Bayesian Two-Stage Adaptive Design in Bioequivalence.

Bioequivalence (BE) studies are an integral component of new drug development process, and play an important role in approval and marketing of generic drug products. However, existing design and evaluation methods are basically under the framework of frequentist theory, while few implements Bayesian ideas. Based on the bioequivalence predictive probability model and sample re-estimation strategy, we propose a new Bayesian two-stage adaptive design and explore its application in bioequivalence testing. The new design differs from existing two-stage design (such as Potvin's method B, C) in the following aspects. First, it not only incorporates historical information and expert information, but further combines experimental data flexibly to aid decision-making. Secondly, its sample re-estimation strategy is based on the ratio of the information in interim analysis to total information, which is simpler in calculation than the Potvin's method. Simulation results manifested that the two-stage design can be combined with various stop boundary functions, and the results are different. Moreover, the proposed method saves sample size compared to the Potvin's method under the conditions that type I error rate is below 0.05 and statistical power reaches 80 %.