Lu Qingshu, Tse Siu Keung, Chow Shein-Chung
Department of Statistics & Finance, University of Science and Technology of China, Anhui, People's Republic of China.
J Biopharm Stat. 2010 Jul;20(4):705-19. doi: 10.1080/10543401003618066.
In recent years, the use of a two-stage seamless design in clinical trials has attracted much attention. A two-stage seamless trial design is referred to as a study design that combines two separate clinical studies that are normally conducted to achieve separate objectives, such as a phase II study for treatment selection and a phase III study for efficacy confirmation. Furthermore, it is not uncommon to consider study endpoints with different treatment durations at different stages (see, e.g., Chow and Chang, 2006; Maca et al., 2006). Chow et al. (2007) and Lu et al. (2009) considered the cases where the study endpoints are continuous variables and binary responses, respectively. In this article, our attention is placed on the case where the study endpoints are time-to-event data with different treatment durations. For testing equality, superiority, and noninferiority/equivalence of two treatments, test statistics for the analysis of the combined data collected from the two stages are developed for Weibull distributed data. In addition, formulas for sample size calculation and sample size allocation between the two stages for each of the hypotheses are derived. Corresponding results are also derived under Cox's proportional hazards model.
近年来，在临床试验中使用两阶段无缝设计备受关注。两阶段无缝试验设计是指一种将通常为实现不同目标而分别进行的两项独立临床研究相结合的研究设计，例如用于治疗选择的II期研究和用于疗效确认的III期研究。此外，在不同阶段考虑具有不同治疗持续时间的研究终点并不罕见（例如，见Chow和Chang，2006年；Maca等人，2006年）。Chow等人（2007年）和Lu等人（2009年）分别考虑了研究终点为连续变量和二元反应的情况。在本文中，我们关注的是研究终点为具有不同治疗持续时间的事件发生时间数据的情况。为了检验两种治疗的相等性、优越性和非劣效性/等效性，针对威布尔分布数据，开发了用于分析从两个阶段收集的合并数据的检验统计量。此外，还推导了每个假设在两个阶段之间的样本量计算和样本量分配公式。在Cox比例风险模型下也得出了相应结果。
