title: Instrumental variable additive hazards models.
abstract: Instrumental variable (IV) methods are popular in non-experimental studies to estimate the causal effects of medical interventions. These approaches allow for the consistent estimation of treatment effects even if important confounding factors are unobserved. Despite the increasing use of these methods, there have been few extensions of IV methods to censored data problems. In this article, we discuss challenges in applying IV techniques to the proportional hazards model and demonstrate the utility of the additive hazards formulation for IV analyses with censored data. Assuming linear structural equation models for the hazard function, we develop a closed-form, two-stage estimator for the causal effect in the additive hazard model. The methods permit both continuous and discrete exposures, and enable the estimation of causal relative survival measures. The asymptotic properties of the estimators are derived and the resulting inferences are shown to perform well in simulation studies and in an application to a data set on the effectiveness of a novel chemotherapeutic agent for colon cancer.
authors.affiliation: Department of Statistics and Applied Probability, National University of Singapore, Singapore, 117946, Singapore.|Duke-NUS Graduate Medical School, Singapore, 169857, Singapore.|Singapore Eye Research Institute, Singapore.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Statistics and Biostatistics, University of North Carolina, Chapel Hill, North Carolina, U.S.A.
authors.forename: Jason
authors.initials: J
authors.lastname: Fine
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, U.S.A.
authors.forename: Alan
authors.initials: A
authors.lastname: Brookhart
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D003627:Data Interpretation, Statistical; D006801:Humans; D015995:Prevalence; D016016:Proportional Hazards Models; D018570:Risk Assessment / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Additive hazards model; Instrumental variable; Survival analysis; Two-stage least squares estimation