Likelihood Inference for Spatial Generalized Linear Mixed Models

Spatial modeling is widely used in environmental sciences, biology, and epidemiology. Generalized linear mixed models are employed to account for spatial variations of point-referenced data called spatial generalized linear mixed models (SGLMMs). Frequentist analysis of these type of data is computationally difficult. On the other hand, the advent of the Markov chain Monte Carlo algorithm has made the Bayesian analysis of SGLMM computationally convenient. Recent introduction of the method of data cloning, which leads to maximum likelihood estimate, has made frequentist analysis of mixed models also equally computationally convenient. Recently, the data cloning was employed to estimate model parameters in SGLMMs, however, the prediction of spatial random effects and kriging are also very important. In this article, we propose a frequentist approach based on data cloning to predict (and provide prediction intervals) spatial random effects and kriging. We illustrate this approach using a real dataset and also by a simulation study.     

Variable selection for generalized linear mixed models by L 1-penalized estimation

Generalized linear mixed models are a widely used tool for modeling longitudinal data. However, their use is typically restricted to few covariates, because the presence of many predictors yields unstable estimates. The presented approach to the fitting of generalized linear mixed models includes an L ₁-penalty term that enforces variable selection and shrinkage simultaneously. A gradient ascent algorithm is proposed that allows to maximize the penalized log-likelihood yielding models with reduced complexity. In contrast to common procedures it can be used in high-dimensional settings where a large number of potentially influential explanatory variables is available. The method is investigated in simulation studies and illustrated by use of real data sets.     

Analyzing Binomial Data in a Split-Plot Design: Classical Approach or Modern Techniques?

Modeling data that are non-normally distributed with random effects is the major challenge in analyzing binomial data in split-plot designs. Seven methods for analyzing such data using mixed, generalized linear, or generalized linear mixed models are compared for the size and power of the tests. This study shows that analyzing random effects properly is more important than adjusting the analysis for non-normality. Methods based on mixed and generalized linear mixed models hold Type I error rates better than generalized linear models. Mixed model methods tend to have higher power than generalized linear mixed models when the sample size is small.     

A diagnostic of influential cases based on the information complexity criteria in generalized linear mixed models

ABSTRACT

Modeling diagnostics assess models by means of a variety of criteria. Each criterion typically performs its evaluation upon a specific inferential objective. For instance, the well-known DFBETAS in linear regression models are a modeling diagnostic which is applied to discover the influential cases in fitting a model. To facilitate the evaluation of generalized linear mixed models (GLMM), we develop a diagnostic for detecting influential cases based on the information complexity (ICOMP) criteria for detecting influential cases which substantially affect the model selection criterion ICOMP. In a given model, the diagnostic compares the ICOMP criterion between the full data set and a case-deleted data set. The computational formula of the ICOMP criterion is evaluated using the Fisher information matrix. A simulation study is accomplished and a real data set of cancer cells is analyzed using the logistic linear mixed model for illustrating the effectiveness of the proposed diagnostic in detecting the influential cases.     

Estimated estimating equations: semiparametric inference for clustered and longitudinal data

Summary.  We introduce a flexible marginal modelling approach for statistical inference for clustered and longitudinal data under minimal assumptions. This estimated estimating equations approach is semiparametric and the proposed models are fitted by quasi-likelihood regression, where the unknown marginal means are a function of the fixed effects linear predictor with unknown smooth link, and variance–covariance is an unknown smooth function of the marginal means. We propose to estimate the nonparametric link and variance–covariance functions via smoothing methods, whereas the regression parameters are obtained via the estimated estimating equations. These are score equations that contain nonparametric function estimates. The proposed estimated estimating equations approach is motivated by its flexibility and easy implementation. Moreover, if data follow a generalized linear mixed model, with either a specified or an unspecified distribution of random effects and link function, the model proposed emerges as the corresponding marginal (population-average) version and can be used to obtain inference for the fixed effects in the underlying generalized linear mixed model, without the need to specify any other components of this generalized linear mixed model. Among marginal models, the estimated estimating equations approach provides a flexible alternative to modelling with generalized estimating equations. Applications of estimated estimating equations include diagnostics and link selection. The asymptotic distribution of the proposed estimators for the model parameters is derived, enabling statistical inference. Practical illustrations include Poisson modelling of repeated epileptic seizure counts and simulations for clustered binomial responses.     

Mixed effects smoothing spline analysis of variance

We propose a general family of nonparametric mixed effects models. Smoothing splines are used to model the fixed effects and are estimated by maximizing the penalized likelihood function. The random effects are generic and are modelled parametrically by assuming that the covariance function depends on a parsimonious set of parameters. These parameters and the smoothing parameter are estimated simultaneously by the generalized maximum likelihood method. We derive a connection between a nonparametric mixed effects model and a linear mixed effects model. This connection suggests a way of fitting a nonparametric mixed effects model by using existing programs. The classical two-way mixed models and growth curve models are used as examples to demonstrate how to use smoothing spline analysis-of-variance decompositions to build nonparametric mixed effects models. Similarly to the classical analysis of variance, components of these nonparametric mixed effects models can be interpreted as main effects and interactions. The penalized likelihood estimates of the fixed effects in a two-way mixed model are extensions of James–Stein shrinkage estimates to correlated observations. In an example three nested nonparametric mixed effects models are fitted to a longitudinal data set.     

Mixture of linear mixed models using multivariate t distribution

Linear mixed models are widely used when multiple correlated measurements are made on each unit of interest. In many applications, the units may form several distinct clusters, and such heterogeneity can be more appropriately modelled by a finite mixture linear mixed model. The classical estimation approach, in which both the random effects and the error parts are assumed to follow normal distribution, is sensitive to outliers, and failure to accommodate outliers may greatly jeopardize the model estimation and inference. We propose a new mixture linear mixed model using multivariate t distribution. For each mixture component, we assume the response and the random effects jointly follow a multivariate t distribution, to conveniently robustify the estimation procedure. An efficient expectation conditional maximization algorithm is developed for conducting maximum likelihood estimation. The degrees of freedom parameters of the t distributions are chosen data adaptively, for achieving flexible trade-off between estimation robustness and efficiency. Simulation studies and an application on analysing lung growth longitudinal data showcase the efficacy of the proposed approach.     

Estimation of regression vectors in linear mixed models with Dirichlet process random effects

The Dirichlet process has been used extensively in Bayesian non parametric modeling, and has proven to be very useful. In particular, mixed models with Dirichlet process random effects have been used in modeling many types of data and can often outperform their normal random effect counterparts. Here we examine the linear mixed model with Dirichlet process random effects from a classical view, and derive the best linear unbiased estimator (BLUE) of the fixed effects. We are also able to calculate the resulting covariance matrix and find that the covariance is directly related to the precision parameter of the Dirichlet process, giving a new interpretation of this parameter. We also characterize the relationship between the BLUE and the ordinary least-squares (OLS) estimator and show how confidence intervals can be approximated.     

Fairness of the national health service in Italy: a bivariate correlated random effects model

The primary purpose of this paper is to comprehensively assess households’ burden due to health payments. Starting from the fairness approach developed by the World Health Organization, we analyse the burden of healthcare payments on Italian households by modeling catastrophic payments and impoverishment due to healthcare expenditures. For this purpose, we propose to extend the analysis of fairness in financing contribution through a generalized linear mixed models by introducing a bivariate correlated random effects model, where association between the outcomes is modeled through individual- and outcome-specific latent effects which are assumed to be correlated. We discuss model parameter estimation in a finite mixture context. By using such model specification, the fairness of the Italian national health service is investigated.     

Measuring the complexity of generalized linear hierarchical models

Measuring a statistical model's complexity is important for model criticism and comparison. However, it is unclear how to do this for hierarchical models due to uncertainty about how to count the random effects. The authors develop a complexity measure for generalized linear hierarchical models based on linear model theory. They demonstrate the new measure for binomial and Poisson observables modeled using various hierarchical structures, including a longitudinal model and an areal‐data model having both spatial clustering and pure heterogeneity random effects. They compare their new measure to a Bayesian index of model complexity, the effective number p_D of parameters (Spiegelhalter, Best, Carlin & van der Linde 2002); the comparisons are made in the binomial and Poisson cases via simulation and two real data examples. The two measures are usually close, but differ markedly in some instances where p_D is arguably inappropriate. Finally, the authors show how the new measure can be used to approach the difficult task of specifying prior distributions for variance components, and in the process cast further doubt on the commonly‐used vague inverse gamma prior.     

A mixture latent variable model for modeling mixed data in heterogeneous populations and its applications

Latent variable models are widely used for jointly modeling of mixed data including nominal, ordinal, count and continuous data. In this paper, we consider a latent variable model for jointly modeling relationships between mixed binary, count and continuous variables with some observed covariates. We assume that, given a latent variable, mixed variables of interest are independent and count and continuous variables have Poisson distribution and normal distribution, respectively. As such data may be extracted from different subpopulations, consideration of an unobserved heterogeneity has to be taken into account. A mixture distribution is considered (for the distribution of the latent variable) which accounts the heterogeneity. The generalized EM algorithm which uses the Newton–Raphson algorithm inside the EM algorithm is used to compute the maximum likelihood estimates of parameters. The standard errors of the maximum likelihood estimates are computed by using the supplemented EM algorithm. Analysis of the primary biliary cirrhosis data is presented as an application of the proposed model.     

Estimation of the Force of Infection from Current Status Data Using Generalized Linear Mixed Models

Based on sero-prevalence data of rubella, mumps in the UK and varicella in Belgium, we show how the force of infection, the age-specific rate at which susceptible individuals contract infection, can be estimated using generalized linear mixed models (McCulloch & Searle, 2001). Modelling the dependency of the force of infection on age by penalized splines, which involve fixed and random effects, allows us to use generalized linear mixed models techniques to estimate both the cumulative probability of being infected before a given age and the force of infection. Moreover, these models permit an automatic selection of the smoothing parameter. The smoothness of the estimated force of infection can be influenced by the number of knots and the degree of the penalized spline used. To determine these, a different number of knots and different degrees are used and the results are compared to establish this sensitivity. Simulations with a different number of knots and polynomial spline bases of different degrees suggest - for estimating the force of infection from serological data - the use of a quadratic penalized spline based on about 10 knots.     

Prediction of transplant-free survival in idiopathic pulmonary fibrosis patients using joint models for event times and mixed multivariate longitudinal data

We implement a joint model for mixed multivariate longitudinal measurements, applied to the prediction of time until lung transplant or death in idiopathic pulmonary fibrosis. Specifically, we formulate a unified Bayesian joint model for the mixed longitudinal responses and time-to-event outcomes. For the longitudinal model of continuous and binary responses, we investigate multivariate generalized linear mixed models using shared random effects. Longitudinal and time-to-event data are assumed to be independent conditional on available covariates and shared parameters. A Markov chain Monte Carlo algorithm, implemented in OpenBUGS, is used for parameter estimation. To illustrate practical considerations in choosing a final model, we fit 37 different candidate models using all possible combinations of random effects and employ a deviance information criterion to select a best-fitting model. We demonstrate the prediction of future event probabilities within a fixed time interval for patients utilizing baseline data, post-baseline longitudinal responses, and the time-to-event outcome. The performance of our joint model is also evaluated in simulation studies.     

Statistical inferences for partially linear single-index models with error-prone linear covariates

We consider statistical inference for partially linear single-index models (PLSIM) when some linear covariates are not observed, but ancillary variables are available. Based on the profile least-squared estimators of the unknowns, we study the testing problems for parametric components in the proposed models. It is to see whether the generalized likelihood ratio (GLR) tests proposed by Fan et al. (2001) are applicable to testing for the parametric components. We show that under the null hypothesis the proposed GLR statistics follow asymptotically the χ²-distributions with the scale constants and the degrees of freedom being independent of the nuisance parameters or functions, which is called the Wilks phenomenon. Simulated experiments are conducted to illustrate our proposed methodology.     

An Alternative Estimation Approach for the Heterogeneity Linear Mixed Model

In this article, an alternative estimation approach is proposed to fit linear mixed effects models where the random effects follow a finite mixture of normal distributions. This heterogeneity linear mixed model is an interesting tool since it relaxes the classical normality assumption and is also perfectly suitable for classification purposes, based on longitudinal profiles. Instead of fitting directly the heterogeneity linear mixed model, we propose to fit an equivalent mixture of linear mixed models under some restrictions which is computationally simpler. Unlike the former model, the latter can be maximized analytically using an EM-algorithm and the obtained parameter estimates can be easily used to compute the parameter estimates of interest.     

Joint modeling of bottle use,daily milk intake from bottles,and daily energy intake in toddlers

The current study follows an educational intervention on bottle-weaning to simultaneously evaluate effects of the bottle-weaning intervention on reducing bottle use, daily milk intake from bottles, and daily energy intake in toddlers aged 11–13 months. In this paper, we propose to use shared parameter models and random effects models to model these outcomes jointly. Our joint models consist of two submodels: a two-part submodel for modeling the odds of bottle use and the intensity of daily milk intake from bottles, and a linear mixed submodel for modeling the intensity of daily energy intake. The two submodels are linked by either shared random effects or separate but correlated random effects. We investigate whether the intervention effects, parameter estimates, and model fit differ between shared parameter models and random effects models.     

Residuals and leverages in the linear mixed measurement error models

Residuals are frequently used to evaluate the validity of the assumptions of statistical models and may also be employed as tools for model selection. In this paper, we consider residuals and their limiting properties in the linear mixed measurement error models. Also, we develop types of residuals for these models and then review some of the residual analysis techniques. Further, by using the definition of generalized leverage, we derive generalized leverage matrices for identification of high-leverage points for these models. Finally, we analyse a real data set.     

Clustering gene expression time course data using mixtures of multivariate t-distributions

Clustering gene expression time course data is an important problem in bioinformatics because understanding which genes behave similarly can lead to the discovery of important biological information. Statistically, the problem of clustering time course data is a special case of the more general problem of clustering longitudinal data. In this paper, a very general and flexible model-based technique is used to cluster longitudinal data. Mixtures of multivariate t-distributions are utilized, with a linear model for the mean and a modified Cholesky-decomposed covariance structure. Constraints are placed upon the covariance structure, leading to a novel family of mixture models, including parsimonious models. In addition to model-based clustering, these models are also used for model-based classification, i.e., semi-supervised clustering. Parameters, including the component degrees of freedom, are estimated using an expectation-maximization algorithm and two different approaches to model selection are considered. The models are applied to simulated data to illustrate their efficacy; this includes a comparison with their Gaussian analogues—the use of these Gaussian analogues with a linear model for the mean is novel in itself. Our family of multivariate t mixture models is then applied to two real gene expression time course data sets and the results are discussed. We conclude with a summary, suggestions for future work, and a discussion about constraining the degrees of freedom parameter.