A confirmatory seamless phase II/III clinical trial design incorporating short‐term endpoint information

Seamless phase II/III designs allow strong control of the familywise type I error rate when the most promising of a number of experimental treatments is selected at an interim analysis to continue along with the control treatment. If the primary endpoint is observed only after long‐term follow‐up it may be desirable to use correlated short‐term endpoint data available at the interim analysis to inform the treatment selection. If short‐term data are available for some patients for whom the primary endpoint is not available, basing treatment selection on these data may, however, lead to inflation of the type I error rate. This paper proposes a method for the adjustment of the usual group‐sequential boundaries to maintain strong control of the familywise error rate even when short‐term endpoint data are used for the treatment selection at the first interim analysis. This method allows the use of the short‐term data, leading to an increase in power when these data are correlated with the primary endpoint data. Copyright © 2010 John Wiley & Sons, Ltd.