CURRENT ISSUES REGARDING DATA AND SAFETY MONITORING COMMITTEES IN CLINICAL TRIALS

Last week, I attended the 10th Annual Conference on Statistical Issues in Clinical Trials held in the camps of the University of Pennsylvania. This year, the topic is about "Current Issues Regarding Data and Safety Monitoring Committees in Clinical Trials".

The conference is supposed to discuss the current issues and emerging challenges in the practice of data monitoring committees, however, these issues and challenges discussed are not new. These issues are known for a long time and remain as issues.

One thing I like this one-day annual conference is that all presentation slides including the panel discussions are posted online. For DMC discussions this year, the presentation slides are available at www.cceb.med.upenn.edu/events/10th-annual-conference-statistical-issues-clinical-trials

The early days, the term DSMB (data and safety monitoring board) was used. After FDA issued its guidance "The Establishment and Operation of Clinical Trial Data Monitoring Committees for Clinical Trial Sponsors", the term DMC (data monitoring committee) become popular. In the conference this year, a new term DSMC (data and safety monitoring committee) is also used.

There are several talks about the training for DMC members and the need to train more people who can serve on the data monitoring committee. I felt that the discussion about the training for DMC members is targeting the wrong audience. Instead of targeting the statisticians, the focus should be on those MDs in the medical field. Very often, we have difficulties to find the MDs who can serve on the data monitoring committee, let alone to find the MDs who have prior experience serving in the data monitoring committee. For a large scale clinical trial, there may be several committees: steering committee, event or endpoint adjudication committee, and data monitoring committee. There is often a shortage of members for these committees. 

Nowadays, the study protocols are getting more and more complicated. The DMC committee members may not understand the complexity of the complicated trial design.  This is especially true for clinical trials using adaptive design and Bayesian design. This poses challenges to the DMC members.

We used to debate whether or not the data monitoring committee should be given the semi-unblinded materials for review where the treatment group is designated as "X" or "Y" instead of the true treatment assignment. The conference presentations said loudly that DMC should have sole access to interim results with complete unblinding (not semi-unblinding) on relative efficacy & the relative safety of interventions.

Here are some points from Dr. Fleming’s presentation “DMCs: Promoting Best Practices to Address Emerging Challenges”

Mission of the DMC

• To Safeguard the Interests of the Study Participants
• To Preserve Trial Integrity and Credibility to enable the clinical trial to provide timely and reliable insights to the broader clinical community

 Proposed Best Practices and Operating Principles

• Achieving adequate training/experience in DMC process
• Indemnification
• Addressing confidentiality issues
• Implementing procedures to enhance DMC independence

                DMC meeting format
                Creating an effective DMC Charter
                DMC recommendations through consensus, not by voting
                DMC contracting process

• Defining the role of the Statistical Data Analysis Center
• Better integration of regulatory authorities in DMC process

REFERENCES:

• Fleming TR DeMets DL et al (2017) Data monitoring committees: promoting best practices to address emerging challenges. Clinical Trials
• DeMets DL and Ellenberg SS (2016) Data monitoring committees - expect the unexpected. New England Journal of Medicine
• CTTI (Clinical trials transformation initiative): Data monitoring committees project