Tu, WanzhuHe, ZangdongYu, ZhangshengLiu, HaiSong, Yiqing2015-05-122015-05-122014https://hdl.handle.net/1805/6365http://dx.doi.org/10.7912/C2/2780Indiana University-Purdue University Indianapolis (IUPUI)Joint models of longitudinal and survival outcomes have been used with increasing frequency in clinical investigations. Correct specification of fixed and random effects, as well as their functional forms is essential for practical data analysis. However, no existing methods have been developed to meet this need in a joint model setting. In this dissertation, I describe a penalized likelihood-based method with adaptive least absolute shrinkage and selection operator (ALASSO) penalty functions for model selection. By reparameterizing variance components through a Cholesky decomposition, I introduce a penalty function of group shrinkage; the penalized likelihood is approximated by Gaussian quadrature and optimized by an EM algorithm. The functional forms of the independent effects are determined through a procedure for structural discovery. Specifically, I first construct the model by penalized cubic B-spline and then decompose the B-spline to linear and nonlinear elements by spectral decomposition. The decomposition represents the model in a mixed-effects model format, and I then use the mixed-effects variable selection method to perform structural discovery. Simulation studies show excellent performance. A clinical application is described to illustrate the use of the proposed methods, and the analytical results demonstrate the usefulness of the methods.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesJoint modelsMixed effect selectionStructural discoveryAdaptive LASSOGaussian quadratureEM algorithmGaussian quadrature formulas -- Research -- AnalysisLinear models (Statistics) -- Research -- AnalysisExpectation-maximization algorithms -- ResearchRegression analysis -- Data processingNumerical analysis -- Data processingSurvival analysis (Biometry) -- Data processingSpectral theory (Mathematics)Mathematical statistics -- Longitudinal studiesEstimation theory -- AnalysisStatistics -- Data processingCalculus of variationsStructural bioinformaticsParameter estimationThesis