Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
Stat Med. 2011 Jul 30;30(17):2171-86. doi: 10.1002/sim.4251. Epub 2011 May 17.
Recently, global drug developments have attracted much attention from sponsors as well as regulatory authorities. The ICH E5 guideline defines a bridging study as a supplementary study conducted in the new region to provide pharmacodynamic or clinical data on efficacy, safety, dosage, and dose regimen to allow extrapolation of the foreign clinical data to the population of the new region. On the other hand, a multi-regional trial may incorporate subjects from many regions around the world under the same protocol so that after showing the overall efficacy of a drug in all global regions, we can simultaneously evaluate the possibility of applying the overall trial results to each region and consequently support drug registration in each region. In this paper, we develop a consistency approach for assessment of similarity between a bridging study conducted in a new region and studies conducted in the original region. A statistical criterion is also established to assess the consistency between the region of interest and overall results in a multi-regional trial. The method for sample size determination for the bridging study is also proposed. Numerical examples illustrate applications of the proposed approaches in different scenarios.
最近，全球药物开发引起了赞助商和监管机构的极大关注。ICH E5 指南将桥接研究定义为在新地区进行的补充研究，以提供药效学或临床疗效、安全性、剂量和剂量方案的数据，从而将国外临床数据外推到新地区的人群。另一方面，多区域试验可以在同一方案下纳入来自世界各地的受试者，以便在显示药物在所有全球区域的总体疗效后，我们可以同时评估将总体试验结果应用于每个区域的可能性，并因此支持每个区域的药物注册。在本文中，我们开发了一种一致性方法来评估在新地区进行的桥接研究与在原始地区进行的研究之间的相似性。还建立了一个统计标准来评估多区域试验中关注区域与总体结果之间的一致性。还提出了桥接研究的样本量确定方法。数值示例说明了所提出方法在不同情况下的应用。
