Instrumental variable estimation in semi-parametric additive hazards models.

Instrumental variable methods allow unbiased estimation in the presence of unmeasured confounders when an appropriate instrumental variable is available. Two-stage least-squares and residual inclusion methods have recently been adapted to additive hazard models for censored survival data. The semi-parametric additive hazard model which can include time-independent and time-dependent covariate effects is particularly suited for the two-stage residual inclusion method, since it allows direct estimation of time-independent covariate effects without restricting the effect of the residual on the hazard. In this article, we prove asymptotic normality of two-stage residual inclusion estimators of regression coefficients in a semi-parametric additive hazard model with time-independent and time-dependent covariate effects. We consider the cases of continuous and binary exposure. Estimation of the conditional survival function given observed covariates is discussed and a resampling scheme is proposed to obtain simultaneous confidence bands. The new methods are compared to existing ones in a simulation study and are applied to a real data set. The proposed methods perform favorably especially in cases with exposure-dependent censoring.