Criteria for the use of omics-based predictors in clinical trials: explanation and elaboration.
Criteria for the use of omics-based predictors in clinical trials: explanation and elaboration.
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DOI：
10.1186/1741-7015-11-220
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发表时间：
2013-10-17
期刊：
影响因子：
9.3
通讯作者：
Conley BA
中科院分区：
文献类型：
--
作者：
McShane LM;Cavenagh MM;Lively TG;Eberhard DA;Bigbee WL;Williams PM;Mesirov JP;Polley MY;Kim KY;Tricoli JV;Taylor JM;Shuman DJ;Simon RM;Doroshow JH;Conley BA
高通量组学?生成生物标本分子图谱的技术已广泛用于临床前研究，以揭示分子亚型和阐明疾病的生物学机制，并在临床标本的回顾性研究中建立数学模型以预测临床终点。然而，将这些技术转化为对指导患者管理决策有用的临床试验一直相对缓慢。很难确定基于组学的测试的证据体何时足够全面和可靠，以支持其已准备好用于临床应用的主张，或者甚至已准备好在临床试验中进行明确评估，以便用于指导患者治疗。造成这种困难的原因包括许多这些研究的探索性和回顾性，这些分析的复杂性及其在临床标本中的应用，以及从这些组学技术产生的非常高维数据中开发数学预测模型所固有的许多潜在陷阱。在这里，我们提出了一份标准清单，在评估支持临床使用预测器来指导患者治疗的证据时要考虑。包括与标本和分析要求有关的问题，开发预测模型过程的合理性，对临床研究设计和行为的期望，以及对监管、伦理和法律问题的关注。拟议的检查表应作为一份有用的指南，供研究人员为涉及使用基于组学的测试的研究提出建议。美国国家癌症研究所计划在审查涉及组学测试的研究提案时参考这些指南，并希望其他赞助者也能采用清单。
High-throughput ?omics? technologies that generate molecular profiles for biospecimens have been extensively used in preclinical studies to reveal molecular subtypes and elucidate the biological mechanisms of disease, and in retrospective studies on clinical specimens to develop mathematical models to predict clinical endpoints. Nevertheless, the translation of these technologies into clinical tests that are useful for guiding management decisions for patients has been relatively slow. It can be difficult to determine when the body of evidence for an omics-based test is sufficiently comprehensive and reliable to support claims that it is ready for clinical use, or even that it is ready for definitive evaluation in a clinical trial in which it may be used to direct patient therapy. Reasons for this difficulty include the exploratory and retrospective nature of many of these studies, the complexity of these assays and their application to clinical specimens, and the many potential pitfalls inherent in the development of mathematical predictor models from the very high-dimensional data generated by these omics technologies. Here we present a checklist of criteria to consider when evaluating the body of evidence supporting the clinical use of a predictor to guide patient therapy. Included are issues pertaining to specimen and assay requirements, the soundness of the process for developing predictor models, expectations regarding clinical study design and conduct, and attention to regulatory, ethical, and legal issues. The proposed checklist should serve as a useful guide to investigators preparing proposals for studies involving the use of omics-based tests. The US National Cancer Institute plans to refer to these guidelines for review of proposals for studies involving omics tests, and it is hoped that other sponsors will adopt the checklist as well.
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