Performance Evaluation of Interim Analysis in Bioequivalence Studies

• Published in: Therapeutic innovation & regulatory science Vol. 58; no. 5; pp. 863 - 881
• Main Authors: Isogawa, Naoki, Grieve, Andy, Ishii, Ryota, Maruo, Kazushi
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2024; Springer Nature B.V
• Subjects: Bioequivalence; Clinical trials; Clinical Trials as Topic; Computer Simulation; Design analysis; Drug Safety and Pharmacovigilance; Group dynamics; Humans; Japan; Medicine; Original Research; Performance evaluation; Pharmacotherapy; Pharmacy; Research Design; Therapeutic Equivalency; Japan; Group sequential design; Adaptive design; Japan guideline for bioequivalence study
• ISSN: 2168-4790; 2168-4804; 2168-4804
• DOI: 10.1007/s43441-024-00664-z

Under current bioequivalence guidelines in Japan, it is mandatory to establish bioequivalence using a single pivotal study. Clinical trials with limited resources usually have a pre-defined maximum permissible number of participants. In this manuscript, we considered a trial design that would allow for bioequivalence evaluation at an interim analysis in which the total number of participants takes into account the resource constraints. Then, available options at the interim analysis are group sequential designs and adaptive designs, A comparison of the performance of the two methods under same maximum participant number has not been conducted thus far. So we examined which method should be used by conducting a simulation study. Since bioequivalence is expected to be achieved at the interim analysis, a study design using a Pocock-type alpha spending function is preferrable. Simulation results using a Pocock-type alpha spending function showed similar performance between group sequential and adaptive designs. Consequently, due to statistical and operational complexity, it is preferable to choose group sequential designs for bioequivalence study in Japan.