title: Frequentist evaluation of group sequential clinical trial designs.
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.
authors.affiliation: Department of Biostatistics, Box 357232, University of Washington, Seattle, WA 98195, USA. semerson@u.washington.edu
authors.forename: Scott S
authors.initials: SS
authors.lastname: Emerson
authors.forename: John M
authors.initials: JM
authors.lastname: Kittelson
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Gillen
mesh_terms: D001499:Bayes Theorem; D001699:Biometry / Q000379:methods*; D026661:Clinical Trials Data Monitoring Committees; D023381:Endpoint Determination; D006801:Humans; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000941:ethics / Q000592:standards*; D012107:Research Design / Q000592:standards*; D018401:Sample Size; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration