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, including the UK arm of an international trial.

The terms of reference and guidelines are below:

The Steering Committee should have the following terms of reference:

1. To provide trial oversight and supervision on behalf of the Sponsor and BHF.
2. To monitor and supervise the progress of the study towards its interim and overall objectives.
3. To ensure that the trial is conducted according to the guidelines for Good Clinical Practice (GCP), Research Governance Framework for Health and Social Care and all relevant regulations and policies.
4. To review at regular intervals (annual / bi-annual / quarterly) relevant information from other sources (e.g. other related studies).
5. 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
6. To advise the Chief Investigator, Sponsor and BHF on all aspects of the study.
7. To make sure that the BHF is well informed, through Chief Investigator reporting, on the progress of the study.
8. In all the deliberations of the Steering Committee, the rights, safety and well-being of the trial participants are the most important considerations and should prevail over the interests of science and society.

Steering Committee membership

The membership should usually be limited and include:

• an independent* Chairperson (not involved directly with the study other than as a member of the Steering Committee). The Steering Committee Chair does not need to be a study-specific content expert but needs to ensure that sufficient content expertise is available for the group to perform its oversight function effectively.
• two or more independent* expert members, at least one of whom should be a statistician or a clinical trials methodologist with expertise in the main methods used in the study, and others with clinical or other expertise relevant to the project.
• one or two principal investigators (one should be the Chief Investigator)
• where possible a lay representative with lived experience of the condition under investigation. Lay representatives should not have been involved in designing the trial or applying for funding, and should not be a current patient of a clinician on the trial team. 
• observers from the BHF and the Sponsor should be invited to all meetings.

Independent members should ideally be from different geographical locations across the UK, and can be based at institutions outside the UK. 

The Chair and at least 50% of Steering Committee members must be independent.

The trial manager, trial co-ordinators, statisticians etc should also attend meetings as appropriate (either ‘in attendance or as observers’).

Only appointed members (i.e. not those ‘in attendance or observers’) will be entitled to vote (irrespective of their level of independence) and the Chair will have a casting vote. 

*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 perceived conflicts of interest, e.g. previous 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 an independent member is part of the same institution that is acting as a recruitment, investigative centre or PIC, 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 independent TSC member.

It is recognised that the independence status of individual members of the TSC 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.

If the Steering Committee is for an international trial led from the UK:

• Independent membership should be international (i.e. independent members should not all be from a single country). 
• The national principal investigators from the major recruiting countries should attend the TSC either as observers (in attendance) or as non-independent members. 

If the Steering Committee is for the UK arm of an international arm led from outside the UK: 

• The UK principal investigator or a representative of the UK trial should attend the international Steering Committee so that the UK Steering Committee is informed of any actions and minutes from the international TSC and DMC.

BHF approval of TSC members

The BHF must approve the Chair and independent members of the Steering Committee. Please use the TSC 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 TSC.

Steering Committee Charter

The Steering Committee should establish a Charter (the TSC/Steering Committee Charter) that describes its roles and responsibilities. This should include the terms of reference, Steering Committee membership, purpose, timing and format of meetings, decision making, reporting to and from the committee, statistical issues and relationships with other committees. The charter should also describe the procedures for ensuring confidentiality and the content outline of the Steering Committee meeting progress reports.

The TSC Charter should be drafted in advance of the first TSC meeting and circulated to the TSC members.

Quorum

Every effort should be made to ensure that all Steering Committee members can attend the meetings. The Chief Investigator should attend the meetings except in exceptional circumstances, and no major decision should be made without their involvement. 

The Steering Committee Charter should outline the minimum quoracy for any Steering Committee meeting to conduct business. To have a quorum for decision making, the number of independent members (with voting rights) should exceed the number of non-independent members (with voting rights). The Chair and the Chief Investigator should also be present. 

Only appointed members will be entitled to vote (irrespective of their level of independence) and the Chair will have a casting vote.

The Chair should follow up with the absent members of the committee after the meeting to ensure they agree with the decisions made. If quorum requirements are not met, the meeting should be rescheduled.

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 Data Monitoring Committee (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.

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. See BHF guidance about DMCs.

Steering Committee 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. 

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.

The Steering Committee should then meet at least annually (bi-annual/quarterly), although there may be periods when more frequent meetings are necessary. More regular meetings are typically required during key stages of the trial. Additional meetings may be held at appropriate timepoints relating to data collection or in response to critical milestones.  

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.

Steering Committee meetings should be scheduled to follow shortly after the DMC meetings so that reports from the DMC can be considered if appropriate.

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 the Guidelines for Good Clinical Practice (GCP), Research Governance Framework for Health and Social Care and all relevant regulations and policies.

Adherence to the protocol

The full protocol should be presented and agreed at the first Steering Committee meeting, which should then be sent to BHF. A representative of the DMC should attend the meeting to feed into the discussion about finalisation of the protocol, including safety and endpoint monitoring. A joint first meeting of both committees is good practice. If there have been major changes to the final protocol from the awarded BHF grant application, BHF should be informed of these changes for approval.

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 to BHF for approval. 

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.

As well as monitoring recruitment of participants against milestones, the Steering Committee should monitor the overall demographics of the study participants (such as age, sex, ethnicity, and any other relevant characteristics) versus expected demographics of the population that is affected by the condition being studied or that needs the healthcare intervention.

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.

The progress report should outline any substantial amendments to the protocol. The latest version of the protocol should be submitted to BHF with the progress report. 

For clinical trials supported  by a Clinical Study Grant, 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.

Publication of results

An independent member of the Steering Committee can be a named author on a trial publication that is written after data lock and after the delivery of the trial.  Contribution as a named author on a publication should not influence the decision making of the independent member on the TSC. The TSC should have the opportunity to comment on trial publications, and at a minimum, on the main trial report. The TSC membership, names and affiliations, should be included, where possible, in the acknowledgements section of publications with the permission of the members. 

Dissemination and Implementation of results

The Steering Committee should ensure that appropriate efforts are made to disseminate the results of the study (including to the participants, should they wish to receive them) and due consideration is given to the implementation of the results into clinical practice.

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.

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 for clinical studies supported by a Clinical Study Grant will be assessed by the Clinical Studies 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 and funding envelope of the grant.

Stopping a trial early 

BHF may independently recommend that a study should be terminated early due to concerns expressed by its committee about deliverability, conduct, or other aspects of the study. The BHF has the right to withdraw funding for the trial on recommendation by its committee. 

In such instances the BHF will inform the Chief Investigator, the Chair of the Steering Committee and the Sponsor of the Committee’s recommendations, and may request a meeting with the Chief Investigator and members of the trial team to discuss the committee’s decision. The Chair of the Steering Committee and the Sponsor may be invited to attend the meeting. 

Further resources

JA Lane, C Gamble, WJ Cragg, D Tembo, MR Sydes. A third trial oversight committee: Functions, benefits and issues. Clinical Trials 2020;17():106-112.

NL Harman, EJ Conroy, SC Lewis et al. Exploring the role and function of trial steering committees: results of an expert panel meeting. Trials 2015; 16:597