Approaches to evaluation of treatment effect in randomized clinical trials with genomic subset
Approaches to evaluation of treatment effect in randomized clinical trials with genomic subset
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DOI：
10.1002/pst.300
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发表时间：
2007-07-01
影响因子：
1.5
通讯作者：
Hung, H. M. James
中科院分区：
文献类型：
--
作者：
Wang, Sue-Jane;O'Neill, Robert T.;Hung, H. M. James
随着人类基因组/遗传学研究的进展，临床试验界逐渐认识到，表型相同的患者在基因组水平可能存在差异。基因组技术为开发一种基因组（复合）生物标志物提供了一种可能的途径，以预测可能（更）有可能从治疗中获益的对基因组有反应的患者亚群。随机对照试验是为一种新疗法可能显示的据称效果提供具有科学说服力证据的主要手段。在传统临床试验中，主要临床假设涉及由主要疗效终点定义的所有符合研究条件的患者的治疗效果。传统设计中“一刀切”的方面受到了挑战，特别是当疾病由于可观察到的临床特征和/或不可观察到的潜在基因组特征而可能存在异质性时。从传统的单一人群设计目标扩展到包含两种可能的患者人群的目标，将能够对药物反应程度不同的患者进行更有信息量的评估。在传统临床试验的基础上增加一个基因组目标，可以从患者的角度构建一个有吸引力的概念框架，以便在严格控制的临床试验中实现个性化医疗。个性化医疗有许多被认为的益处，这些益处基于在疾病识别以及疾病预防或复发方面采取基因组主动措施的理念。在本文中，我们表明，可以构建一种适应性设计方法，以便比传统的非适应性方法更有效地研究总体治疗效果的临床假设以及基因组亚群中的治疗效果假设。2007年由约翰威立父子有限公司出版。
With the advances in human genomic/genetic studies, the clinical trial community gradually recognizes that phenotypically homogeneous patients may be heterogeneous at the genomic level. The genomic technology brings a possible avenue for developing a genomic (composite) biomarker to predict a genomically responsive patient subset that may have a (much) higher likelihood of benefiting from a treatment.Randomized controlled trial is the mainstay to provide scientifically convincing evidence of a purported effect a new treatment may demonstrate. In conventional clinical trials, the primary clinical hypothesis pertains to the therapeutic effect in all patients who are eligible for the study defined by the primary efficacy endpoint. The aspect of one-size-fits-all surrounding the conventional design has been challenged, particularly when the diseases may be heterogeneous due to observable clinical characteristics and/or unobservable underlying the genomic characteristics.Extension from the conventional single population design objective to an objective that encompasses two possible patient populations will allow more informative evaluation in the patients having different degrees of responsiveness to medication. Building in conventional clinical trials, an additional genomic objective can generate an appealing conceptual framework from the patient's perspective in addressing personalized medicine in well-controlled clinical trials. There are many perceived benefits of personalized medicine that are based on the notion of being genomically proactive in the identification of disease and prevention of disease or recurrence. In this paper, we show that an adaptive design approach can be constructed to study a clinical hypothesis of overall treatment effect and a hypothesis of treatment effect in a genomic subset more efficiently than the conventional nonadaptive approach. Published in 2007 by John Wiley & Sons, Ltd.