title: Covariate measurement error correction methods in mediation analysis with failure time data.
abstract: Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This article focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error, and error associated with temporal variation. The underlying model with the "true" mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean-variance regression calibration approach and a follow-up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case-cohort and nested case-control sampling designs. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk.
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, U.S.A.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhao
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
mesh_terms: D000465:Algorithms; D016477:Artifacts; D001943:Breast Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects / Q000706:statistics & numerical data*; D006801:Humans; D015994:Incidence; D017698:Postmenopause / Q000187:drug effects*; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
keywords: Cox model; Mean-variance estimating functions; Measurement error; Mediation analysis; Regression calibration