© 2004 by Oxford University Press
© 2004 Oxford University Press
COMMENTARY |
Assessing the Probability That a Positive Report is False: An Approach for Molecular Epidemiology Studies
Affiliations of authors: Biostatistics Branch (SW, LEg), Core Genotype Facility (SC), Hormonal and Reproductive Epidemiology Branch (MGC), and Occupational and Environmental Epidemiology Branch (NR), Division of Cancer Epidemiology and Genetics, and Pediatric Oncology Branch, Center for Cancer Research (SC), National Cancer Institute, National Institutes of Health, Bethesda, MD
Correspondence to: Sholom Wacholder, PhD, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7244 (e-mail: wacholder{at}nih.gov)
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.
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Correspondence about this Article
- Re: Assessing the Probability That a Positive Report is False: An Approach for Molecular Epidemiology Studies
- Hans-Hermann Dubben
J Natl Cancer Inst 2004 96: 1722.[Extract] [Full Text] [PDF]
- RESPONSE: Re: Assessing the Probability That a Positive Report is False: An Approach for Molecular Epidemiology Studies
- Sholom Wacholder, Stephen Chanock, Montserrat Garcia-Closas, Hormuzd A. Katki, Laure El ghormli, and Nathaniel Rothman
J Natl Cancer Inst 2004 96: 1722-1723.[Extract] [Full Text] [PDF]
Editorial about this Article
- Betting Odds and Genetic Associations
- Duncan C. Thomas and David G. Clayton
J Natl Cancer Inst 2004 96: 421-423.[Extract] [Full Text] [PDF]
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