Reports from the 2010 Clinical and Translational Cancer Research Think Tank meeting: design strategies for personalized therapy trials.
Reports from the 2010 Clinical and Translational Cancer Research Think Tank meeting: design strategies for personalized therapy trials.
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DOI：
10.1158/1078-0432.ccr-11-2018
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发表时间：
2012-02-01
期刊：
影响因子：
--
通讯作者：
Rubin EH
中科院分区：
文献类型：
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作者：
Berry DA;Herbst RS;Rubin EH
癌症是一种异质性疾病，这一点早已得到证实。但直到最近，我们才意识到异质性的程度。没有一种单一疗法对具有相同组织学的肿瘤的每个患者都有效。基于单一治疗方法的临床策略导致大多数患者过度治疗。生物标志物就像一把刀，把疾病切割得更细。临床研究的未来将基于了解特定疗法是否比其他疗法更适合某些生物标志物定义的子集。治疗最终将针对狭窄的生物标志物子集。确定哪些疗法适合哪些患者需要生物科学和临床试验的经验证据。这两个方面都不容易。在这篇文章中，我们描述了一些新生的方法来设计临床试验，是基于生物标志物和自适应。我们的重点是同时解决许多问题的适应性试验。在某种程度上，这些临床实验本身就是一个更大的实验的一部分：学习是否以及如何设计实验，将小部分疾病的患者与特别有效甚至可能治愈的治疗方法相匹配。
It has long been evident that cancer is a heterogeneous disease. But only relatively recently have we come to realize the extent of the heterogeneity. No single therapy is effective for every patient with tumors having the same histology. A clinical strategy based on a single-therapy approach results in overtreatment for the majority of patients. Biomarkers are knives slicing the disease ever more finely. The future of clinical research will be based on learning whether particular therapies are more appropriate for some biomarker-defined subsets than are other therapies. Therapies will eventually be tailored to narrow biomarker subsets. Determining which therapies are appropriate for which patients requires both biological science and empirical evidence from clinical trials. Neither aspect is easy. In this essay we describe some nascent approaches to designing clinical trials that are biomarker-based and adaptive. Our focus is on adaptive trials that address many questions at once. In a way these clinical experiments are themselves part of a much larger experiment: learning whether and how it is possible to design experiments that match patients in small subsets of disease with a therapies that are especially effective and possibly even curative for them.