Assessment of vibration of effects due to model specification can demonstrate the instability of observational associations

J Clin Epidemiol. 2015 Sep;68(9):1046-58. doi: 10.1016/j.jclinepi.2015.05.029. Epub 2015 Jun 6.

Abstract

Objectives: Model specification-what adjusting variables are analytically modeled-may influence results of observational associations. We present a standardized approach to quantify the variability of results obtained with choices of adjustments called the "vibration of effects" (VoE).

Study design and setting: We estimated the VoE for 417 clinical, environmental, and physiological variables in association with all-cause mortality using National Health and Nutrition Examination Survey data. We selected 13 variables as adjustment covariates and computed 8,192 Cox models for each of 417 variables' associations with all-cause mortality.

Results: We present the VoE by assessing the variance of the effect size and in the -log10(P-value) obtained by different combinations of adjustments. We present whether there are multimodality patterns in effect sizes and P-values and the trajectory of results with increasing adjustments. For 31% of the 417 variables, we observed a Janus effect, with the effect being in opposite direction in the 99th versus the 1st percentile of analyses. For example, the vitamin E variant α-tocopherol had a VoE that indicated higher and lower risk for mortality.

Conclusion: Estimating VoE offers empirical estimates of associations are under different model specifications. When VoE is large, claims for observational associations should be very cautious.

Keywords: Biostatistics; Confounding; Environment-wide association study; Model specification; Observational association; Vibration of effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Confounding Factors, Epidemiologic
  • Environmental Exposure / statistics & numerical data
  • Epidemiologic Methods*
  • Humans
  • Models, Statistical
  • Mortality / trends*
  • Nutrition Surveys
  • Observational Studies as Topic
  • Phenotype
  • Risk Assessment
  • United States / epidemiology
  • Vitamin E / administration & dosage

Substances

  • Vitamin E