Frequentist 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 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.
Emerson
Scott S
SS
Department of Biostatistics, Box 357232, University of Washington, Seattle, WA 98195, USA. semerson@u.washington.edu
Kittelson
John M
JM
Gillen
Daniel L
DL
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