A Numerical Study of PQL Estimation Biases in Generalized Linear Mixed Models Under Heterogeneity of Random Effects

The penalized quasi-likelihood (PQL) approach is the most common estimation procedure for the generalized linear mixed model (GLMM). However, it has been noticed that the PQL tends to underestimate variance components as well as regression coefficients in the previous literature. In this article, we numerically show that the biases of variance component estimates by PQL are systematically related to the biases of regression coefficient estimates by PQL, and also show that the biases of variance component estimates by PQL increase as random effects become more heterogeneous.     

Penalized semiparametric density estimation

In this article we propose a penalized likelihood approach for the semiparametric density model with parametric and nonparametric components. An efficient iterative procedure is proposed for estimation. Approximate generalized maximum likelihood criterion from Bayesian point of view is derived for selecting the smoothing parameter. The finite sample performance of the proposed estimation approach is evaluated through simulation. Two real data examples, suicide study data and Old Faithful geyser data, are analyzed to demonstrate use of the proposed method.     

Schwarz Method for Penalized Quasi-Likelihood in Generalized Additive Models

The topic is penalized quasi-maximum likelihood estimation in generalized additive models by an approximation using a sequence of sub-models, here called blocks. The Schwarz method uses a sequence of sub-models, The technique might be useful to model comparison, where the fitted values from a sub-model are used as starting values for a larger model.

We show that the algorithm method converges in canonical link of generalized additive models, and a theorem about bound condition of sub-models convergence with uncanonical link.     

Estimating the variance for heterogeneity in arm‐based network meta‐analysis

Network meta‐analysis can be implemented by using arm‐based or contrast‐based models. Here we focus on arm‐based models and fit them using generalized linear mixed model procedures. Full maximum likelihood (ML) estimation leads to biased trial‐by‐treatment interaction variance estimates for heterogeneity. Thus, our objective is to investigate alternative approaches to variance estimation that reduce bias compared with full ML. Specifically, we use penalized quasi‐likelihood/pseudo‐likelihood and hierarchical (h) likelihood approaches. In addition, we consider a novel model modification that yields estimators akin to the residual maximum likelihood estimator for linear mixed models. The proposed methods are compared by simulation, and 2 real datasets are used for illustration. Simulations show that penalized quasi‐likelihood/pseudo‐likelihood and h‐likelihood reduce bias and yield satisfactory coverage rates. Sum‐to‐zero restriction and baseline contrasts for random trial‐by‐treatment interaction effects, as well as a residual ML‐like adjustment, also reduce bias compared with an unconstrained model when ML is used, but coverage rates are not quite as good. Penalized quasi‐likelihood/pseudo‐likelihood and h‐likelihood are therefore recommended.     

Optimal design for quasi-likelihood estimation in Poisson regression with random coefficients

Count data may be described by a Poisson regression model. If random coefficients are involved, maximum likelihood is not feasible and alternative estimation methods have to be employed. For the approach based on quasi-likelihood estimation a characterization of design optimality is derived and optimal designs are determined numerically for an example with random slope parameters.     

The Use of Working Variables in the Bayesian Modeling of Mean and Dispersion Parameters in Generalized Nonlinear Models with Random Effects

This article is aimed at reviewing a novel Bayesian approach to handle inference and estimation in the class of generalized nonlinear models. These models include some of the main techniques of statistical methodology, namely generalized linear models and parametric nonlinear regression. In addition, this proposal extends to methods for the systematic treatment of variation that is not explicitly predicted within the model, through the inclusion of random effects, and takes into account the modeling of dispersion parameters in the class of two-parameter exponential family. The methodology is based on the implementation of a two-stage algorithm that induces a hybrid approach based on numerical methods for approximating the likelihood to a normal density using a Taylor linearization around the values of current parameters in an MCMC routine.     

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.     

Maximum penalized likelihood estimation of mixed proportional hazard models

Unobservable individual effects in models of duration will cause estimation bias that include the structural parameters as well as the duration dependence. The maximum penalized likelihood estimator is examined as an estimator for the survivor model with heterogeneity. Proofs of the existence and uniqueness of the maximum penalized likelihood estimator in duration model with general forms of unobserved heterogeneity are provided. Some small sample evidence on the behavior of the maximum penalized likelihood estimator is given. The maximum penalized likelihood estimator is shown to be computationally feasible and to provide reasonable estimates in most cases.     

Shrinkage tuning parameter selection in precision matrices estimation

Recent literature provides many computational and modeling approaches for covariance matrices estimation in a penalized Gaussian graphical models but relatively little study has been carried out on the choice of the tuning parameter. This paper tries to fill this gap by focusing on the problem of shrinkage parameter selection when estimating sparse precision matrices using the penalized likelihood approach. Previous approaches typically used K-fold cross-validation in this regard. In this paper, we first derived the generalized approximate cross-validation for tuning parameter selection which is not only a more computationally efficient alternative, but also achieves smaller error rate for model fitting compared to leave-one-out cross-validation. For consistency in the selection of nonzero entries in the precision matrix, we employ a Bayesian information criterion which provably can identify the nonzero conditional correlations in the Gaussian model. Our simulations demonstrate the general superiority of the two proposed selectors in comparison with leave-one-out cross-validation, 10-fold cross-validation and Akaike information criterion.     

Sparse cluster analysis of large-scale discrete variables with application to single nucleotide polymorphism data

Currently, extreme large-scale genetic data present significant challenges for cluster analysis. Most of the existing clustering methods are typically built on the Euclidean distance and geared toward analyzing continuous response. They work well for clustering, e.g. microarray gene expression data, but often perform poorly for clustering, e.g. large-scale single nucleotide polymorphism (SNP) data. In this paper, we study the penalized latent class model for clustering extremely large-scale discrete data. The penalized latent class model takes into account the discrete nature of the response using appropriate generalized linear models and adopts the lasso penalized likelihood approach for simultaneous model estimation and selection of important covariates. We develop very efficient numerical algorithms for model estimation based on the iterative coordinate descent approach and further develop the expectation–maximization algorithm to incorporate and model missing values. We use simulation studies and applications to the international HapMap SNP data to illustrate the competitive performance of the penalized latent class model.     

Penalized Empirical Likelihood via Bridge Estimator in Cox's Proportional Hazard Model

We propose the penalized empirical likelihood method via bridge estimator in Cox's proportional hazard model for parameter estimation and variable selection. Under reasonable conditions, we show that penalized empirical likelihood in Cox's proportional hazard model has oracle property. A penalized empirical likelihood ratio for the vector of regression coefficients is defined and its limiting distribution is a chi-square distributions. The advantage of penalized empirical likelihood as a nonparametric likelihood approach is illustrated in testing hypothesis and constructing confidence sets. The method is illustrated by extensive simulation studies and a real example.     

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.     

Design considerations for small experiments and simple logistic regression

Inference for a generalized linear model is generally performed using asymptotic approximations for the bias and the covariance matrix of the parameter estimators. For small experiments, these approximations can be poor and result in estimators with considerable bias. We investigate the properties of designs for small experiments when the response is described by a simple logistic regression model and parameter estimators are to be obtained by the maximum penalized likelihood method of Firth [Firth, D., 1993, Bias reduction of maximum likelihood estimates. Biometrika, 80, 27–38]. Although this method achieves a reduction in bias, we illustrate that the remaining bias may be substantial for small experiments, and propose minimization of the integrated mean square error, based on Firth's estimates, as a suitable criterion for design selection. This approach is used to find locally optimal designs for two support points.     

Monte Carlo approximation of likelihood function in spatial GLMMs through an empirical Bayes method

In spatial generalized linear mixed models (SGLMMs), statistical inference encounters problems, since random effects in the model imply high-dimensional integrals to calculate the marginal likelihood function. In this article, we temporarily treat parameters as random variables and express the marginal likelihood function as a posterior expectation. Hence, the marginal likelihood function is approximated using the obtained samples from the posterior density of the latent variables and parameters given the data. However, in this setting, misspecification of prior distribution of correlation function parameter and problems associated with convergence of Markov chain Monte Carlo (MCMC) methods could have an unpleasant influence on the likelihood approximation. To avoid these challenges, we utilize an empirical Bayes approach to estimate prior hyperparameters. We also use a computationally efficient hybrid algorithm by combining inverse Bayes formula (IBF) and Gibbs sampler procedures. A simulation study is conducted to assess the performance of our method. Finally, we illustrate the method applying a dataset of standard penetration test of soil in an area in south of Iran.     

Latent Variable Models in Heterogeneous Spaces for Observations of Mixed Types

The maximum likelihood approach to the estimation of factor analytic model parameters most commonly deals with outcomes that are assumed to be multivariate Gaussian random variables in a homogeneous input space. In many practical settings, however, many studies needing factor analytic modeling involve data that, not only are not multivariate Gaussian variables, but also come from a partitioned input space. This article introduces an extension of the maximum likelihood factor analysis that handles multivariate outcomes made up of attributes with different probability distributions, and originating from a partitioned input space. An EM Algorithm combined with Fisher Scoring is used to estimate the parameters of the derived model.     

Penalized likelihood ratio test for a biomarker threshold effect in clinical trials based on generalized linear models

In a clinical trial, the responses to the new treatment may vary among patient subsets with different characteristics in a biomarker. It is often necessary to examine whether there is a cutpoint for the biomarker that divides the patients into two subsets of those with more favourable and less favourable responses. More generally, we approach this problem as a test of homogeneity in the effects of a set of covariates in generalized linear regression models. The unknown cutpoint results in a model with nonidentifiability and a nonsmooth likelihood function to which the ordinary likelihood methods do not apply. We first use a smooth continuous function to approximate the indicator function defining the patient subsets. We then propose a penalized likelihood ratio test to overcome the model irregularities. Under the null hypothesis, we prove that the asymptotic distribution of the proposed test statistic is a mixture of chi-squared distributions. Our method is based on established asymptotic theory, is simple to use, and works in a general framework that includes logistic, Poisson, and linear regression models. In extensive simulation studies, we find that the proposed test works well in terms of size and power. We further demonstrate the use of the proposed method by applying it to clinical trial data from the Digitalis Investigation Group (DIG) on heart failure.     

Generalized varying-coefficient single-index model

In this paper, the generalized varying-coefficient single-index model is discussed based on penalized likelihood. All the unknown functions are fitted by penalized spline. The estimates of the unknown parameters and the unknown coefficient functions are obtained and the estimation approach is rapid and computationally stable. Under some mild conditions, the consistency and the asymptotic normality of these resulting estimators are given. Two simulation studies are carried out to illustrate the performance of the estimates. An application of the model to the Hong Kong environmental data further demonstrates the potential of the proposed modelling procedures.     

An evaluation of ridge estimator in linear mixed models: an example from kidney failure data

This paper is concerned with the ridge estimation of fixed and random effects in the context of Henderson's mixed model equations in the linear mixed model. For this purpose, a penalized likelihood method is proposed. A linear combination of ridge estimator for fixed and random effects is compared to a linear combination of best linear unbiased estimator for fixed and random effects under the mean-square error (MSE) matrix criterion. Additionally, for choosing the biasing parameter, a method of MSE under the ridge estimator is given. A real data analysis is provided to illustrate the theoretical results and a simulation study is conducted to characterize the performance of ridge and best linear unbiased estimators approach in the linear mixed model.     

Two Adjusted Empirical-Likelihood-Based Methods in Generalized Varying-Coefficient Partially Linear Model

An empirical likelihood method was proposed by Owen and has been extended to many semiparametric and nonparametric models with a continuous response variable. However, there has been less attention focused on the generalized regression model. This article systematically studies two adjusted empirical-likelihood-based methods in the generalized varying-coefficient partially linear models. Based on the popular profile likelihood estimation procedure, the new adjusted empirical likelihood technology for the parameter is established and the resulting statistics are shown to be asymptotically standard chi-square distributed. Further, the adjusted empirical-likelihood-based confidence regions are established, and an efficient adjusted profile empirical-likelihood-based confidence intervals/regions for any components of the parameter, which are of primary interest, is also constructed. Their asymptotic properties are also derived. Some numerical studies are carried out to illustrate the performance of the proposed inference procedures.