Selection of Adaptive Designs in Studies of Bioequivalence. Decision Criteria

Adaptive designs can be selected for bioequivalence studies of drugs for which there are no data on the variability of pharmacokinetic parameters (the within-individual variability coefficient, CVintra). These are designs with prospective plans for modification of volunteer sample size based on analysis of the results obtained within the study. The aim of the present work was to analyze the guidelines and protocols for bioequivalence studies with adaptive designs for the validity of selecting such a design for a number of parameters. The results of this retrospective study identified key points and generated a list of shortcomings. The need for a comprehensive literature search for CVintra values is noted - selection of an adaptive design is justified if no such a search is run and/or when there are conflicting data. Decision criteria for the selection of adaptive designs in bioequivalence studies are presented. Examples given will unify the approach and avoid mistakes in planning further bioequivalence studies.