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.
Stallard
Nigel
N
Warwick Medical School, The University of Warwick, Coventry CV4 7AL, U.K. n.stallard@warwick.ac.uk
D056808:Biostatistics; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data*; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D006801:Humans; D015233:Models, Statistical; D012044:Regression Analysis; D018401:Sample Size; D013997:Time Factors