Innovative Designs
ADWG KOL Presentation
ADWG KOL Presentation
Friday 11th March, 2011
Caroline Morgan has been invited by the ADWG KOL Presentation team to present recent joint work with Stephane Heritier and Serigne Lô on 11th March 2011.
A related paper is currently in press for the Statistics in Medicine journal.
The work has been motivated by an ongoing international adaptive confirmatory trial. At the interim analysis of this two-stage trial, none, one or two active treatment regimens are selected for further study in the second stage. A combination test approach is used in this practical setting with an extension of the theory to unbalanced randomisation.
The presentation shows that a combination test with suitable weights can still preserve the overall Type I error rate provided that the test statistic is chosen appropriately and the unpooled Z-test for proportions is not used. The accuracy of stagewise p-values is also discussed in a more general framework.
Monte Carlo simulations confirm the validity of the approach retained and evaluate the necessary sample size.
Additional issues addressed during the design of the trial are also examined such as multiplicity due to testing hypotheses on key secondary endpoints, a non-inferiority comparison to an active treatment and covariate adjusted analyses for various types of outcome.
