Keele CTU
Keele University
TRIAL STEERING COMMITTEE: Terms of Reference
– Insert name of trial and trial acronym
Terms of Reference
1. To monitor and supervise the progress of the ‘insert trial acronym’ towards its interim and overall objectives;
2. To review at regular intervals relevant information from other sources (e.g. other related trials);
3. To consider the recommendations of the Data Monitoring Committee (DMC), and Research Ethics Committee (REC) (where appropriate);
4. To review and endorse any report prepared by the Chief Investigator (CI)/Keele Principal Investigator (PI) on the progress of the trial, prior to this being submitted to the funders (e.g. NIHR and the ARUK).
5. To advise the CI/Keele PI and funder on publicity and the presentation of all aspects of the trial.
Membership:
Independent Chair: insert name
Independent Members: insert name(s)
Lay members: insert name(s)
Principal Investigator (if relevant): insert name
Representatives of the trial team who will attend meetings:
Trial Manager: insert name
CTU Affiliated Statistician: insert name
Chief Investigator: insert name
Where appropriate, observers from the funding organisation and sponsor may also be invited to attend Trial Steering Committee meetings.
The Role of the Trial Steering Committee (TSC)
The role of the TSC is to provide an independent perspective to the overall supervision of the trial and to ensure that the trial is conducted in accordance with Research Governance guidelines, the rigorous standards of Good Clinical Practice and for Clinical Trials of Investigational Medicinal Products (CTIMPs) in line with the UK Medicines for Human Use (Clinical Trials) Regulations 2004 and subsequent amendments, and the EU Clinical Trials Directive. In particular, the TSC should concentrate on:-
- approval of the trial protocol prior to research ethical approval application
- progress of the trial against anticipated timelines and targets, including site set-up and initiation, participant recruitment and retention
- adherence to the trial protocol
- procedures to secure informed consent
- patient safety and the consideration of new information.
Day to day management of the trial is the responsibility of the Chief Investigator(CI)/Keele Principal Investigator(PI), insert name, and he/she has established a Trial Management Group to assist with this function.
Trial Steering Committee Meetings
Meetings of the TSC will be organised by the CI/Keele PI before the start of the trial to approve the final protocol, which will then be submitted for review by HRA (and any other applicable regulatory body. After the initial meeting the TSC will meet at least annually. There may be periods when more frequent meetings are necessary and may be called either by the Chair of the TSC or the CI/Keele PI.
Responsibility for organising TSC meetings lies with the CI/Keele PI. Papers for meetings will be circulated well in advance of the meeting rather than tabled and an accurate minute of the meeting will be prepared by the Trial Manager and agreed by all members. The minutes will be available in a timely manner.
Patient Safety
In all the deliberations of the TSC 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. The TSC should ensure that the protocol demands, where possible and appropriate given the trial design, freely given informed consent from every trial participant. The TSC should look closely at the patient information provided and advise the investigators on its completeness and suitability.
Complaints Procedures and Compensation for Participants
The TSC should ensure that participants in the trial have access to information that clearly explains the arrangements which are in place if they are unhappy with any aspect of the conduct of the trial, and the arrangements in place in the case of negligent or non-negligent harm to participants.
Progress of the Trial
It is the role of the TSC to monitor the progress of the trial and to maximise the chances of completing it within the timescale, which has been set out in the protocol and agreed by the funders. At the first TSC meeting, targets for gaining regulatory approvals, site(s) set-up and initiation, participant recruitment, data collection, etc. will be agreed with the CI/Keele PI. These targets should not be "set in stone" but are designed to permit adequate monitoring of trial progress. The TSC should agree which data, based on the targets set, should be presented at each TSC meeting.
Where the CI/Keele PI is required to submit a report to the funder, this report should be endorsed by the TSC and should stand alone and contain sufficient data to allow the funder to judge progress in the trial without the need to refer back to the original grant proposal, and inform the funder of any new information that has a bearing on safety or ethical acceptability of the trial or any significant complaints arising, with a justification of any decisions taken on the matter. If progress of the trial suggests that an extension of time may be necessary, the TSC should ensure that funders are notified at the earliest opportunity. In such cases, the TSC will work in conjunction with the DMC to provide the appropriate evidence, from this and other trials, to demonstrate that all practicable steps have been taken to improve recruitment and to keep within the agreed duration of the grant, and to advise on the likelihood that continuation of the trial will allow detection of an important effect.
Adherence to Protocol
The full trial protocol will be presented as an agenda item at the first TSC meeting. The TSC should help ensure that there are no major deviations from the trial protocol. If the trial team recommend any material changes to the protocol during the course of the trial, approval should be sought from the TSC, the HRA (and any other appropriate regulatory body), and the host NHS site, and the funder should be informed.
Consideration of New Information
The TSC should consider new information relevant to the trial including reports from the DMC and the results of other relevant studies. It is the responsibility of the CI/ Keele PI, the TSC Chair and independent members of the TSC to bring to the attention of the TSC any results from other studies of which they are aware that may have a direct bearing on the future conduct of the trial.
On consideration of this information, the TSC should recommend appropriate action, such as changes to the trial protocol, additional patient information, or stopping or extending the study. The rights, safety and well-being of the trial participants (present and future) should be the most important considerations in these deliberations.
The Chair of the TSC should formally report their recommendations to the sponsor of the trial, and provide advice to the CI and host institution.
It is the responsibility of the trial team to notify any serious adverse events (SAEs) to the CI/ Keele PI and to the host site, and to follow agreed procedures to respond to any SAEs (see SOP 20 Safety Reporting and Pharmacovigilance). The CI/ Keele PI is responsible for ensuring that the TSC and DMC are kept informed of any SAEs. In the case of unexpected SAEs the Chair of the TSC and the DMC should be notified and, where appropriate, the regulatory authority.
Dissemination and Implementation of Results
The TSC should ensure that appropriate efforts are made to ensure that the results of the trial are adequately disseminated (including to the participants, should they wish to receive them) and due consideration is given to the implementation of the results into clinical practice.
Data Monitoring and Ethics Committee (DMC)
A DMC has been established for the insert trial acronym Trial. The DMC are collectively responsible for:-
- monitoring the progress of the trial from the start to the end of data collection
- scrutinising recruitment
- scrutinising randomisation
- scrutinising protocol compliance and adherence
- scrutinising follow up
- assessing adverse events
The DMC is a completely independent team with relevant knowledge and expertise in the conduct and methodological aspects of clinical trials, and who are responsible for ensuring the integrity and appropriate running of the trial. The DMC will review confidential reports prepared by the CTU affiliated statistician in an agreed format bi-annually. The DMC members will liaise with one another by email contact and/or by telephone and/or by face-to-face contact, as deemed necessary, to agree feedback on confidential trial reports.
On the basis of all information and feedback received, the DMC Chair will prepare a confidential overview of the report provided by the CTU affiliated statistician and submit this to the Chair of the TSC and to the CI/ Keele PI, providing advice on:
q Whether the trial should continue or not. If the DMC recommends that the trial is stopped at any point, the funding bodies should be notified. It is the responsibility of the TSC to decide whether or not to act upon the information received from the DMC.
q Whether the design of the trial needs amending, if this is deemed appropriate in the light of accumulating data from the study, or from information available from other sources. It is the responsibility of the TSC and the CI/ Keele PI to respond to such advice.
The DMC is the only body involved in the trial that can request access to unblinded or unmasked comparative data, but unblinded data will not be available to the TSC or any investigators involved in the trial. Contact between the TSC and DMC will be via the chair persons of the two groups.
Template for TSC meeting agendas and reports
Presented below are guidelines on the information that should be provided by investigators for discussion at TSC meetings and included in the CI/ Keele PI’s report to the TSC. It is suggested that the headings listed below should provide a basis for the agenda of the meetings and form the template for the report.
These headings may not be appropriate at every stage of the trial.
Trial Steering Committee Agenda- insert trial acronym
1. Title of Trial
2. Funding source(s) and Grant No.
3. Sample size sought
4. Date recruitment started
5. Proposed date for recruitment end
6. Actual recruitment rate versus target rate (by month/quarter)
7. Acceptance rate, as a proportion of
i) those invited to participate, and
ii) if known all eligible participants
8. Quarterly/monthly forecasts of recruitment for the planned remainder of the trial
9. Losses to follow-up
i) as a proportion of those entered, and
ii) per month/quarter
10. No. for whom follow-up has been completed successfully (or still being successfully followed-up)
11. Scrutiny of adverse events
12. Completeness of data collected
13. Any available results (pooled)
14. Any organisational problems
15. Issues specific to individual trials (to be specified by the Steering Committee)
TSC member name ………………………………………………………………………………….
Signed………………………………………………………. Date ………………………………
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Standard Template for TSC Terms of Reference. Version 2.0, 06-Sept-2016.