Biometrics Department, Research Division, Kyowa Kirin Co., Ltd. Otemachi Financial City Grand Cube, 1-9-2 Otemachi, Chiyoda-ku, Tokyo, 100-004, Japan.
Biometrics Department, Development Division, Kyowa Kirin, Inc, Princeton, NJ, USA.
Ther Innov Regul Sci. 2024 Nov;58(6):1129-1137. doi: 10.1007/s43441-024-00692-9. Epub 2024 Aug 23.
During discussions at the Data Science Roundtable meeting in Japan, there were instances where the adoption of the BOIN design was declined, attributed to the extension of study duration and increased sample size in comparison to the 3 + 3 design. We introduce an accelerated BOIN design aimed at completing a clinical phase I trial at a pace comparable to the 3 + 3 design. Additionally, we introduce how we could have applied the BOIN design within our company, which predominantly utilized the 3 + 3 design for most of its clinical oncology dose escalation trials. The accelerated BOIN design is adaptable by using efficiently designated stopping criterion for the existing BOIN framework. Our approach is to terminate the dose escalation study if the number of evaluable patients treated at the current dose reaches 6 and the decision is to stay at the current dose for the next cohort of patients. In addition, for lower dosage levels, considering a cohort size smaller than 3 may be feasible when there are no safety concerns from non-clinical studies. We demonstrate the accelerated BOIN design using a case study and subsequently evaluate the performance of our proposed design through a simulation study. In the simulation study, the average difference in the percentage of correct MTD selection between the accelerated BOIN design and the standard BOIN design was - 2.43%, the average study duration and the average sample size of the accelerated BOIN design was reduced by 14.8 months and 9.22, respectively, compared with the standard BOIN design.
在日本举行的“数据科学圆桌会议”的讨论中，有一些研究采用了 BOIN 设计，而另一些研究则拒绝采用，原因是与 3+3 设计相比，研究持续时间延长且样本量增加。我们提出了一种加速的 BOIN 设计，旨在以与 3+3 设计相当的速度完成临床 I 期试验。此外，我们还介绍了如何在我们的公司中应用 BOIN 设计，我们的公司主要在大多数临床肿瘤剂量递增试验中使用 3+3 设计。加速的 BOIN 设计可以通过使用现有的 BOIN 框架中的有效指定的停止标准来进行调整。我们的方法是，如果当前剂量下接受治疗的可评估患者数量达到 6，并且决定为下一组患者维持当前剂量，则终止剂量递增研究。此外，对于较低的剂量水平，如果非临床研究没有安全问题，则考虑较小的队列大小（小于 3）可能是可行的。我们使用案例研究来展示加速的 BOIN 设计，然后通过模拟研究来评估我们提出的设计的性能。在模拟研究中，加速 BOIN 设计与标准 BOIN 设计之间正确选择 MTD 的百分比的平均差异为-2.43%，与标准 BOIN 设计相比，加速 BOIN 设计的平均研究持续时间和平均样本量分别减少了 14.8 个月和 9.22。
