From testing to estimation: the problem of false positives in the context of carcinogen evaluation in the IARC monographs

Cancer Epidemiol Biomarkers Prev. 2012 Aug;21(8):1272-81. doi: 10.1158/1055-9965.EPI-12-0276. Epub 2012 Jun 19.

Abstract

Background: Cancer epidemiology has been criticized for producing false-positive associations. The present analysis investigates the frequency of and factors contributing to false-positive findings in cancer epidemiology.

Methods: The International Agency for Research on Cancer (IARC) Monographs Group 3 agents were examined to identify potential false-positive findings. Frequency estimates for their occurrence were calculated. Comments of the Working Groups on study quality were recorded for studies with potential false-positives. These were used to determine how many of such studies were criticized for each of the study quality factors that are suspected to contribute to false-positive results.

Results: Of 509 agents in group 3, 37 agents were found to have potential false-positive associations in the studies reviewed in their respective IARC monograph(s). The overall frequency of potential false-positives among these agents was between 0.03 and 0.10. The individual frequencies ranged from 0.01 to 0.40. The potential false-positive findings were produced by 162 studies. The most common factors contributing to potential false-positive findings were confounding and exposure misclassification.

Conclusions: The frequency estimates we have obtained do not suggest that epidemiology is grossly flooded by false-positive findings. The factors for which studies with potential false-positives were most often criticized were factors that are sometimes difficult to address in cancer epidemiologic research and can bias an effect estimate toward or away from the null.

Impact: The low frequency of false-positives in cancer epidemiology restores faith in epidemiologic procedures, making epidemiologic findings a useful guide for public health care measures.

MeSH terms

  • Carcinogenicity Tests / methods
  • Carcinogenicity Tests / standards*
  • Carcinogens / analysis
  • Carcinogens / toxicity*
  • Epidemiologic Methods
  • False Positive Reactions
  • Humans
  • Neoplasms / chemically induced*
  • Neoplasms / epidemiology*
  • Research Design

Substances

  • Carcinogens