Mediation analysis in the presence of continuous exposure measurement error

The difference method is used in mediation analysis to quantify the extent to which a mediator explains the mechanisms underlying the pathway between an exposure and an outcome. In many health science studies, the exposures are almost never measured without error, which can result in biased effect estimates. This article investigates methods for mediation analysis when a continuous exposure is mismeasured. Under a linear exposure measurement error model, we prove that the bias of indirect effect and mediation proportion can go in either direction but the mediation proportion is usually be less biased when the associations between the exposure and its error-prone counterpart are similar with and without adjustment for the mediator. We further propose methods to adjust for exposure measurement error with continuous and binary outcomes. The proposed approaches require a main study/validation study design where in the validation study, data are available for characterizing the relationship between the true exposure and its error-prone counterpart. The proposed approaches are then applied to the Health Professional Follow-up Study, 1986-2016, to investigate the impact of body mass index (BMI) as a mediator for mediating the effect of physical activity on the risk of cardiovascular diseases. Our results reveal that physical activity is significantly associated with a lower risk of cardiovascular disease incidence, and approximately half of the total effect of physical activity is mediated by BMI after accounting for exposure measurement error. Extensive simulation studies are conducted to demonstrate the validity and efficiency of the proposed approaches in finite samples.