title: Mediation analysis for survival data using semiparametric probit models.
abstract: Causal mediation modeling has become a popular approach for studying the effect of an exposure on an outcome through mediators. Currently, the literature on mediation analyses with survival outcomes largely focused on settings with a single mediator and quantified the mediation effects on the hazard, log hazard and log survival time (Lange and Hansen 2011; VanderWeele 2011). In this article, we propose a multi-mediator model for survival data by employing a flexible semiparametric probit model. We characterize path-specific effects (PSEs) of the exposure on the outcome mediated through specific mediators. We derive closed form expressions for PSEs on a transformed survival time and the survival probabilities. Statistical inference on the PSEs is developed using a nonparametric maximum likelihood estimator under the semiparametric probit model and the functional Delta method. Results from simulation studies suggest that our proposed methods perform well in finite sample. We illustrate the utility of our method in a genomic study of glioblastoma multiforme survival.
authors.affiliation: Departments of Epidemiology and Biostatistics, Brown University, 121 South Main Street, Providence, Rhode Island 02912, U.S.A.
authors.forename: Yen-Tsung
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, U.S.A.
authors.forename: Tianxi
authors.initials: T
authors.lastname: Cai
mesh_terms: D001699:Biometry / Q000379:methods; D015984:Causality; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D051383:GRB10 Adaptor Protein / Q000235:genetics; D023281:Genomics; D005909:Glioblastoma / Q000235:genetics / Q000401:mortality; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D011336:Probability; D016019:Survival Analysis
chemical_list: C096358:GRB10 protein, human; D051383:GRB10 Adaptor Protein
keywords: Causal mediation model; Integrative genomics; Nonparametric maximum likelihood estimator; Semiparametric probit model; Survival analysis