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评估阳性报告为假的概率:分子流行病学研究方法

Assessing the probability that a positive report is false: an approach for molecular epidemiology studies.

作者信息

Wacholder Sholom, Chanock Stephen, Garcia-Closas Montserrat, El Ghormli Laure, Rothman Nathaniel

机构信息

Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7244, USA.

出版信息

J Natl Cancer Inst. 2004 Mar 17;96(6):434-42. doi: 10.1093/jnci/djh075.

Abstract

Too many reports of associations between genetic variants and common cancer sites and other complex diseases are false positives. A major reason for this unfortunate situation is the strategy of declaring statistical significance based on a P value alone, particularly, any P value below.05. The false positive report probability (FPRP), the probability of no true association between a genetic variant and disease given a statistically significant finding, depends not only on the observed P value but also on both the prior probability that the association between the genetic variant and the disease is real and the statistical power of the test. In this commentary, we show how to assess the FPRP and how to use it to decide whether a finding is deserving of attention or "noteworthy." We show how this approach can lead to improvements in the design, analysis, and interpretation of molecular epidemiology studies. Our proposal can help investigators, editors, and readers of research articles to protect themselves from overinterpreting statistically significant findings that are not likely to signify a true association. An FPRP-based criterion for deciding whether to call a finding noteworthy formalizes the process already used informally by investigators--that is, tempering enthusiasm for remarkable study findings with considerations of plausibility.

摘要

关于基因变异与常见癌症部位及其他复杂疾病之间关联的报告,有太多都是假阳性结果。造成这种不幸局面的一个主要原因是仅基于P值来判定统计学显著性的策略,尤其是任何低于0.05的P值。假阳性报告概率(FPRP),即在统计学显著结果的情况下基因变异与疾病之间不存在真实关联的概率,不仅取决于观察到的P值,还取决于基因变异与疾病之间关联为真的先验概率以及检验的统计效力。在这篇评论中,我们展示了如何评估FPRP以及如何用它来决定一个发现是否值得关注或“值得注意”。我们展示了这种方法如何能改进分子流行病学研究的设计、分析和解释。我们的提议可以帮助研究文章的研究者、编辑和读者避免过度解读那些不太可能意味着真实关联的统计学显著结果。基于FPRP的判定一个发现是否值得注意的标准,将研究者已经在非正式使用的过程形式化了——也就是说,通过考虑合理性来抑制对显著研究发现的热情。

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