CHARTER FOR DATA MONITORING COMMITTEE FOR THE CONFIdeNT STUDY
DRAFT FOR APPROVAL
Introduction
Study name
CONFIDeNT: CONtrol of Faecal Incontinence using Distal NeuromodulaTion.
Study registration
ISRCTN88559475.
Objectives of the study
To determine the effectiveness of PTNS versus sham electrical stimulation, based on (primary outcome) reductions in weekly FIEs and on (secondary outcomes) improvements in validated incontinence scores and other symptoms and quality-of-life measures.
Purpose of charter
The purpose of this document is to describe the roles and responsibilities of the independent Data and Monitoring Ethics Committee (DMEC) for the CONFIDeNT study, including the timing of meetings, methods of providing information to and from the TSC, frequency and format of meetings and statistical issues.
Roles and responsibilities of the Data Monitoring and Ethics Committee
Broad statement of aim of committee
To protect and serve study participants (especially regarding safety) and to assist and advise the chief investigator so as to protect the validity and credibility of the trial.
Terms of reference
The DMEC will receive and review interim results of the study.
The DMEC is responsible to the TSC of the study. Although it may choose to communicate interim results or make recommendations, the final decisions about the study rest with the TSC.
During the period of recruitment to the study, data will be supplied to the Chair of the DMEC as frequently as is requested. Meetings of the committee, either in person or by phone, will be arranged periodically, as considered appropriate by the Chair.
In the light of the interim data, the DMEC will inform the TSC if, in their view, there is proof beyond reasonable doubt that the data indicate that the treatment under investigation is either clearly indicated or clearly contraindicated.
If the DMEC does choose to inform the TSC that in their view the situation described above pertains, the TSC will consider modifying or stopping intake into the study. Unless modification or cessation is recommended by the DMEC, however, the TSC, collaborators and administrative staff (except staff who produce the confidential analyses) will remain ignorant of the interim results.
Collaborators, and all others associated with the study, may write directly to the Chair of the DMEC, to draw attention to any concern they may have about the possibility of harm arising from the use of the treatment under study, or about any other matters that may be relevant.
Specific roles of Data Monitoring and Ethics Committee
These will include interim reviews of the trial’s progress including:
updated figures on recruitment and losses to follow-up
data quality, including completeness and adherence to protocol by participants and investigators
evidence for treatment harm, for example safety data and adverse events
advice on any protocol modifications suggested by investigators or sponsors.
Before or early in the trial
Before the start of recruitment, the TSC met with the DMEC to discuss various aspects of the trial and protocol. All DMEC members had the opportunity to see the study protocol, and will have the opportunity to comment on the contents of this charter.
Among the points raised, it was suggested that a draft statistical analysis plan be drafted for the next DMEC meeting. Other points raised, relevant to the DMEC, are mentioned later in this document.
Composition of Data Monitoring and Ethics Committee and relationship to trial steering committee
Membership and size
The members are independent of the trial, and include a clinician and a statistician.
The members of the CONFIDeNT DMEC are:
Professor Dion Morton (chair)
Professor of Surgery
Academic Department of Surgery
University of Birmingham
Queen Elizabeth Hospital
Mindelsohn Way
Edgebaston
Birmingham, B15 2WB
E-mail: XX
Professor Elaine Denny (independent member)
Professor of Health Sociology
Birmingham City University
City North Campus
Birmingham, B42 2SU
E-mail: XX
Dr Dan Altmann (independent statistician)
Senior Lecturer in Medical Statistics
Department of Medical Statistics
London School of Hygiene & Tropical Medicine
Keppel Street
London, WC1E 7HT
E-mail: XX
The responsibilities of the trial statistician
The trial statistician, Dr Stephen Bremner, in consultation with the senior trialstatistician Professor Sandra Eldridge, will organise the interim reports to the DMEC. These reports will contain unblinded data, although the trial statistician will not see the unblinded version. It is not expected that the trial statistician will need to participate in DMEC meetings, but he should be available to respond to any queries arising from the interim reports.
Payment to Data Monitoring and Ethics Committee members
Members will be reimbursed for travel to and from DMEC meetings if required.
Competing interests
Data Monitoring and Ethics Committee members should disclose to the TSC any competing interests, not restricting to financial matters. DMEC members will respect the confidentiality of the interim reports, and will not use interim results to influence or inform financial trading. The format for a short competing interests form is given in Annex 1, and should be completed by DMEC members and returned to the chief investigator [CI].
Organisation of Data Monitoring and Ethics Committee meetings
Timing of data monitoring and ethics committee meetings
The first DMEC meeting should be at 5 months, and will be held in Birmingham; subsequently meetings will be held 3 to 4 weeks prior to planned TSC meetings. The format of subsequent DMEC meetings will be decided by DMEC.
Trial documentation and procedures to ensure confidentiality and proper communication
It is anticipated that the first interim report for DMEC, organised by the trial statistician, should contain data presented, where possible, by unblinded trial allocation group, to include (1) recruitment flow chart (showing attendance at scheduled visits and any reported non-adherence and withdrawal from the trial); (2) primary and secondary outcomes; and (3) adverse events and any other safety-related data. A dummy report before the first DMEC meeting, although helpful, is not necessary. Changes to format or content may be requested by DMEC for subsequent DMEC meetings.
Access to the accumulating data and interim results
Data and Safety Monitoring Committee members do not have the right to share confidential information with anyone outside the DMEC, including the CI and named applicants.
Responsibility for identifying and circulating external evidence
Identification and circulation of external evidence (e.g. from other trials/systematic reviews) is not the responsibility of the DMEC members. The TSC will usually collate any such information if appropriate.
To whom the data monitoring and ethics committee will communicate the decisions/recommendations that are reached
The DMEC will report its recommendations in writing to the TSC, copying to the trial statistician, in time for consideration at the next TSC meeting. It is hoped and anticipated that, routinely, if the trial is to continue largely unchanged, then a note from the DMEC Chair back to TSC along the lines given in Annex 2 will be sufficient response.
Ensuring safety of confidential papers
The DMEC members should store interim report papers safely after each meeting so they may check the next report against them. After the trial is reported, the DMEC members should destroy all interim reports.
Decision-making
What decisions/recommendations will be open to the Data Monitoring and Ethics Committee?
Possible recommendations could include:
no action needed, trial continues as planned
early stopping as a result, for example, of clear benefit or harm of a treatment, futility or external evidence
extending recruitment (based on actual control arm response rates being different to predicted) or extending follow-up
sanctioning and/or proposing protocol changes.
Statistical methods
Any planned interim analyses should be tabled by the trial statistician before the first DMEC meeting for discussion and agreement.
How decisions or recommendations will be reached within the Data Monitoring and Ethics Committee
Data Monitoring and Ethics Committee members must agree on a process of decision-making, including whether or not there will be voting or other formal or informal methods of achieving consensus.
Every effort should be made by the DMEC to reach a unanimous decision. If the DMEC cannot achieve this, a vote may be taken, although details of the vote should not be routinely included in the report to the TSC, as these may inappropriately convey information about the state of the trial data. It is important that the implications (e.g. ethical, statistical, practical, financial) for the trial be considered before any recommendation is made.
When the Data Monitoring and Ethics Committee is quorate for decision-making
Owing to the relatively small size of the DMEC, decisions should involve all three members, but not necessarily at a face-to-face meeting: teleconference or e-mail contact may be sufficient. DMEC members who will not be able to attend a planned face-to-face meeting may pass comments to the DMEC Chair for consideration during any discussions.
Reporting
Minutes of meetings
Separate minutes of DMEC meetings will be taken by the Chair of the DMEC. The DMEC Chair must sign off all minutes.
What will be done if there is disagreement between the Data Monitoring and Ethics Committee and the trial steering committee?
If the DMEC has serious problems or concerns with the TSC decision, a meeting of these groups should be held. The information to be shown would depend upon the action proposed and the DMEC’s concerns. Depending on the reason for the disagreement confidential data may have to be revealed to all those attending such a meeting. The meeting should be chaired by a senior member of the TSC or an external expert who is not directly involved with the trial. The funder may be invited to such meetings.
After the trial
Publication of results
At the end of the trial there will be a meeting to allow the DMEC to discuss the final data with the chief investigator and give advice about data interpretation.
The information about the Data Monitoring and Ethics Committee that will be included in published trial reports
Data Monitoring and Ethics Committee members will be named and their affiliations listed in the main trial report, unless they explicitly request otherwise. A brief summary of the timings and conclusions of DMEC meetings should be included in the body of this paper.
Will the Data Monitoring and Ethics Committee have the opportunity to comment on publications before submission?
The DMEC will be given an opportunity to read and comment on any publication before it is submitted.
Constraints on Data and Safety Monitoring Committee members divulging information about their deliberations after the trial has been published
The DMEC may discuss issues from their involvement in the trial 12 months after the primary trial results have been published.
Annex 1. Competing interests form
Potential competing interests of DMEC members for CONFIDeNT, ISRCTN88559475.
The avoidance of any perception that members of a DMEC may be biased in some fashion is important for the credibility of the decisions made by the DMEC and for the integrity of the CONFIDeNT study. Possible competing interests should be disclosed: in many cases simple disclosure should be sufficient. Otherwise, the DMEC member should remove the conflict or stop participating in the DMEC. lists potential competing interests.
Potential competing interests
Please complete the following section and return to the Chief Investigator.
______ No, I have no competing interests to declare
______ Yes, I have competing interests to declare (please detail below)
Please provide details of any competing interests:
_____________________________________________________________
Name: _______________________________
Signed: ______________________________ Date: ________________
Annex 2. Suggested report from the Data Monitoring and Ethics Committee to the Trial Steering Committee where no recommendations are being made
BOX 1
Suggested report from the DMEC to the TSC where no recommendations are being made
[Insert date]
To: Chair of Trial Steering Committee
Dear [Chair of Trial Steering Committee]
The Data Monitoring and Ethics Committee (DMEC) for the [insert trial name] trial met on [meeting date] to review its progress and interim accumulating data. [List members] attended the meeting and reviewed the report.
The trial question remains important and, on the basis of the data reviewed at this stage, we recommend continuation of the trial according to the current version of the protocol [specify protocol version number and date] with no changes.
We shall next review the progress and data [provide approximate timing]
Yours sincerely,
[Name of meeting Chair]
Chair of Data Monitoring and Ethics Committee
On behalf of the DMEC (all members listed below)
DMEC members:
(1) [Insert name and role]
(2) [Insert name and role]
(3) [Insert name and role]
