THE ROLE OF DATA MONITORING IN CLINICAL RESEARCH
Introduction:
A The Data Monitoring Committee is a group of Clinicians and Bio statisticians appointed by sponsors who provide independent assessment of the safety,validity and integrity of clinical trials. In the United States, the FDA requires the formation of DMC in all trials that assess new interventions. In other clinical studies that have safety issues, double-blind treatment studies are expected to have a major effect on clinical practice. In clinical research in psychiatry because they provide protection for vulnerable populations. This describes the role, formation and operation of the DMC
What is a
Data Monitoring Committee?
A data monitoring committee (DMC) is also called as data and safety monitoring board. It is an independent group of experts who monitor patient safety and treatment efficacy data while a clinical trial is ongoing. The committee is responsible for reviewing the data collected during the trial, and making recommendations to the sponsor regarding whether the trial should continue as planned, be modified, or be terminated. The DMC is also responsible for ensuring the safety of the trial participants and protecting the integrity of the trial data.
Need for a
DMC:
Many randomized clinical
trials are double blind- where no one knows what the treatment will be given to
each trial participant. Blinding includes a participant, a doctor or an
organization which is sponsoring the trial. Once the database is finalized,
then the true assignments will be disclosed.
Clinical trials may continue
for many years. The DMC is a group that consists of 3 to 7 members who are
independent of conducting the clinical trial. One member will be a
statistician. Clinicians are well informed about the disease indications and
should be represented , as well as clinicians well informed in the fields of
any suspected safety effects. Ethicists or representatives may be included,
especially for vulnerable populations. The DMC has the power to continue or
termination of the study .
There are three reasons a
DMC might recommend termination of study: safety concerns, outstanding benefits
and futility.
When should
a study include the Data Monitoring Committee?
A study should include a data monitoring committee when it involves a high risk interventions , such as those involving new drugs or medical devices, or when it involves vulnerable populations, such as children or elderly individuals. In addition, a DMC should be included when the study is large and complex, or when the study is conducted in multiple sites. The DMC can provide an independent assessment of the safety and efficacy of the intervention, and can help ensure the integrity of the study data by reviewing intervals. The DMC can also monitor the study for any unexpected AE’s and can make recommendations to the sponsor regarding whether the trial should continue as planned or modified or terminated.
The
Difference in the Responsibilities of DMC and IRB:
The Data Monitoring
Committee (DMC) and institutional review board (IRB) have different
responsibilities in clinical trials. The DMC is responsible for monitoring the
safety and efficacy of the interventions
being studied. The DMC is an independent group of experts who are
responsible for reviewing the data collected during the trial, and making recommendations to the sponsor regarding the
safety and efficacy.
The Institutional Review Board (IRBs) also has the responsibility for monitoring the safety and efficacy of the trial subjects. The sponsors of clinical trials need to submit reports to institution’s IRB listing SAEs that occur in trial subjects. IRBs do not receive outcome data or have statistical expertise to perform interim analysis to know the risks and benefits of the trial.
The
Composition of Data Monitoring Committees:
DMCs typically include independent experts in the relevant fields, such as bio statisticians , clinicians, and other subject matter experts. The DMC may also include patient representatives. Members of the DMC should not be involved in the conduct of studies, and should have no conflicts of interest related to the study. The DMC should be independent of the sponsor and have no financial or other ties to the sponsor. The size of the DMC also varies. There are usually at least three members or there can be more DMC members for large studies .
Operational
aspects of Data Monitoring Committees:
The operational
aspects of data monitoring committees (DMCs) include the following :
l Charter:-
The FDA
recommends that each DMC establish a trial specific charter with clear
operating procedures. The DMC should
have a written charter that outlines its purpose, responsibilities, and
procedures.
It defines the
relationship between the sponsor and the DSMB.
The following
items should be addressed in the charter;
1. Description
2. Objectives
3. Meeting arrangements
4. Data management and security
5. Documentation
l Meetings:-
The DMC should meet at regular intervals. The meetings can be held in person or by teleconference.
|
Open Sessions |
Closed Sessions |
Minutes |
|
Ø Executive Committee Ø DMC Ø No unblinded data is required |
Ø DMC Only Ø Unblinded data should be reviewed |
Ø Document deliberations Ø Confidentiality is the key. |
l Data Review:-
The DMC should review the data in a systematic and objective manner. The DMC should use pre-specified criteria to assess the safety and efficacy of the intervention being studied.
l Reporting:-
The DMC should
provide written reports to the sponsor regarding their findings and
recommendations. The reports should be provided in a timely manner and should
include any recommendations for changes
to the study protocol.
l Confidentiality:-
The DMC should communicate with the sponsor and the study investigators as needed. The DMC should also communicate with IRB as needed
The Role of Statisticians and the Interim analyses
they conduct in DMC:
Independent statisticians who are not involved in
trial management and who are not employed by the trial sponsor should perform
the interim analysis. The statisticians performing the interim analysis are
often the primary statisticians involved in the design and management of the
trial. The statisticians performing the interim analyses, aren’t the primary
statisticians of the trial, they are usually appointed by the sponsors.
Study protocols usually include the description of
interim analyses. To avoid bias, a plan for the time and content of the interim
analyses should have to be finalized before the first analysis of unblinded
results conducted. Interim analyses contain descriptions of when analyses will
be performed based on the rate of information accumulation, on chronological
time, or any other criteria. If appropriate, the interim analyses plan can
contain criteria for stopping the trial prior because of the futility.
DMC’s plays a critical role in ensuring safety and
efficacy of clinical trials. They are responsible for conducting interim
analyses of the study data, monitoring the data for safety concerns. The DMC’s
are composed of independent experts who are knowledgeable in the disease area
being studied, who have no conflicts of
interest with the study sponsor. An appropriately qualified DMC can ensure the
safety of trial subjects and uphold the balance of the trial by continuous
reviewing of safety data. It also helps the validity and integrity of clinical
trial.
References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118004/
https://en.m.wikipedia.org/wiki/Data_monitoring_committee
https://www.slideshare.net/jbarag/the-role-of-data-monitoring-committees
Student Name: Shaik Fameen
Student ID:104/062023
Qualification: B. Pharmacy
e-Mail ID: fameenfayish@gmail.com
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