Hirakawa Akihiro, Asano Junichi, Sato Hiroyuki, Teramukai Satoshi
Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8654, Japan.
Biostatistics Group, Center for Product Evaluation, Pharmaceuticals and Medical Devices Agency, Tokyo, 100-0013, Japan.
Contemp Clin Trials Commun. 2018 Aug 24;12:1-8. doi: 10.1016/j.conctc.2018.08.009. eCollection 2018 Dec.
In oncology, next generation sequencing and comprehensive genomic profiling have enabled the detailed classification of tumors using molecular biology. However, it is unrealistic to conduct phase I-III trials according to each sub-population based on patient molecular subtypes. Common protocols that assess the combination of several molecular markers and their targeted therapies by means of multiple sub-studies are required. These protocols are called "master protocols," and are drawing attention as a next-generation clinical trial design. Recently, several reviews of clinical trials based on the master protocol design have been published, but their definitions of these such trials, including basket, umbrella, and platform trials, were not consistent. Concurrently, the acceleration of the development of new statistical designs for master protocol trials has been underway. This article provides an overview of recent reviews for master protocols, including their statistical design methodologies in Oncology. We also introduce several examples of previous and on-going master protocol trials along with their classifications by some recent studies.
在肿瘤学领域，新一代测序和全面基因组分析已能够利用分子生物学对肿瘤进行详细分类。然而，根据患者分子亚型针对每个亚群开展I至III期试验是不现实的。需要通过多个子研究来评估多种分子标志物及其靶向治疗组合的通用方案。这些方案被称为“主方案”，作为一种下一代临床试验设计正受到关注。最近，已经发表了几篇基于主方案设计的临床试验综述，但它们对这类试验（包括篮子试验、伞形试验和平台试验）的定义并不一致。与此同时，主方案试验新统计设计的开发加速正在进行中。本文概述了近期关于主方案的综述，包括其在肿瘤学中的统计设计方法。我们还介绍了一些既往和正在进行的主方案试验的例子，以及近期一些研究对它们的分类。
