Evaluation of Group Sequential Clinical Trial Designs

Group sequential stopping rules are often used as guidelines in the monitoring of clinical trials in order to address the ethical and efficiency issues inherent in human testing of a new treatment or preventive agent for disease. Such stopping rules have been proposed based on a variety of different criteria, both scientific (e.g., estimates of treatment effect) and statistical (e.g., frequentist type I error, Bayesian posterior probabilities, stochastic curtailment). It is easily shown, however, that a stopping rule based on one of those criteria induces a stopping rule on all other criteria. Thus the basis used to initially define a stopping rule is relatively unimportant so long as the operating characteristics of the stopping rule are fully investigated. In this paper we describe how the operating characteristics of a particular stopping rule might be evaluated in order to ensure that the selected clinical trial design satisfies the constraints imposed by the many different disciplines represented by the clinical trial collaborators. In particular, we present concise methods of presenting Bayesian operating characteristics over a range of prior distributions and discuss the difficulty interpreting measures based on stochastic curtailment.