be clear what arrangements there are in place at the institution to ensure that there is not a working relationship with the local trial PI or trial team that could potentially influence, or be perceived as being able to potentially influence, the decision making of the DMC member.

It is recognised that the independence status of individual members of the DMC may change during the duration of the project, for example, a member may move from one institution to another, meaning that they would no longer be independent. It is the responsibility of the Chief Investigator to ensure that the funder is notified of such changes, and that the committee maintains the necessary level of expertise and independence.

Criteria for DMC membership

Experience is essential for DMC members to perform their roles properly. Potential DMC members should have:

expertise in the field relevant to the trial
practical experience with conducting clinical trials and a good understanding of the problems and limitations of clinical trials
usually, at least one of the members, in addition to the Chair, should have prior experience of serving on a DMC

BHF approval of DMC members

The BHF must approve the Chair and independent members of the DMC. Please use the DMC membership form to submit your proposed members for approval by email to [email protected]. Please ensure that you provide the following information for each of your proposed members:

Institutional affiliation/s (including any honorary contracts)
An explanation of how the proposed members are independent of the trial, as defined* above
A brief outline of proposed members’ clinical or methodological expertise, experience of clinical trial management/delivery and experience of serving on a DMC

DMC Charter

The DMC should establish a Charter (the DMC Charter) that describes its roles and responsibilities. This is likely to include the DMC terms of reference, timing and format of meetings, reporting to and from the committee, statistical issues and relationships with other committees.

A template for a DMC Charter has been proposed by the DAMOCLES Study Group (Lancet 2005;365;711-22).

DMC meetings

Before the first study site opens to recruitment, the Chief Investigator and Study Coordinator or Manager should have a meeting with the TSC and DMC to finalise the protocol, which should then be sent to BHF. This will include a discussion about finalisation of the protocol, and agreeing the safety and endpoint monitoring requirements of the trial. A joint first meeting of both committees would be good practice.

It is recommended that the DMC should meet before the trial starts, or early in the course of the trial, to discuss the protocol, the trial, any analysis plan, future meetings, and to have the opportunity to clarify any aspects with the principal investigators. The DMC is expected to meet before the study starts if the trial is testing a novel therapy, a high risk therapy, or there are potential serious safety issues associated with the trial.

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 Chair of the DMC. Dates for DMC meetings should be agreed in advance and only altered with agreement of all members.The Chief Investigator should be allowed to request a meeting if there are concerns that need to be raised.

Meetings may consist of open and closed sessions and the membership of each should be agreed by the DMC. Usually only DMC members and those they invite, such as the trial statistician, will attend closed sessions. Open sessions include the DMC members, as well as the Chief Investigator, trial statistician, other investigators and members of the TSC, and representatives of the sponsor, funder or regulator as appropriate. The content of closed and open sessions should be described in the DMC Charter and separate meeting notes should be taken for the different sessions. At the first meeting, members of the DMC should agree the data monitoring process and rules for stopping the trial and ensure that these are in the DMC Charter.

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.

A copy of the DMC’s recommendations to the TSC should be sent to BHF.

DMC processes

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 Chair. The trial statistician may be invited by the Chair 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. The DMC and TSC Charter should specify how disagreement between the DMC and TSC will be managed. The BHF should be kept fully informed about any disagreement, and should be invited to any relevant meetings. In exceptional circumstances, the BHF may directly contact the Chair of the DMC.

Before reporting on the results of the trial the DMC will consider not only the interim results as presented by the trial statistician, but also any major new information from other sources thought to be relevant to the trial (compiled by the Chief Investigator or trial team). It follows that the DMC will not automatically follow pre-assigned statistical rules, although it will be guided by statistical considerations.

Information provided by the DMC is likely to fall into the following categories:

No action required and the trial can continue as planned.
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.
Other outcomes are possible, such as stopping a single arm of a trial, stopping recruitment within one subgroup, extending recruitment or the duration of follow-up, or recommending protocol changes.

Further resources

DAMOCLES Study Group on Data Monitoring Committees
The DAMOCLES Study Group have developed a template for DSMC Charters: DAMOCLES study group et al. A proposed charter for clinical trial data monitoring committees: helping them to do their job well. Lancet 2005;365(9460):711-22.
Declaration of Helsinki: Ethical Principles for Medical Research on Human Subjects
Adopted by the 18th World Medical Assembly, Helsinki, Finland, 1964 and most recently amended by the 75th WMA General Assembly, Helsinki, Finland, October 2024.