Huang Qin, Chen Gang, Yuan Zhilong, Lan K K Gordon
Office of Biostatistics, Center for Drug Evaluation, SFDA, Beijing, PR China.
J Biopharm Stat. 2012 Sep;22(5):1060-73. doi: 10.1080/10543406.2012.701587.
Due to the potential impact of ethnic factors on clinical outcomes, the global registration of a new treatment is challenging. China and Japan often require local trials in addition to a multiregional clinical trial (MRCT) to support the efficacy and safety claim of the treatment. The impact of ethnic factors on the treatment effect has been intensively investigated and discussed from different perspectives. However, most current methods are focusing on the assessment of the consistency or similarity of the treatment effect between different ethnic groups in exploratory nature. In this article, we propose a new method for the design and sample size consideration for a simultaneous global drug development program (SGDDP) using weighted z-tests. In the proposed method, to test the efficacy of a new treatment for the targeted ethnic (TE) group, a weighted test that combines the information collected from both the TE group and the nontargeted ethnic (NTE) group is used. The influence of ethnic factors and local medical practice on the treatment effect is accounted for by down-weighting the information collected from NTE group in the combined test statistic. This design controls rigorously the overall false positive rate for the program at a given level. The sample sizes needed for the TE group in an SGDDP for three most commonly used efficacy endpoints, continuous, binary, and time-to-event, are then calculated.
由于种族因素对临床结果可能产生影响，新疗法的全球注册具有挑战性。中国和日本除多区域临床试验（MRCT）外，通常还要求进行本地试验，以支持该疗法的疗效和安全性声明。种族因素对治疗效果的影响已从不同角度进行了深入研究和讨论。然而，目前大多数方法主要是探索性地评估不同种族群体之间治疗效果的一致性或相似性。在本文中，我们提出了一种使用加权z检验进行同步全球药物开发计划（SGDDP）设计和样本量考量的新方法。在所提出的方法中，为了检验针对目标种族（TE）群体的新疗法的疗效，使用了一种结合从TE群体和非目标种族（NTE）群体收集的信息的加权检验。在合并检验统计量中，通过对从NTE群体收集的信息进行降权，来考虑种族因素和当地医疗实践对治疗效果的影响。这种设计在给定水平上严格控制了该计划的总体假阳性率。然后计算了SGDDP中TE群体针对三种最常用疗效终点（连续型、二项型和事件发生时间）所需的样本量。
