title: Modifications of sequential designs in bioequivalence trials.
abstract: Bioequivalence (BE) studies are designed to show that two formulations of one drug are equivalent and they play an important role in drug development. When in a design stage, it is possible that there is a high degree of uncertainty on variability of the formulations and the actual performance of the test versus reference formulation. Therefore, an interim look may be desirable to stop the study if there is no chance of claiming BE at the end (futility), or claim BE if evidence is sufficient (efficacy), or adjust the sample size. Sequential design approaches specially for BE studies have been proposed previously in publications. We applied modification to the existing methods focusing on simplified multiplicity adjustment and futility stopping. We name our method modified sequential design for BE studies (MSDBE). Simulation results demonstrate comparable performance between MSDBE and the original published methods while MSDBE offers more transparency and better applicability. The R package MSDBE is available at https://sites.google.com/site/modsdbe/.
authors: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, USA.
authors: Cheng
authors: C
authors: Zheng
authors: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, USA.
authors: Lihui
authors: L
authors: Zhao
authors: Celgene International, Boudry, Switzerland.
authors: Jixian
authors: J
authors: Wang
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D003627:Data Interpretation, Statistical; D006801:Humans; D012107:Research Design; D018401:Sample Size; D013223:Statistics as Topic; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
keywords: adaptive design; bioequivalence; sample size re-estimation; sequential design