Biomarker-Guided Adaptive Trial Designs in Phase II and Phase III: A Methodological Review.
Biomarker-Guided Adaptive Trial Designs in Phase II and Phase III: A Methodological Review.
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DOI：
10.1371/journal.pone.0149803
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kolamunnage-Dona R
中科院分区：
文献类型：
--
作者：
Antoniou M;Jorgensen AL;Kolamunnage-Dona R
个性化医疗是一个不断发展的研究领域，其目的是根据一个或多个个人特征为患者量身定制治疗。这些特征可以是人口统计学的，例如年龄或性别，或者生物学的，例如遗传或其他生物标志物。在临床实践中使用患者的生物标志物信息之前，必须在分析有效性、临床有效性和临床实用性方面进行稳健的测试。已经提出了许多临床试验设计来测试生物标志物的临床效用，包括旨在测试生物标志物指导的治疗方法的有效性的II期和III期临床试验;这些设计可以大致分为适应性和非适应性。虽然适应性设计允许基于试验期间积累的信息进行有计划的修改，但非适应性设计通常更简单，但灵活性较低。我们对过去十年中提出的生物标志物引导的适应性试验设计进行了全面审查。我们已经从107项研究中确定了8种不同的生物标志物引导的自适应设计和9种变化。在如何描述试验设计方面，特别是在不同作者使用的术语方面，观察到了很大的差异。我们以图形方式展示了当前生物标志物引导的适应性试验设计，并总结了每种设计的特征。我们的深入概述为未来的研究人员提供了明确的定义，方法和术语的生物标志物指导的适应性试验设计。
Personalized medicine is a growing area of research which aims to tailor the treatment given to a patient according to one or more personal characteristics. These characteristics can be demographic such as age or gender, or biological such as a genetic or other biomarker. Prior to utilizing a patient’s biomarker information in clinical practice, robust testing in terms of analytical validity, clinical validity and clinical utility is necessary. A number of clinical trial designs have been proposed for testing a biomarker’s clinical utility, including Phase II and Phase III clinical trials which aim to test the effectiveness of a biomarker-guided approach to treatment; these designs can be broadly classified into adaptive and non-adaptive. While adaptive designs allow planned modifications based on accumulating information during a trial, non-adaptive designs are typically simpler but less flexible. We have undertaken a comprehensive review of biomarker-guided adaptive trial designs proposed in the past decade. We have identified eight distinct biomarker-guided adaptive designs and nine variations from 107 studies. Substantial variability has been observed in terms of how trial designs are described and particularly in the terminology used by different authors. We have graphically displayed the current biomarker-guided adaptive trial designs and summarised the characteristics of each design. Our in-depth overview provides future researchers with clarity in definition, methodology and terminology for biomarker-guided adaptive trial designs.