Statistical methods for monitoring clinical trials.

Clinical trials are monitored to determine whether a treatment is safe and effective. If it becomes clear that treatment is superior to control, ethical considerations compel us to stop the study and make the treatment available to control patients. On the other hand, if it becomes clear that the treatment will not be shown superior to control, we would like to stop the study and save valuable resources for more promising agents. But how much evidence is enough to declare benefit, and what criteria do we use to stop for lack of benefit? This article reviews monitoring procedures designed to answer these two questions. The B-value approach of Lan and Wittes (1) and Lan and Zucker (2) is used to unify the monitoring of many different kinds of trials, including those with continuous, dichotomous, or survival outcomes.