Clinical Trial Data and Safety Monitoring Boards

Abstract

Controlled clinical trials are a cornerstone in the search for medical therapeutic advances. Since the introduction of this concept, there has been substantial progress in the design, conduct, and analysis of such studies, and many have become quite complex. A growing awareness of ethical issues emerging from such trials has led to increased public scrutiny and dialogue between patients, investigators, institutions, and funding agencies. The recent broader role of industrial/financial sponsorship of such endeavors has led to new issues and challenges for all interested parties. The Data and Safety Monitoring Board (DSMB) is now considered a critical component of the administration and conduct of large multicenter clinical trials. Early cessation of large trials because of major advantages or untoward effects of the treatment under study has recently underscored the pivotal internal peer review role of the DSMB. Although the general need for treatment monitoring has been recognized by the National Institutes of Health since at least 1979, surprisingly little information exists concerning terms of reference, authority, composition, and operating procedures by which such groups function.1 It is the purpose of this essay to explore these issues further, with the intent of fostering a constructive dialogue and framework from which to construct DSMB guidelines. Those charged with the responsibility of designing, leading, conducting, and sponsoring clinical trials must give special care to the structure and role of the DSMB.2 It should provide informed and independent advice to the principal investigator, steering committee, and sponsor. For the purposes of this discussion, the principal investigator of a trial will be presumed to be the chairman of the steering committee, and the word “sponsor” will refer to either a peer-reviewed funding agency or an industrial source. A DSMB chairman should be appointed jointly by the steering committee and the sponsor: this individual …