Sources of Bias in Specimens for Research About Molecular Markers for Cancer
Sources of Bias in Specimens for Research About Molecular Markers for Cancer
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DOI：
10.1200/jco.2009.25.6065
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发表时间：
2010-02-01
影响因子：
45.3
通讯作者：
Gourlay, Margaret L.
中科院分区：
文献类型：
--
作者：
Ransohoff, David F.;Gourlay, Margaret L.
当癌症与正常人之间的“区别”是由于偏倚，即比较组之间的系统性差异时，关于标记物诊断或预后准确性的声明往往令人失望。本文描述了一个框架，以帮助简化和组织标记物研究中的当前问题，重点是样本的作用，作为观察性研究中的偏差来源，并使用该重点来解决问题，提高可靠性。其中心思想是，关于标记的研究中的“基本比较”（即评估标记是否具有歧视性的比较）涉及两个由样本“连接”的不同过程。如果受试者选择（第一个过程）在比较的组之间产生基线不平等，则标本的实验室分析（第二个过程）可能错误地发现阳性结果。虽然这两个过程都很重要，但受试者的选择对标记物研究的质量有更根本的影响，因为它可以以一种无法通过实验室分析中的任何改进来纠正的方式将偏差硬连接到所有比较中。认识到这两个过程的独立性，并让具有适当专业知识的研究人员负责这两个过程，可能会增加癌症生物标志物研究的可靠性。
Claims about the diagnostic or prognostic accuracy of markers often prove disappointing when "discrimination" found between cancers versus normals is due to bias, a systematic difference between compared groups. This article describes a framework to help simplify and organize current problems in marker research by focusing on the role of specimens as a source of bias in observational research and using that focus to address problems and improve reliability. The central idea is that the "fundamental comparison" in research about markers (ie, the comparison done to assess whether a marker discriminates) involves two distinct processes that are "connected" by specimens. If subject selection (first process) creates baseline inequality between groups being compared, then laboratory analysis of specimens (second process) may erroneously find positive results. Although both processes are important, subject selection more fundamentally influences the quality of marker research, because it can hardwire bias into all comparisons in a way that cannot be corrected by any refinement in laboratory analysis. An appreciation of the separateness of these two processes-and placing investigators with appropriate expertise in charge of each-may increase the reliability of research about cancer biomarkers.