Sample size and power estimation in "thorough" QT/QTc studies with parallel group design.

ABSTRACT

We developed analytical results for computing the power in a thorough QT/QTc study with a four-group parallel design in which the treatments are placebo, positive control, supratherapeutic dose of investigational drug, and therapeutic dose of investigational drug. An assessment of non-inferiority of the supratherapeutic dose to placebo is performed by the intersection-union test within the framework of a linear mixed effects analysis with baseline covariate. The power estimates obtained using analytical results and from the simulation study were presented and they are quite close and hence the analytical results could be used for computing power and sample size in the planning stage of a thorough QT/QTc study.