The primary responsibility of the Data Monitoring Committee (DMC) throughout the duration of a trial is to ensure the benefit to the patient outweighs any potential risk. CROS NT’s biostatistics team looks at the challenges of ongoing analysis for a DMC.
The DMC generally carries out the following activities:
- Periodic review and evaluation of accumulated study data related to safety, study conduct and progress, efficacy, scientific validity and integrity
- Recommendations concerning the continuation, modification or termination of a trial
- Maintaining confidentiality when it comes to DMC internal discussions and the contents of any reports
Confidentiality is always one of the main problems the members of the DMC face when releasing results or interim analysis.
How can confidentiality be preserved in a DMC?
- Study groups can be masked for DMC review, for example X vs. Y instead of experimental vs. control. However, the key to the grouping code must be available for immediate unmasking if necessary.
- DMC meeting format that includes both open and closed sessions has proven useful. Open sessions allow for interaction and discussion of study logistical matters between the IDMC and Investigator representatives as well as the Sponsor and the data management and biostatistics teams (and also regulatory authorities if necessary). Meanwhile, closed sessions are restricted to IDMC voting members and statisticians only, and data from the treatment group is presented and discussed followed by recommendations and follow up actions.
- DMC operating procedures should be defined in the beginning of the trial to describe how the DMC works and communicates with study participants. The DMC should also discuss the administrative and methodological aspects of their work and the flow of data.
- Any conflicts of interest among DMC members should be discussed prior to starting the trial
According to FDA guidelines, “the integrity of a trial is best protected when the statistician preparing unblinded data for the DMC is external to the Sponsor”. Independent statisticians are therefore beneficial in order to keep trial participants “blinded” and maintain objectivity for the statistical team.
An alternative approach being implemented lately is to use an Independent Scientific Advisory Committee (ISAC) and/or different CROs to manage blinded and unblinded data and separate CRFs and databases.
What are the responsibilities of the ISAC?
- Act as a critical link between the IDMC and the Clinical Trial team and/or Sponsor
- Produce interim data analysis and reports for the IDMC
- Protocol development, support and revision especially with regards to study design and analysis
- Statistical guidance for interim monitoring
- Verification of key data items
- Identification of topics of concern to the IDMC
- Support for the preparation of final analyses and publications
There are several ways the ISAC can support the confidentiality of DMCs. The ISAC facilitates the work of the IDMC and the interactions between the IDMC and the Sponsor and steering committee. They also support with producing interim monitoring reports.
An Independent Statistical Analysis Center can be responsible for a broad range of activities that support the IDMC while maintaining good clinical trial conduct and the essential features of a well-established clinical trial model outlined in regulatory guidelines (such as FDA, EMA and NIH).
Having an independent statistical team for IDMCs is favored by regulatory authorities it is an effective and efficient method for ensuring confidentiality.
CROS NT has a team of statistical consultants across Europe and the United States with extensive experience in protocol design and statistical methodology as well as providing support for DMCs and regulatory authority meetings. Their experience spans over 40 therapeutic areas, over 100 indications, Phase I-IV drug studies and medical device studies. To request information, contact us.