Frequentist evaluation of group sequential clinical trial designs

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Abstract

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 these 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 frequentist operating characteristics of a particular stopping rule might be evaluated to ensure that the selected clinical trial design satisfies the constraints imposed by the many different disciplines represented by the clinical trial collaborators. Copyright © 2007 John Wiley & Sons, Ltd.

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