UCB Japan Co., Ltd., Shinjuku-ku, Japan.
UCB S.A., Brussels, Belgium.
Ther Innov Regul Sci. 2024 Sep;58(5):863-881. doi: 10.1007/s43441-024-00664-z. Epub 2024 May 24.
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.
在日本现行的生物等效性指导原则下，必须使用单一关键研究来建立生物等效性。资源有限的临床试验通常预先规定了最大允许参与者人数。在本文中，我们考虑了一种试验设计，该设计允许在中期分析中进行生物等效性评估，其中总参与者人数考虑到了资源限制。然后，中期分析中可用的选择是分组序贯设计和适应性设计，迄今为止，尚未对两种方法在相同最大参与者数量下的性能进行比较。因此，我们通过进行模拟研究来检查应该使用哪种方法。由于预计在中期分析中可以达到生物等效性，因此使用 Pocock 型α花费函数的研究设计是可取的。使用 Pocock 型α花费函数的模拟结果表明，分组序贯设计和适应性设计之间的性能相似。因此，由于统计和操作复杂性，在日本进行生物等效性研究时，最好选择分组序贯设计。
