Statistics Seminar: Nigel Stallard

Nigel Stallard, University of Warwick

Friday 13 December 2013, 1400-1500
A54, Postgraduate Statistics Centre Lecture Theatre

Using early outcome data for decision making in seamless phase II/III clinical trials

Most statistical methodology for confirmatory phase III clinical trials focuses on the comparison of a control treatment with a single experimental treatment, with selection of this experimental treatment made in an earlier exploratory phase II trial. Recently, however, there has been increasing interest in methods for adaptive seamless phase II/III trials that combine the treatment selection element of a phase II clinical trial with the definitive analysis usually associated with phase III clinical trials.

A number of methods have been proposed for the analysis of such trials to address the statistical challenge of ensuring control of the type I error rate. These methods rely on the independence of the test statistics used in the different stages of the trial.

In some settings the primary endpoint can be observed only after long-term follow-up, so that at the time of the first interim analysis primary endpoint data are available for only a relatively small proportion of the patients randomised. In this case if short-term endpoint data are available, these could be used along with the long-term data to inform treatment selection. The use of such data breaks the assumption of independence underlying existing analysis methods.

This talk presents new methods that allow for the use of short-term data. The new methods control the overall type I error rate, either when the treatment selection rule is pre-specified, or when it can be fully flexible, but gain in power from the use of the short-term endpoint data when the short and long-term endpoints are correlated.