Inside the Mind of the DMC: A Review of Principles and Issues with Case Studies

Abstract

A data monitoring committee (DMC) can have an extremely challenging job. Stop a trial too soon, and results are inconclusive and the trial fails to obtain answers to important questions that could inform future clinical practice. Stop a trial too late, and trial participants are exposed to potentially harmful or ineffective interventions longer than necessary. Securing convincing and conclusive evidence and the ethical responsibility to current and future patients are weighed carefully during DMC deliberations. The ability to interpret complex information, and appreciation of issues affecting scientific integrity, are critical for the DMC to protect trial participants and public trust. Challenges faced by and issues of prudence faced by DMCs are discussed including interim analysis issues, assessing the totality of information with statistical boundaries as guidelines, interpretation of composite and surrogate outcomes, reactions to early trends, benefit:risk assessment, landscape changes, subgroup analyses, composing information for a comprehensive understanding of patient-centric effects, and evaluating the value of additional data. Case studies illustrate how DMCs addressed the challenges.

Keywords: Benefit:risk; Composite endpoints; Confidentiality; DMC; DSMB; Independence.