Statistical and ethical issues in monitoring clinical trials

Most randomized clinical trials require periodic monitoring of the accumulating data. While the efficiency of trial management is enhanced by data monitoring, ethical reasons should primarily dictate the need to terminate or change a trial in response to interim findings. This article focuses on the ethical dilemma of when to stop a clinical trial and places statistical stopping rules in the context of such ethical decision making. Other issues include the organization of data monitoring committees and the problems of premature publication and exaggerated estimation in trials that stop early. Several topical examples are used to convey the relevance of these issues to current practice.