title: Two-stage designs for cross-over bioequivalence trials.
abstract: The topic of applying two-stage designs in the field of bioequivalence studies has recently gained attention in the literature and in regulatory guidelines. While there exists some methodological research on the application of group sequential designs in bioequivalence studies, implementation of adaptive approaches has focused up to now on superiority and non-inferiority trials. Especially, no comparison of the features and performance characteristics of these designs has been performed, and therefore, the question of which design to employ in this setting remains open. In this paper, we discuss and compare 'classical' group sequential designs and three types of adaptive designs that offer the option of mid-course sample size recalculation. A comprehensive simulation study demonstrates that group sequential designs can be identified, which show power characteristics that are similar to those of the adaptive designs but require a lower average sample size. The methods are illustrated with a real bioequivalence study example.
authors: Institute of Medical Biometry and Informatics, University of Heidelberg, D-69120 Heidelberg, Germany.
authors: Meinhard
authors: M
authors: Kieser
authors: Institute of Medical Biometry and Informatics, University of Heidelberg, D-69120 Heidelberg, Germany.
authors: Geraldine
authors: http://orcid.org/0000-0002-2451-1660
authors: G
authors: Rauch
mesh_terms: D056808:Biostatistics / Q000379:methods; D003198:Computer Simulation; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D006801:Humans; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design / Q000706:statistics & numerical data; D018401:Sample Size; D013806:Theophylline / Q000008:administration & dosage; D013810:Therapeutic Equivalency
chemical_list: D003692:Delayed-Action Preparations; D013806:Theophylline
keywords: adaptive design; bioequivalence; cross-over design; sample size recalculation; two-stage design