Interim analyses and sequential designs in phase III studies

Recruitment of patients to a clinical trial usually occurs over a period of time, resulting in the steady accumulation of data throughout the trial's duration. Yet, according to traditional statistical methods, the sample siz e of the trial should be determined in advance, and data collected on all s ubjects before analysis proceeds. For ethical and economic reasons, the tec hnique of sequential testing has been developed to enable the examination o f data at a serees of interim analyses. The aim is to stop recruitment to t he study as soon as there is sufficient evidence to reach a firm conclusion . In this paper we present the advantages and disadvantages of conducting i nterim analyses in phase III clinical trials, together with the key steps t o enable the successful implIementation of sequential methods in this setti ng. Examples are given of completed trials, which have been carried out seq uentially, and references to relevant literature and software are provided.