Sample Size Determination for Three-Arm Equivalence Trials with Survival Outcomes(2/2)

The assessment of equivalence in a clinical trial may be conducted through a three-arm trial (test drug, reference drug, and placebo). The three-arm equivalence trial consists of three hypothesis tests in practice, where two hypothesis tests are demonstrating the superiority of test drug and reference drug against placebo, and the other one is demonstrating the equivalence of test drug and reference drug. In the literature, so far, the sample size determination for three-arm design with survival endpoints is limited. Therefore, to complement the literature, the purpose of this study is to develop a statistical method to calculate the sample size for three-arm equivalence trials with censored survival outcome as the primary endpoint. General classes of parametric distributions will be considered to calculate the sample size. Moreover, treating the three groups as covariates, the semi-parametric hazards regression model can be employed to the three-arm testing procedure. The non-proportionality hazards regression models including the AFT and extended hazards models will be applied to the sample size determination. We illustrate the use of the method by considering a randomized, active- and placebo-controlled trial in subjects with travelers’ diarrhea. The validity of the proposed method will be investigated by simulation studies.