Nonlinear mixed-effects models are very useful to analyze repeated measures data and are used in ... more Nonlinear mixed-effects models are very useful to analyze repeated measures data and are used in a variety of applications. Normal distributions for random effects and residual errors are usually assumed, but such assumptions make inferences vulnerable to the presence of outliers. In this work, we introduce an extension of a normal nonlinear mixed-effects model considering a subclass of elliptical contoured distributions for both random effects and residual errors. This elliptical subclass, the scale mixtures of normal (SMN) distributions, includes heavy-tailed multivariate distributions, such as Student-t, the contaminated normal and slash, among others, and represents an interesting alternative to outliers accommodation maintaining the elegance and simplicity of the maximum likelihood theory. We propose an exact estimation procedure to obtain the maximum likelihood estimates of the fixed-effects and variance components, using a stochastic approximation of the EM algorithm. We compare the performance of the normal and the SMN models with two real data sets.
The EM algorithm and its extensions are very popular tools for maximum likelihood estimation in i... more The EM algorithm and its extensions are very popular tools for maximum likelihood estimation in incomplete data setting. However, one of the limitations of these methods is their slow convergence. The PX-EM (parameter-expanded EM) algorithm was proposed by Liu, Rubin and Wu to make EM much faster. On the other hand, stochastic versions of EM are powerful alternatives of EM when the E-step is untractable in a closed form. In this paper we propose the PX-SAEM which is a parameter expansion version of the so-called SAEM (Stochastic Approximation version of EM). PX-SAEM is shown to accelerate SAEM and improve convergence toward the maximum likelihood estimate in a parametric framework. Numerical examples illustrate the behavior of PX-SAEM in linear and nonlinear mixed effects models.
The analysis of nonlinear function-valued characters is very important in genetic studies, especi... more The analysis of nonlinear function-valued characters is very important in genetic studies, especially for growth traits of agricultural and laboratory species. Inference in nonlinear mixed effects models is, however, quite complex and is usually based on likelihood approximations or Bayesian methods. The aim of this paper was to present an efficient stochastic EM procedure, namely the SAEM algorithm, which is much faster to converge than the classical Monte Carlo EM algorithm and Bayesian estimation procedures, does not require specification of prior distributions and is quite robust to the choice of starting values. The key idea is to recycle the simulated values from one iteration to the next in the EM algorithm, which considerably accelerates the convergence. A simulation study is presented which confirms the advantages of this estimation procedure in the case of a genetic analysis. The SAEM algorithm was applied to real data sets on growth measurements in beef cattle and in chickens. The proposed estimation procedure, as the classical Monte Carlo EM algorithm, provides significance tests on the parameters and likelihood based model comparison criteria to compare the nonlinear models with other longitudinal methods. genetic analysis / growth curves / longitudinal data / stochastic approximation EM algorithm
Generalized linear mixed models (GLMM) form a very general class of random effects models for dis... more Generalized linear mixed models (GLMM) form a very general class of random effects models for discrete and continuous responses in the exponential family. They are useful in a variety of applications. The traditional likelihood approach for GLMM usually involves high dimensional integrations which are computationally intensive. In this work, we investigate the case of binary outcomes analyzed under a two stage probit normal model with random effects. First, it is showed how ML estimates of the fixed effects and variance components can be computed using a stochastic approximation of the EM algorithm (SAEM). The SAEM algorithm can be applied directly, or in conjunction with a parameter expansion version of EM to speed up the convergence. A procedure is also proposed to obtain REML estimates of variance components and REML-based estimates of fixed effects. Finally an application to a real data set involving a clinical trial is presented in which these techniques are compared to other procedures (PQL, ML, Bayes) already available in classical softwares (SAS Glimmix, SAS Nlmixed, WinBUGS).
The analysis of nonlinear function-valued characters is very important in genetic studies, especi... more The analysis of nonlinear function-valued characters is very important in genetic studies, especially for growth traits of agricultural and laboratory species. Inference in nonlinear mixed effects models is, however, quite complex and is usually based on likelihood approximations or Bayesian methods. The aim of this paper was to present an efficient stochastic EM procedure, namely the SAEM algorithm, which is much faster to converge than the classical Monte Carlo EM algorithm and Bayesian estimation procedures, does not require specification of prior distributions and is quite robust to the choice of starting values. The key idea is to recycle the simulated values from one iteration to the next in the EM algorithm, which considerably accelerates the convergence. A simulation study is presented which confirms the advantages of this estimation procedure in the case of a genetic analysis. The SAEM algorithm was applied to real data sets on growth measurements in beef cattle and in chickens. The proposed estimation procedure, as the classical Monte Carlo EM algorithm, provides significance tests on the parameters and likelihood based model comparison criteria to compare the nonlinear models with other longitudinal methods. genetic analysis / growth curves / longitudinal data / stochastic approximation EM algorithm
Nonlinear mixed-effects models are very useful to analyze repeated measures data and are used in ... more Nonlinear mixed-effects models are very useful to analyze repeated measures data and are used in a variety of applications. Normal distributions for random effects and residual errors are usually assumed, but such assumptions make inferences vulnerable to the presence of outliers. In this work, we introduce an extension of a normal nonlinear mixed-effects model considering a subclass of elliptical contoured distributions for both random effects and residual errors. This elliptical subclass, the scale mixtures of normal (SMN) distributions, includes heavy-tailed multivariate distributions, such as Student-t, the contaminated normal and slash, among others, and represents an interesting alternative to outliers accommodation maintaining the elegance and simplicity of the maximum likelihood theory. We propose an exact estimation procedure to obtain the maximum likelihood estimates of the fixed-effects and variance components, using a stochastic approximation of the EM algorithm. We compare the performance of the normal and the SMN models with two real data sets.
The EM algorithm and its extensions are very popular tools for maximum likelihood estimation in i... more The EM algorithm and its extensions are very popular tools for maximum likelihood estimation in incomplete data setting. However, one of the limitations of these methods is their slow convergence. The PX-EM (parameter-expanded EM) algorithm was proposed by Liu, Rubin and Wu to make EM much faster. On the other hand, stochastic versions of EM are powerful alternatives of EM when the E-step is untractable in a closed form. In this paper we propose the PX-SAEM which is a parameter expansion version of the so-called SAEM (Stochastic Approximation version of EM). PX-SAEM is shown to accelerate SAEM and improve convergence toward the maximum likelihood estimate in a parametric framework. Numerical examples illustrate the behavior of PX-SAEM in linear and nonlinear mixed effects models.
The analysis of nonlinear function-valued characters is very important in genetic studies, especi... more The analysis of nonlinear function-valued characters is very important in genetic studies, especially for growth traits of agricultural and laboratory species. Inference in nonlinear mixed effects models is, however, quite complex and is usually based on likelihood approximations or Bayesian methods. The aim of this paper was to present an efficient stochastic EM procedure, namely the SAEM algorithm, which is much faster to converge than the classical Monte Carlo EM algorithm and Bayesian estimation procedures, does not require specification of prior distributions and is quite robust to the choice of starting values. The key idea is to recycle the simulated values from one iteration to the next in the EM algorithm, which considerably accelerates the convergence. A simulation study is presented which confirms the advantages of this estimation procedure in the case of a genetic analysis. The SAEM algorithm was applied to real data sets on growth measurements in beef cattle and in chickens. The proposed estimation procedure, as the classical Monte Carlo EM algorithm, provides significance tests on the parameters and likelihood based model comparison criteria to compare the nonlinear models with other longitudinal methods. genetic analysis / growth curves / longitudinal data / stochastic approximation EM algorithm
Generalized linear mixed models (GLMM) form a very general class of random effects models for dis... more Generalized linear mixed models (GLMM) form a very general class of random effects models for discrete and continuous responses in the exponential family. They are useful in a variety of applications. The traditional likelihood approach for GLMM usually involves high dimensional integrations which are computationally intensive. In this work, we investigate the case of binary outcomes analyzed under a two stage probit normal model with random effects. First, it is showed how ML estimates of the fixed effects and variance components can be computed using a stochastic approximation of the EM algorithm (SAEM). The SAEM algorithm can be applied directly, or in conjunction with a parameter expansion version of EM to speed up the convergence. A procedure is also proposed to obtain REML estimates of variance components and REML-based estimates of fixed effects. Finally an application to a real data set involving a clinical trial is presented in which these techniques are compared to other procedures (PQL, ML, Bayes) already available in classical softwares (SAS Glimmix, SAS Nlmixed, WinBUGS).
The analysis of nonlinear function-valued characters is very important in genetic studies, especi... more The analysis of nonlinear function-valued characters is very important in genetic studies, especially for growth traits of agricultural and laboratory species. Inference in nonlinear mixed effects models is, however, quite complex and is usually based on likelihood approximations or Bayesian methods. The aim of this paper was to present an efficient stochastic EM procedure, namely the SAEM algorithm, which is much faster to converge than the classical Monte Carlo EM algorithm and Bayesian estimation procedures, does not require specification of prior distributions and is quite robust to the choice of starting values. The key idea is to recycle the simulated values from one iteration to the next in the EM algorithm, which considerably accelerates the convergence. A simulation study is presented which confirms the advantages of this estimation procedure in the case of a genetic analysis. The SAEM algorithm was applied to real data sets on growth measurements in beef cattle and in chickens. The proposed estimation procedure, as the classical Monte Carlo EM algorithm, provides significance tests on the parameters and likelihood based model comparison criteria to compare the nonlinear models with other longitudinal methods. genetic analysis / growth curves / longitudinal data / stochastic approximation EM algorithm
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Papers by Cristian Meza