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Int. J. Environ. Res. Public Health 2014, 11(10), 10951-10966; doi:10.3390/ijerph111010951

Effects of Non-Differential Exposure Misclassification on False Conclusions in Hypothesis-Generating Studies

1
Department of Environmental and Occupational Health, School of Public Health, Drexel University, Nesbitt Hall, 3215 Market Street, PA 19104, USA
2
Department of Epidemiology and Biostatistics, School of Public Health, Drexel University, Nesbitt Hall, 3215 Market Street, PA 19104, USA
3
Occupational and Public Health Division, ExxonMobil Biomedical Sciences Inc., 1545 U.S. Highway 22 East, Annandale, NJ 08801, USA
*
Author to whom correspondence should be addressed.
Received: 11 June 2014 / Revised: 11 October 2014 / Accepted: 14 October 2014 / Published: 21 October 2014
(This article belongs to the Special Issue Methodological Innovations and Reflections-1)
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Abstract

Despite the theoretical success of obviating the need for hypothesis-generating studies, they live on in epidemiological practice. Cole asserted that “… there is boundless number of hypotheses that could be generated, nearly all of them wrong” and urged us to focus on evaluating “credibility of hypothesis”. Adopting a Bayesian approach, we put this elegant logic into quantitative terms at the study planning stage for studies where the prior belief in the null hypothesis is high (i.e., “hypothesis-generating” studies). We consider not only type I and II errors (as is customary) but also the probabilities of false positive and negative results, taking into account typical imperfections in the data. We concentrate on a common source of imperfection in the data: non-differential misclassification of binary exposure classifier. In context of an unmatched case-control study, we demonstrate—both theoretically and via simulations—that although non-differential exposure misclassification is expected to attenuate real effect estimates, leading to the loss of ability to detect true effects, there is also a concurrent increase in false positives. Unfortunately, most investigators interpret their findings from such work as being biased towards the null rather than considering that they are no less likely to be false signals. The likelihood of false positives dwarfed the false negative rate under a wide range of studied settings. We suggest that instead of investing energy into understanding credibility of dubious hypotheses, applied disciplines such as epidemiology, should instead focus attention on understanding consequences of pursuing specific hypotheses, while accounting for the probability that the observed “statistically significant” association may be qualitatively spurious. View Full-Text
Keywords: false positive; false negative; Monte-Carlo simulation; study design; ase-control studies; measurement error; exposure misclassification; Bayesian; hypothesis-testing; power false positive; false negative; Monte-Carlo simulation; study design; ase-control studies; measurement error; exposure misclassification; Bayesian; hypothesis-testing; power
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Burstyn, I.; Yang, Y.; Schnatter, A.R. Effects of Non-Differential Exposure Misclassification on False Conclusions in Hypothesis-Generating Studies. Int. J. Environ. Res. Public Health 2014, 11, 10951-10966.

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