Clinical trial designs incorporating predictive biomarkers.
Clinical trial designs incorporating predictive biomarkers.
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DOI：
10.1016/j.ctrv.2015.12.008
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发表时间：
2016-02
影响因子：
11.8
通讯作者：
Mandrekar SJ
中科院分区：
文献类型：
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作者：
Renfro LA;Mallick H;An MW;Sargent DJ;Mandrekar SJ
肿瘤治疗的开发传统上是在一系列临床试验中进行的，旨在评估同质（肿瘤类型和疾病阶段）患者人群的安全性（I期），初步疗效（II期）和标准治疗（III期）的改善。随着对癌症在分子水平上的了解越来越多，抑制特定癌细胞生长和存活机制的新型“靶向”药物增加了对新临床试验设计的需求，其中可以回答关于患者生物标志物和对治疗的反应之间的关系的相关问题。在此，我们回顾了临床试验设计文献，从最初到最近提出的靶向药物设计或假设在患者亚组中具有增强有效性的治疗（例如，具有特定生物标志物值或具有特定遗传肿瘤突变的人）。我们还描述了一些真实的临床试验中，生物标记物为基础的设计已被利用，包括讨论各自的优势和挑战。随着癌症根据个体患者和肿瘤特征进一步分类和/或重新分类，我们预计将继续需要新的试验设计，以跟上不断变化的临床癌症研究前沿。
Development of oncologic therapies has traditionally been performed in a sequence of clinical trials intended to assess safety (phase I), preliminary efficacy (phase II), and improvement over the standard of care (phase III) in homogeneous (in terms of tumor type and disease stage) patient populations. As cancer has become increasingly understood on the molecular level, newer “targeted” drugs that inhibit specific cancer cell growth and survival mechanisms have increased the need for new clinical trial designs, wherein pertinent questions on the relationship between patient biomarkers and response to treatment can be answered. Herein, we review the clinical trial design literature from initial to more recently proposed designs for targeted agents or those treatments hypothesized to have enhanced effectiveness within patient subgroups (e.g., those with a certain biomarker value or who harbor a certain genetic tumor mutation). We also describe a number of real clinical trials where biomarker-based designs have been utilized, including a discussion of their respective advantages and challenges. As cancers become further categorized and/or reclassified according to individual patient and tumor features, we anticipate a continued need for novel trial designs to keep pace with the changing frontier of clinical cancer research.
直接分配选项作为模块化设计组件：两个预定义亚组设置的示例。
影响因子：
--
作者：
An MW;Lu X;Sargent DJ;Mandrekar SJ
通讯作者：
Mandrekar SJ