DATA MONITORING COMMITTEE (DMC)
CHARTER FOR THE
<<NAME>> TRIAL
<<Insert trial logo here>>
<<Insert Full Trial Name here>>
REC reference:
Sponsor:
Funding body:
ISRCTN:
EudraCT number:
Version:
<<Name>> Data Monitoring Committee (DMC) charter
1
Version 1.0, 5 October 2013
1.
INTRODUCTION
3
2.
PRIMARY RESPONSIBILITIES OF THE DMC
3
3.
ORGANISATIONAL DIAGRAM
3
4.
MEMBERSHIP OF THE DMC
4
Members
Conflicts of Interest
4
4
5. TIMING AND PURPOSE OF THE DMC MEETINGS
5
Initial DMC Meeting
Subsequent DMC Meetings
On-going Safety/Trial Integrity Review
Final Trial Meeting
5
5
5
6
6. PROCEDURES TO ENSURE CONFIDENTIALITY & PROPER COMMUNICATION
Open Session
Closed Sessions
Open and Closed Reports
Minutes of the DMC meeting
Recommendations to the Trial Steering Committee (TSC)
6
6
6
7
7
8
7. STATISTICAL MONITORING GUIDELINES
8
8. CONTENT OF THE DMC’S OPEN AND CLOSED REPORTS
9
Open Statistical Report: An Outline
Closed Statistical Report: An Outline
9
9
9. REFERENCE DOCUMENTS
9
DMC Charter Signature Page
<<Name>> Data Monitoring Committee (DMC) charter
10
2
Version 1.0, 5 October 2013
1. INTRODUCTION
This charter is for the Data Monitoring Committee (DMC) for the <<Name>> trial.
The charter defines the responsibilities of the DMC, its relationship with other trial
components, its membership, and the purpose and timing of its meetings. The charter also
provides the procedures for ensuring confidentiality and proper communication, the
statistical monitoring guidelines to be implemented by the DMC, and a proposed outline of
the content of the Open and Closed Reports that will be provided to the DMC.
2. PRIMARY RESPONSIBILITIES OF THE DMC
The DMC will be responsible for safeguarding the interests of trial participants, assessing the
safety and efficacy of the interventions during the trial, and for monitoring the overall
conduct of the clinical trial. To contribute to enhancing the integrity of the trial, the DMC
may
also
formulate
recommendations
relating
to
the
selection/recruitment/retention/safety of participants, their management, improving
adherence to protocol-specified regimens and retention of participants, and the procedures
for data management and quality control.
The DMC will be advisory to the Trial Steering Committee (TSC). The TSC will be responsible
for promptly reviewing the DMC recommendations, to decide whether to continue or
terminate the trial, and to determine whether amendments to the protocol or changes in
trial conduct are required.
3. ORGANISATIONAL DIAGRAM
The following diagram shows the flow of information between the DMC and the other committees
and functional areas involved in the trial.
Data Monitoring Committee (DMC)
Open & Closed
reports
DMC
Trial Statistician
recommendations
Open report
Open report
Trial Coordinating Centre
Trial Steering Committee
Recommendations
The DMC for this trial is composed of independent members defined in section 4.
<<Name>> Data Monitoring Committee (DMC) charter
3
Version 1.0, 5 October 2013
Warwick Clinical Trials Unit will provide the database to the trial statistician and will be party to
presentation of the open report. Relevant staff (Chief Investigator, Trial Coordinator) responsible for
the serious adverse event (SAE) monitoring will also be given a copy of the open report and will be
present at the DMC open sessions.
4. MEMBERSHIP OF THE DMC
Members
The DMC is an independent multidisciplinary group consisting of at least one biostatistician and
clinician that, collectively, have experience in the management of patients with <<disease area>>,
and in the conduct and monitoring of randomised clinical trials.
DMC Chair:
<<Name>>
<<Address>>
<<Email>>
DMC Member:
<<Name>>
<<Address>>
<<Email>>
DMC Member:
<<Name>>
<<Address>>
<<Email>>
Conflicts of Interest
The DMC membership has been restricted to individuals free of apparent significant conflicts of
interest. The source of these conflicts may be financial, scientific or regulatory in nature. Thus,
neither trial investigators nor individuals employed by the sponsor, nor individuals who might have
regulatory responsibilities for the trial, are members of the DMC. Members will have to sign the
DMC Charter Signature Page which includes a ‘DMC members disclosure agreement’ and a
‘Confidentiality Agreement’ that states that members do not have any conflicts of interest and that
all information discussed within the closed reports provided from the trial statistician will remain
confidential. Any concerns the DMC may have should be communicated via the DMC
recommendations directly to the TSC.
<<Name>> Data Monitoring Committee (DMC) charter
4
Version 1.0, 5 October 2013
Any DMC members who develop significant conflicts of interest during the course of the trial should
resign.
DMC membership is to be for the duration of the clinical trial and members are expected to
attend all meetings. If any members leave or fail to attend consecutive meetings, the DMC Chair,
CI, funding body and TSC, will liaise to appoint a replacement.
The DMC should not discuss confidential issues arising from their involvement in the trial until 12
months after the primary trial results have been published, unless permission is agreed with the TSC.
5. TIMING AND PURPOSE OF THE DMC MEETINGS
Initial DMC Meeting
The first DMC will be held as stated in the <<Name>> protocol (Version x.x, dated dd/mmm/yyyy),
At the first DMC meeting members will be provided with a copy of the trial protocol,
the DMC
Charter and Case Report Forms. At this initial meeting the chairman will invite the Chief and/or
Principal Investigators to introduce the trial and there will be an opportunity to highlight any
concerns within the protocol. The DMC will receive Open and Closed Reports at subsequent
meetings, after it has been agreed with the DMC and the TMG what is required in these reports.
Subsequent DMC Meetings
The DMC meetings will discuss Early Safety/Trial Integrity. If required, interim analyses will be
planned with the agreement of the DMC.
Confidential reports containing recruitment, protocol compliance, safety data and interim analyses
of outcomes (not formally tested outside of the trial statistical analyses plan, to be agreed with the
DMC) will be reviewed by the DMC.
On-going Safety/Trial Integrity Review
In addition to the DMC meetings, on-going safety/trial integrity review meetings will be held inperson or by teleconference to review available data relating to patient safety, efficacy and quality
of trial conduct. The content of the statistical reports provided to the DMC is outlined in section 7.
<<Name>> Data Monitoring Committee (DMC) charter
5
Version 1.0, 5 October 2013
Final Trial Meeting
A final trial meeting will be held based on the availability of the final trial data and DMC members. If
the trial is terminated based on the recommendations of the DMC, no final trial meeting is required.
6. PROCEDURES TO ENSURE CONFIDENTIALITY & PROPER COMMUNICATION
To enhance the integrity and credibility of the trial, procedures will be implemented to ensure the
DMC has sole access to evolving information from the clinical trial regarding comparative results of
efficacy and safety data, aggregated by treatment arm. An exception will be made to permit access
to the trial statistician who will be responsible for serving as a liaison between the database and the
DMC. The trial’s Trial Coordinator will be provided with immediate access on an on-going basis to
patient-specific information on serious adverse events (SAEs) to satisfy the standard requirement for
prompt reporting to the regulatory authorities.
At the same time, procedures will be implemented to ensure proper communication is achieved
between the DMC and the trial investigators and sponsor. To provide a forum for exchange of
information among various parties who share responsibility for the successful conduct of the trial, a
format for Open Sessions and Closed Sessions will be implemented. The intent of this format is to
enable the DMC to preserve confidentiality of the comparative efficacy results while at the same
time providing opportunities for interaction between the DMC and others who have valuable
insights into trial-related issues.
Open Session
In order to allow the DMC to have adequate access to information provided by trial investigators, a
joint session between these individuals and DMC members (called an Open Session) will be held
before the Closed Sessions. With this format, important interactions are facilitated through which
problems affecting trial integrity can be identified and resolved. These individuals will either be
present at the DMC meeting or be provided with teleconference dial-in information
Closed Sessions
Sessions involving only DMC membership and the trial statisticians who generated the Closed
Reports (called Closed Sessions) will be held to allow discussion of confidential data from the clinical
trial, including information about the relative efficacy and safety of interventions. In order to ensure
<<Name>> Data Monitoring Committee (DMC) charter
6
Version 1.0, 5 October 2013
that the DMC will be fully informed in its primary mission of safeguarding the interest of
participating patients, the DMC will be un-blinded in its assessment of safety and efficacy data.
During the Closed Session, the DMC will develop a consensus on its list of recommendations,
including that relating to whether the trial should continue.
Open and Closed Reports
For each DMC meeting, Open and Closed Reports will be provided (see Section 8 for outlines of the
proposed content of these reports). Open Reports, available to all who attend the DMC meeting, will
include data on recruitment and baseline characteristics, and pooled data on eligibility violations,
completeness of follow-up and compliance. The statisticians will prepare these Open Reports.
Closed Reports, available only to those attending the Closed Sessions of the DMC meeting, will
include confidential information on the primary and secondary endpoints and reporting of SAEs and
AEs.
The Open and Closed Reports should provide information that is accurate, with follow-up that is
complete to within two months of the date of the DMC meeting. The reports should be provided to
DMC members approximately one week prior to the date of the meeting.
Minutes of the DMC meeting
The trial statistician will usually provide minutes of the meetings which should be circulated among
DMC members and agreed. Two sets will be prepared: the Open Minutes and the Closed Minutes.
The Open Minutes will describe the proceedings in the Open Session of the DMC meeting, and will
summarise all recommendations by the DMC. Since these minutes will be circulated immediately to
the sponsor, funding body and to lead trial investigators (as agreed at the initial DMC meeting), it is
necessary that these minutes do not un-blind the efficacy and safety data if the DMC is not
recommending early termination.
The Closed Minutes will describe the proceedings from all sessions of the DMC meeting, including
the listing of recommendations by the Committee. Because it is likely that these minutes will contain
un-blinded information, it is important that they are not made available to anyone outside the DMC.
<<Name>> Data Monitoring Committee (DMC) charter
7
Version 1.0, 5 October 2013
Rather, copies will be kept by the DMC members and also by the statistician preparing the reports,
for archiving at the time of trial closure.
The sponsor will provide a complete collection of Open and Closed Minutes to regulatory authorities
at the time of new drug applications and biologic licensing applications, if applicable.
Recommendations to the Trial Steering Committee (TSC)
At each meeting of the DMC during the conduct of the trial, the DMC will make a recommendation
to the TSC to continue or to terminate the trial. This recommendation will be based primarily on
safety and efficacy considerations and will be guided by statistical monitoring guidelines defined in
this Charter.
The TSC is jointly responsible with the DMC for safeguarding the interests of participating patients
and for the conduct of the trial. Recommendations to amend the protocol or conduct of the trial
made by the DMC will be considered and accepted or rejected by the TSC. The TSC will be
responsible for deciding whether to continue or stop the trial based on the DMC recommendations.
The DMC will be notified of all changes to the protocol or to trial conduct. The DMC concurrence will
be sought on all substantive recommendations or changes to the protocol or trial conduct.
The TSC may communicate information in the Open Report to the sponsor and/or funding body and
may inform them of the DMC recommendations to trial conduct or early trial termination in
instances in which the TSC has reached a final decision agreeing with the recommendation. The TSC
will maintain confidentiality of all information it receives other than that contained in the Open
Reports until after the trial is completed, or until a decision for early termination has been made.
7. STATISTICAL MONITORING GUIDELINES
The main criterion for early stopping of the trial by the TSC upon suggestions from the DMC will be
that evidence from the trial and from other sources suggests a) proof beyond all reasonable doubt
that for all, or for some types of patient, one treatment regimen is clearly indicated or contraindicated, and b) evidence that might reasonably be expected to influence routine clinical practice.
<<Name>> Data Monitoring Committee (DMC) charter
8
Version 1.0, 5 October 2013
The DMC will, however, reserve the right to release any data on outcome or side-effects to the TSC if
it determines at any stage that the combined evidence from this and other trials justifies it.
8. CONTENT OF THE DMC’S OPEN AND CLOSED REPORTS
Open Statistical Report: An Outline














One page outline of the trial design, possibly with a schema
Statistical commentary explaining issues presented in the Open Report figures and tables
DMC monitoring plan and summary of Open Report data presented at prior meetings
Major protocol changes
Information on patient screening
Trial accrual by time and by institution
Eligibility violations
Baseline characteristics (pooled by treatment regimen)
o Demographics
o Laboratory values and other measurements
o Previous treatment usage and other similar information
Days between randomisation and start of treatment
Adherence to medication/treatment schedule (pooled by treatment regimen)
Attendance at scheduled visits (pooled by treatment regimen)
Reporting delays for key events (pooled by treatment regimen)
Length of follow-up data available (pooled by treatment regimen)
Participant treatment and trial status (pooled by treatment regimen)
Closed Statistical Report: An Outline








Detailed statistical commentary explaining issues raised by Closed Report figures and tables
(by coded treatment group, with codes sent to DMC members by a separate mailing)
DMC monitoring plan and summary of Closed Report data presented at prior meetings
Repeat of the Open Report information, in greater detail by treatment group
Analysis of primary and secondary efficacy endpoints
Subgroup analyses and analyses adjusted for baseline characteristics
Analysis of adverse events and overall safety data
Analyses of lab values, including basic summaries and longitudinal analyses
Discontinuation of medications/treatments
9. REFERENCE DOCUMENTS
<<Name>> Protocol Version x.x, date: dd/mmm/yyyy
<<Name>> Data Monitoring Committee (DMC) charter
9
Version 1.0, 5 October 2013
DMC Charter Signature Page
I confirm that I have read this Charter, I understand it, and I will work according to it. I will
also work consistently with the ethical principles that have their origin in the Declaration of
Helsinki and that are consistent with good clinical practice guidelines and applicable laws
and regulations.
DMC Members’ Disclosure Agreement:
I hereby ensure that I do not have a financial interest in the trial outcome and do not have equity or
other competing interests in companies related to the trial. Conflicts which develop during the
conduct of the trial, or during the dissemination of results, will be disclosed.
Confidentiality Agreement:
I hereby ensure that all information made available to me will be treated in strict confidence.
Information that is supplied to facilitate scientific discussions and decisions concerning the
development of the trial will not be reported outside the framework for which the information has
been provided.
Instructions to the DMC member: Please SIGN and DATE two copies of this signature page and PRINT
your name and title on both copies. Keep one copy for your records and return the other completed
copy to:
<<Name>>
Trial Coordinator <<Trial Name>>
Warwick Clinical Trials Unit, Division of Health Sciences,
The University of Warwick, Coventry, CV4 7AL,
United Kingdom
Fax: +44 (0)24 7615 1586
______________________________
____
___ / ____ / ____
Signature of Committee Member
DD / MMM / YYYY
__________________________________
___________________________
Committee Member Name (print or type)
Committee Member Title
_________________________________
___________________________
Name of Institution
Location of Institution (City, Country)
<<Name>> Data Monitoring Committee (DMC) charter
10
Version 1.0, 5 October 2013