title: Group-sequential methods for adaptive seamless phase II/III clinical trials.
abstract: The last 10 years have seen considerable interest in clinical trial designs that allow the seamless combination of Phases II and III in a single clinical trial. Such designs bring together the selection of the most promising of a number of treatments, as usually performed in a Phase II clinical trial, with the rigorous analysis and control of type I error rates required for a Phase III clinical trial. Statistically, the challenge is that of allowing for multiple comparisons arising both from repeated analyses of the accumulating data and from selection of a treatment on the basis of data that will be included in the final analysis. This challenge can be met in a number of different ways. This paper reviews methods based on the group-sequential methodology for monitoring of sequential clinical trials. The main focus of the paper will be a description of the methodology, including the setting in which short-term data are used for decision making at an early interim analysis.
authors.affiliation: Warwick Medical School, The University of Warwick, Coventry, United Kingdom. n.stallard@warwick.ac.uk
authors.forename: Nigel
authors.initials: N
authors.lastname: Stallard
mesh_terms: D017322:Clinical Trials, Phase II as Topic / Q000379:methods* / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000379:methods* / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D057239:Early Termination of Clinical Trials; D023381:Endpoint Determination; D015233:Models, Statistical; D012107:Research Design / Q000706:statistics & numerical data*; D018401:Sample Size; D016896:Treatment Outcome