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解读随机对照试验结果中的地域差异
Interpreting Geographic Variations in Results of Randomized, Controlled Trials


Salim Yusuf ... 其他 • 2016.12.08

临床试验者们普遍接受的一个前提是,在随机对照试验的亚组中出现的令人意外的结果最有可能出于偶然。正如我们在近30年前写的那样:“我们认为,与从随机临床试验的各亚组中单独观察到的疗效相比,利用整体‘平均’的结果对疗效的估计通常更为可信1。”在我们写下这些文字时,包含患者的遗传标志或特定生物靶点的试验还不常见。如今,对这些靶点定义的亚组的分析,是从对各亚组独特的效应进行特定的推断的角度进行的;而我们相信应该如此。与之相似,在20世纪80年代,跨国试验十分少见;如今则有很多跨国试验。本文论述了如何解读在以国家或地域划分的亚组间观察到的疗效差异的问题。我们没有试图阐述在各独立试验机构观察到的疗效差异,因为在大多数多中心试验中,各个试验单位的样本量过小,不能可靠地得到疗效估算。

跨国试验数量的增加源于人们意识到大多数治疗和预防策略,特别是对于常见疾病,在主要结局上最多只有中等程度的获益(例如,死亡、心脏病或癌症复发的相对风险降低10%~25%)。为了可靠地检测到这种中等程度的获益,试验通常需要获取几百至上千个所关注的结局,这意味着试验需要包含上千名,乃至上万名在险受试者。获得如此众多的受试者需要几个国家(在某些试验中,多达50个国家)2的多个试验点(通常需要几百个)之间的合作。涉及非常见疾病的患者的试验可能也需要多个国家的试验机构,因为单从一个国家不可能获得足够数量的参与者。因此,在每个国家通常只能入组少量患者(通常不多于5个或10个)。更为常见的情况是,如果干预治疗的申办方希望获得多个国家监管机构的批准,那么跨国研究可能是必需的。





作者信息

Salim Yusuf, M.B., B.S., D.Phil., and Janet Wittes, Ph.D.
From the Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada (S.Y.); and Statistics Collaborative, Washington, DC (J.W.). Address reprint requests to Dr. Yusuf at the Population Health Research Institute, 237 Barton St. E., Hamilton, ON L8L 2X2, Canada, or at yusufs@mcmaster.ca.

 

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