title: Misclassification of the mediator matters when estimating indirect effects.
abstract: BACKGROUND
  Confounding of mediator-outcome associations resulting in collider biases causes systematic error when estimating direct and indirect effects. However, until recently little attention has been given to the impact of misclassification bias.
  
  
  OBJECTIVE
  To quantify the impact of non-differential and independent misclassification of a dichotomous exposure and a dichotomous mediator on three target parameters: the total effect of exposure on outcome; the direct effect (by conditioning on the mediator); and the indirect effect (identified by the percentage reduction in the excess OR on adjusting for the mediator).
  
  
  METHODS
  Simulations were conducted for varying strength of associations between exposure, mediator and outcome, varying ratios of exposed to unexposed and mediator present to mediator absent, and varying sensitivity and specificity of exposure and mediator classification.
  
  
  RESULTS
  ORs before (total effect) and after adjustment (direct effect) for the mediator are both biased towards the null by non-differential misclassification of the exposure, but the percentage reduction in the excess OR is little affected by misclassification of exposure. Conversely, misclassification of the mediator rapidly biases the percentage reduction of the excess OR (indirect effect) downwards.
  
  
  CONCLUSIONS
  If the research objective is to quantify the proportion of the total association that is due to mediation (ie, indirect effect), then minimising non-differential misclassification bias of the mediator is more important than that for the exposure. Misclassification bias is an important source of error when estimating direct and indirect effects.
authors: Health Inequalities Research Programme, Department of Public Health, University of Otago Wellington, Mein Street, Wellington, New Zealand. tony.blakely@otago.ac.nz
authors: Tony
authors: T
authors: Blakely
authors: Sarah
authors: S
authors: McKenzie
authors: Kristie
authors: K
authors: Carter
mesh_terms: D015982:Bias; D003198:Computer Simulation; D015986:Confounding Factors, Epidemiologic; D003627:Data Interpretation, Statistical; D015987:Effect Modifier, Epidemiologic; D006801:Humans; D016017:Odds Ratio; D012107:Research Design; D012942:Social Sciences / Q000379:methods*