Lu Qingshu, Tse Siu-Keung, Chow Shein-Chung, Lin Min
Singapore Clinical Research Institute, Singapore.
J Biopharm Stat. 2012;22(4):773-84. doi: 10.1080/10543406.2012.678528.
In the pharmaceutical industry, a two-stage seamless adaptive design that combines two separate independent clinical trials into a single clinical study is commonly employed in clinical research and development. In practice, in the interest of shortening the development process, it is not uncommon to consider study endpoints with different treatment durations at different stages (Chow and Chang, 2006 ; Maca et al., 2006 ). In this study, our attention is placed on the case where the study endpoints of interest are time-to-event data where the durations at the two stages are different with nonuniform patient entry and losses to follow-up or dropouts. Test statistics for the final analysis based on the combined data are developed under various hypotheses for testing equality, superiority, noninferiority, and equivalence. In addition, formulas for sample size calculation and allocation between the two stages based on the proposed test statistic are derived.
在制药行业，一种将两个独立的临床试验合并为一项临床研究的两阶段无缝自适应设计常用于临床研究与开发。实际上，为了缩短研发过程，在不同阶段考虑具有不同治疗时长的研究终点是很常见的（周和张，2006；马卡等人，2006）。在本研究中，我们关注的情况是，感兴趣的研究终点是事件发生时间数据，其中两个阶段的时长不同，患者入组不均匀且存在失访或退出情况。基于合并数据进行最终分析的检验统计量是在各种用于检验相等性、优越性、非劣效性和等效性的假设下开发的。此外，还推导了基于所提出的检验统计量的样本量计算和两阶段之间分配的公式。
