Trial Steering Committee guidelines

It is British Heart Foundation (BHF) policy that a Trial Steering Committee should be set up for each of its multicentre clinical trials. The terms of reference and guidelines are below. 

 

The Steering Committee should have the following terms of reference:

1. To monitor and supervise the progress of the study towards its interim and overall objectives.

2. To review at regular intervals (annual / bi-annual / quarterly) relevant information from other sources (e.g. other related studies).

3. To consider the recommendations of the Data Monitoring Committee (DMC) where one exists as defined by the Sponsor organisation based on an assessment of risk.

4. In the light of 1, 2 and 3 to be sure that the BHF is well informed, through Chief Investigator reporting, on the progress of the study.

Steering Committee membership

The membership should be limited and include:

  • an independent Chairperson (not involved directly with the study other than as a member of the Steering Committee)
  • two or more other independent expert members (clinical and/or methodological)
  • one or two principal investigators (one should be the Chief Investigator)
  • where possible a lay representative
  • observers from the BHF and the Sponsor should be invited to all meetings.

The trial manager, trial co-ordinators, statisticians etc should attend meetings as appropriate.

The BHF must approve the Chair of the Steering Committee and the two independent members.

Study management

The role of the Steering Committee is to provide overall supervision of the study on behalf of BHF and the Sponsor. The Steering Committee should concentrate on the progress of the study, adherence to the protocol, patient safety and consideration of new information relevant to the research question.

Day to day management of the study is the responsibility of the Investigators, and the Chief Investigator may wish to set up a separate Trial Management Group (TMG) to assist with this function.

The Steering Committee should provide advice, through its Chair, to the Chief Investigator(s), the Trial Sponsor, the BHF and the Host Institution on all appropriate aspects of the study.

Data Monitoring Committee

The Sponsor should complete a risk assessment to determine the need for a DMC; if required this should be constituted. The Steering Committee should establish the reporting logistics between itself and the DMC, which should meet regularly to review the data and results of any interim analyses. Members of the DMC should be independent of both the Study Management and Steering Committees.

Steering Committee meetings

Before the study starts, the Chief Investigator (or Study Coordinator or Manager) should organise a meeting of the Steering Committee to finalise the protocol, which should then be sent to BHF. The Steering Committee should then meet at least annually (bi-annual/quarterly), although there may be periods when more frequent meetings are necessary. Meetings should be organised by the Chief Investigator. Papers for the meeting should be circulated well in advance. Accurate minutes should be prepared by the Chief Investigator and agreed by all the members and a copy sent to BHF.

Patient safety

In all of the deliberations of the Steering Committee the rights, safety and well-being of the study participants are the most important considerations and should prevail over the interests of the science and society. The Steering Committee should advise the investigators on the completeness and suitability of the patient information provided as part of the process of obtaining freely given informed consent from each subject.

Good Clinical Practice

The Steering Committee should endeavour to ensure that the study is conducted at all times to the standards set out in Guidelines for Good Clinical Practice (GCP) e.g. MRC GCP.

Adherence to protocol

The Steering Committee should ensure that there are no major deviations from the study protocol. The full protocol should be presented and agreed at the first Steering Committee meeting. Any subsequent substantial amendments to the protocol must be approved by the Steering Committee and ethics and be notified to BHF and the revised protocol submitted for reference.

Progress of the study

The role of the Steering Committee is to monitor the progress of the study and to maximise the chances of completing it within the timescale agreed by BHF. At the first Steering Committee meeting, targets for recruitment, data collection, compliance etc. should be agreed with the Chief Investigator. Based on these targets, the Steering Committee should agree a set of data that should be presented at each meeting.

The Chief Investigator is required to submit progress reports, to a defined template, to BHF at timelines defined on award of the grant and on subsequent review of study progress. The progress report does not have to be endorsed by the Steering Committee but should be submitted with their awareness. The report should be stand alone and contain sufficient information to enable BHF to assess the progress of the study without the need to refer back to the original grant application.

The initial progress reports should include information about progress in attaining relevant regulatory approvals and, once the study has commenced, information about recruitment status. The progress report should inform BHF of any new information that has a bearing on safety or ethical acceptability of the study or any significant complaints arising, with a justification for the decisions taken.

For clinical trials, the progress report will be reviewed by the Clinical Studies Committee to assess the performance and deliverability of the study and, where appropriate, to consider whether funding should be continued. 

Consideration of new information

The Steering Committee should consider new information relevant to the study including reports from the DMC. It is the responsibility of the Chief Investigator, the Chair and other independent members to bring results from other studies that may have a direct bearing on future conduct of the study to the attention of the Steering Committee. On consideration of this information the Steering Committee should recommend appropriate action, such as changes to the protocol, additional patient information or stopping the study. The rights, safety and well-being of the study participants should be the most important consideration.

Adverse events

It is the responsibility of the investigators to report regularly the extent of serious adverse events to the Steering Committee and the DMC. In the case of unexpected SAEs, the Chair of the Steering Committee should be notified and, where appropriate, the regulatory authority.

Timeline extensions

BHF will consider proposals for no cost extensions of grants for clinical studies in exceptional circumstances. If progress on the study suggests that additional time may be required, the Steering Committee should notify the BHF at the earliest opportunity, and then under Steering Committee agreement and direction, the Chief Investigator should submit such requests to BHF. Extension of funding duration will require evidence of support from the Steering Committee that all practicable steps have been taken e.g. to improve recruitment and keep within the agreed duration of the grant.

The DMC, where in existence, should be asked to advise the Steering Committee, and may be required to provide information on the availability of data collected to date (from this and other studies) and advise on the likelihood that continuation of the study will allow detection of an important effect. This should be done using methods that do not unblind the study.

Supplementary funding

In exceptional circumstances BHF will consider proposals for funded extension of grants for clinical studies. If progress on the study suggests that additional funding may be necessary, under Steering Committee agreement and direction, the Chief Investigator should submit such requests to the BHF after consulting with the BHF office.

Requests for additional funding will be assessed by the appropriate BHF Research Grants Committee, which will require evidence from the Steering Committee that all practicable steps have been taken e.g. to improve recruitment and keep within the agreed duration of the grant.

The DMC, where in existence, should be asked to advise the Steering Committee, and may be required to provide information on the availability of data collected to date (from this and other studies) and advise on the likelihood that continuation of the study will allow detection of an important effect. This should be done using methods that do not unblind the study.