Independent Data Monitoring Committee for clinical trials

November 23, 2021

Independent Data Monitoring Committee for clinical trials

IDMC – Independent Data Monitoring Committee for clinical trials

An OVERVIEW: What, How, Why, Purpose, Roles, Responsibilities, and Composition of IDMC

The IDMC undergo different names like

• Data & Safety Monitoring Boards (DSMB)

• Data Monitoring Committee (DMC)

• Data Review Board (DRB)

WHAT is an Independent Data Monitoring Committee [IDMC] or [DSMB] or [DMC] or [DRB]?

Clinical trials should be done in accordance with the proper rights, safety, and well-being of human subjects. The sponsor must establish a committee to assess at the intervals the progress of the clinical trial, the critical efficacy endpoints, the safety, and advice the sponsor whether to continue, modify or stop a trial.

The FDA, in 2006 guidance document defines a DSMB or DMC as a group of individuals with pertinent scientific expertise that reviews an ongoing clinical trial, advises the sponsor regarding the safety, quality, continuation or termination of the trial.

IDMC act as the advisory role, not an executive role. It is only the sponsor, who can decide whether to accept or ignore the suggestions of the IDMC and it allows the sponsor to make decisions without bias.

HOW this came into force, the history of IDMCs?

In 1960, the National Institutes of Health (NIH) started sponsoring multi-center trials. Dr. Bernard Greenberg was asked to develop an advisory document regarding the organization and conduct of large, multi-center trials of new treatment interventions. That report was named after the Greenberg Report, was issued in 1967, and then published in 1988.

The Greenberg Report suggested having an independent group of experts for advice about the conduct of the trial. This report was first used in Coronary Drug Project

Dr.Bernard Greenberg

• In 1980, the pharmaceutical industry began forming such groups and the first trial was Cimetidine Stress Ulcer to use IDMC.

• In 1990, the pharmaceutical industry and NIH has increased collaboration resulted in the industry having more contact with researchers who were familiar with IDMCs and strong proponents of their use

• In 1994s, it was recommended in every clinical trial even for any little harm to participants.

• In 1998s, it is made that IDMCs is required for multi-site clinical trials involving any risk to participants.

• In 2001, the sponsors started including the Independent Monitoring Committee (IDMC) to assess the progress of the study as it was recommended by the Indian Good Clinical Practice (GCP).

HOW IDMCs are created?

• IDMCs are created later on before the randomization of the first subject in the trial.

• This committee is selected by the sponsor soon after the investigator is selected.

• This committee is formed according to the documented procedures found in the sponsors Standard Operating Procedures (SOPs)

WHY IDMCs?

The independence of the IDMC is one reason to modify the sharing of important comparative information and to save lots of the integrity in the clinical test from adverse impact resulting from access to trial information.

PURPOSE OF IDMCs?

• The IDMC or DSMB can play a vital role in protecting participant safety.

• Protecting the credibility and integrity of the trial for future subjects.

• Confirming the appropriate conclusion of a trial so that its results can be disseminated.

• Identify the protocol violations that suggest clarification or changes to the protocol are needed.

• Identify unexpectedly high dropout rates that threaten the trial`s ability to supply credible results.

• Ensure the validity of the study results.

Some types of clinical studies require safety monitoring:

• Controlled studies.

• Randomized controlled studies.

• Early studies of the high-risk intervention.

• Clinical studies in the early phases of a novel intervention.

• Complex designs.

• Studies that justify its early termination.

• Studies are carried out in emergency situations.

• Studies that involve vulnerable populations.

ROLES & RESPONSIBILITIES of DSMBs

• Performing interim monitoring like,

✓ Effectiveness.

✓ Safety.

✓ Study conduct.

✓ Consideration of external data.

✓ Studies of less serious outcomes.

• Provide an advisory review of the study protocol and study procedures.

• Providing suggestions to identify problems.

• Sponsor may also request to conduct emergency reviews of data to assess safety-related issues

• Other responsibilities like making Recommendations and maintaining meeting records.

“Charter” is going to be approved by both the IDMC and therefore the trial sponsor before data has been collected. It acts as a link between both the sponsors and the IDMC. It should be carefully documented and accepted.

The charter should include

• Membership composition.

• Responsibilities of the members involved.

• Safety monitoring and analysis plan.

• Conflict of interest (COI) assessment procedure.

• Efficacy data monitoring plan.

• Publication.

• Confidentiality and communication procedures.

COMPOSITION OF IDMC

• Clinicians.

• At least one biostatistician.

• A medical ethicist with knowledge about the design, conduct, and interpretation of trials.