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 size of the trial should be determined in advance, and data collected on all subjects before analysis proceeds. For ethical and economic reasons, the technique of sequential testing has been developed to enable the examination of data at a series of interim analyses. The aim is to stop recruitment to the study as soon as there is sufficient evidence to reach a firm conclusion. In this paper we present the advantages and disadvantages of conducting interim analyses in phase III clinical trials, together with the key steps to enable the successful implementation of sequential methods in this setting. Examples are given of completed trials, which have been carried out sequentially, and references to relevant literature and software are provided.
Todd
S
S
Medical and Pharmaceutical Statistics Research Unit, The University of Reading, PO Box 240, Earley Gate, Reading, Berkshire, RG6 6FN. s.c.todd@reading.ac.uk
Whitehead
A
A
Stallard
N
N
Whitehead
J
J
D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D006801:Humans; D008432:Mathematical Computing; D018579:Patient Selection; D012107:Research Design / Q000592:standards*