Statistical Assessment of Biosimilarity Based on the Relative Distance Between Follow-on Biologics for Time-to-Event Endpoints

The two-arm parallel design that is commonly used to assess biosimilarity has the drawback that it does not take into account the inherent variability within the reference products. The three-arm parallel design was proposed to solve this problem. The purpose of this article was to extend the previous results to the time-to-event endpoints in the exponential model, the Cox proportional hazard model, and the restricted mean survival time. The relative distance is defined, and the corresponding test procedures are developed based on asymptotic theory. The Type I error rates and powers are investigated theoretically and empirically. Supplementary materials for this article are available online.

常用于评估生物类似药相似性的双臂平行设计（two-arm parallel design）存在一项固有缺陷：未考虑参比制剂的内在变异性。针对该问题，研究人员提出了三臂平行设计（three-arm parallel design）。本文旨在将既往研究结论推广至指数模型（exponential model）、Cox比例风险模型（Cox proportional hazard model）及限制性平均生存时间（restricted mean survival time）框架下的事件发生时间终点场景中。文中定义了相对距离（relative distance），并基于渐近理论（asymptotic theory）构建了对应的检验流程。研究通过理论与实证相结合的方式，对一类错误率（Type I error rates）与检验效能进行了考察。本文的补充材料可在线获取。