title: Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations.
abstract: This article investigates a generalized semiparametric varying-coefficient model for longitudinal data that can flexibly model three types of covariate effects: time-constant effects, time-varying effects, and covariate-varying effects. Different link functions can be selected to provide a rich family of models for longitudinal data. The model assumes that the time-varying effects are unspecified functions of time and the covariate-varying effects are parametric functions of an exposure variable specified up to a finite number of unknown parameters. The estimation procedure is developed using local linear smoothing and profile weighted least squares estimation techniques. Hypothesis testing procedures are developed to test the parametric functions of the covariate-varying effects. The asymptotic distributions of the proposed estimators are established. A working formula for bandwidth selection is discussed and examined through simulations. Our simulation study shows that the proposed methods have satisfactory finite sample performance. The proposed methods are applied to the ACTG 244 clinical trial of HIV infected patients being treated with Zidovudine to examine the effects of antiretroviral treatment switching before and after HIV develops the T215Y/F drug resistance mutation. Our analysis shows benefits of treatment switching to the combination therapies as compared to continuing with ZDV monotherapy before and after developing the 215-mutation.
authors.affiliation: Biostatistics and Programming, Sanofi, Bridgewater, New Jersey 08807, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Mathematics and Statistics, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.|Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
mesh_terms: D003198:Computer Simulation; D006801:Humans; D016018:Least-Squares Analysis; D011897:Random Allocation; D012107:Research Design
keywords: ACTG 244 AIDS clinical trial; Adaptive treatment randomization; Covariate-varying effects; Hypothesis tests; Link function; Longitudinal data analysis; Profile weighted least squares