INTERIM ANALYSES AND STOPPING RULES IN CANCER CLINICAL-TRIALS

A clinical trial conducted according to a schedule of interim analyses written into the protocol, and stopped according to a predetermined r ule, is known to statisticians as a sequential clinical trial. This me thodology is becoming more widely used in trials concerning life-threa tening diseases because of its ability to adjust the sample size to th e emerging information on treatment efficacy. When treatments under co mparison differ appreciably, small samples will be sufficient; for mor e subtle differences larger numbers of patients need to be recruited. Sequential methods have already been used in certain cancer clinical t rials, and they are especially appropriate for such studies. In this p aper the principles of sample size determination are reviewed, and the essential aspects of designing sequential trials are described. The n ecessity for a special form of statistical analysis following a sequen tial trial is explained. and the consequences of early or late stoppin g on the analysis are investigated. Compromises which have to be made between the formal requirements of theory and the practical realities of trial conduct are discussed.