A new test for random effects in linear mixed models with longitudinal data

As it is known, testing the existence of random effects is often transferred to testing their zero variances/covariance matrices. It is a nonstandard testing problem because the hypothetical values are on the boundary of the whole space. In the literature, a difference-based test was proposed, which has asymptotically tractable null distribution and is then easy to implement. However, the projection method on which the difference-based test relies may affect and deteriorate its performance when covariates associated with fixed effects and covariates associated with random effects are highly correlated. In the paper, for linear mixed models (LMM) with longitudinal data, a new test is proposed to avoid this problem. The new test is also asymptotically distribution-free and more powerful than the difference-based test, particularly when the above correlation is high. The new test is consistent against all global alternatives and can detect local alternatives converging to the null at a rate as close as to m^−1/2$m^{-1/2}$ with m being the number of subjects. Simulations are carried out to examine the performance and a real data analysis is performed for illustration.     

Checking identifiability of covariance parameters in linear mixed effects models

To build a linear mixed effects model, one needs to specify the random effects and often the associated parametrized covariance matrix structure. Inappropriate specification of the structures can result in the covariance parameters of the model not identifiable. Non-identifiability can result in extraordinary wide confidence intervals, and unreliable parameter inference. Sometimes software produces implication of model non-identifiability, but not always. In the simulation of fitting non-identifiable models we tried, about half of the times the software output did not look abnormal. We derive necessary and sufficient conditions of covariance parameters identifiability which does not require any prior model fitting. The results are easy to implement and are applicable to commonly used covariance matrix structures.     

Reference priors for linear models with general covariance structures

We develop a new class of reference priors for linear models with general covariance structures. A general Markov chain Monte Carlo algorithm is also proposed for implementing the computation. We present several examples to demonstrate the results: Bayesian penalized spline smoothing, a Bayesian approach to bivariate smoothing for a spatial model, and prior specification for structural equation models.     

Robust designs for linear mixed effects models

Summary.  In health sciences, medicine and social sciences linear mixed effects models are often used to analyse time-structured data. The search for optimal designs for these models is often hampered by two problems. The first problem is that these designs are only locally optimal. The second problem is that an optimal design for one model may not be optimal for other models. In this paper the maximin principle is adopted to handle both problems, simultaneously. The maximin criterion is formulated by means of a relative efficiency measure, which gives an indication of how much efficiency is lost when the uncertainty about the models over a prior domain of parameters is taken into account. The procedure is illustrated by means of three growth studies. Results are presented for a vocabulary growth study from education, a bone gain study from medical research and an epidemiological decline in height study. It is shown that, for the mixed effects polynomial models that are applied to these studies, the maximin designs remain highly efficient for different sets of models and combinations of parameter values.     

Bayesian parsimonious covariance estimation for hierarchical linear mixed models

We consider a non-centered parameterization of the standard random-effects model, which is based on the Cholesky decomposition of the variance-covariance matrix. The regression type structure of the non-centered parameterization allows us to use Bayesian variable selection methods for covariance selection. We search for a parsimonious variance-covariance matrix by identifying the non-zero elements of the Cholesky factors. With this method we are able to learn from the data for each effect whether it is random or not, and whether covariances among random effects are zero. An application in marketing shows a substantial reduction of the number of free elements in the variance-covariance matrix.     

On nonlinear random effects models for repeated measurements

Linear random effects models for longitudinal data discussed by Laird and Ware (1982), Jennrich and Schluchter (1986), Lange and Laird (1989), and others are extended in a straight forward manner to nonlinear random effects models. This results in a simple computational approach which accommodates patterned covariance matrices and data insufficient for fitting each subject separately. The technique is demonstrated with an interesting medical data set, and a short, simple SAS PROC IML program based on the EM algorithm is presented.     

Diagnostics for elliptical linear mixed models with first-order autoregressive errors

For longitudinal time series data, linear mixed models that contain both random effects across individuals and first-order autoregressive errors within individuals may be appropriate. Some statistical diagnostics based on the models under a proposed elliptical error structure are developed in this work. It is well known that the class of elliptical distributions offers a more flexible framework for modelling since it contains both light- and heavy-tailed distributions. Iterative procedures for the maximum-likelihood estimates of the model parameters are presented. Score tests for the presence of autocorrelation and the homogeneity of autocorrelation coefficients among individuals are constructed. The properties of test statistics are investigated through Monte Carlo simulations. The local influence method for the models is also given. The analysed results of a real data set illustrate the values of the models and diagnostic statistics.     

On weak consistency in linear models with equi-correlated random errors

A new estimator in linear models with equi-correlated random errors is postulated. Consistency properties of the proposed estimator and the ordinary least squares estimator are studied. It is shown that the new estimator has smaller variance than the usual least squares estimator under some mild conditions. In addition, it is observed that the new estimator tends to be weakly consistent in many cases where the usual least squares estimator is not.     

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.     

Robust estimation of covariance parameters in partial linear model for longitudinal data

For longitudinal data, the within-subject dependence structure and covariance parameters may be of practical and theoretical interests. The estimation of covariance parameters has received much attention and been studied mainly in the framework of generalized estimating equations (GEEs). The GEEs method, however, is sensitive to outliers. In this paper, an alternative set of robust generalized estimating equations for both the mean and covariance parameters are proposed in the partial linear model for longitudinal data. The asymptotic properties of the proposed estimators of regression parameters, non-parametric function and covariance parameters are obtained. Simulation studies are conducted to evaluate the performance of the proposed estimators under different contaminations. The proposed method is illustrated with a real data analysis.     

Some factors affecting statistical power of approximate tests in the linear mixed model for longitudinal data

Different longitudinal study designs require different statistical analysis methods and different methods of sample size determination. Statistical power analysis is a flexible approach to sample size determination for longitudinal studies. However, different power analyses are required for different statistical tests which arises from the difference between different statistical methods. In this paper, the simulation-based power calculations of F-tests with Containment, Kenward-Roger or Satterthwaite approximation of degrees of freedom are examined for sample size determination in the context of a special case of linear mixed models (LMMs), which is frequently used in the analysis of longitudinal data. Essentially, the roles of some factors, such as variance–covariance structure of random effects [unstructured UN or factor analytic FA0], autocorrelation structure among errors over time [independent IND, first-order autoregressive AR1 or first-order moving average MA1], parameter estimation methods [maximum likelihood ML and restricted maximum likelihood REML] and iterative algorithms [ridge-stabilized Newton-Raphson and Quasi-Newton] on statistical power of approximate F-tests in the LMM are examined together, which has not been considered previously. The greatest factor affecting statistical power is found to be the variance–covariance structure of random effects in the LMM. It appears that the simulation-based analysis in this study gives an interesting insight into statistical power of approximate F-tests for fixed effects in LMMs for longitudinal data.     

A simultaneous variable selection methodology for linear mixed models

Selecting an appropriate structure for a linear mixed model serves as an appealing problem in a number of applications such as in the modelling of longitudinal or clustered data. In this paper, we propose a variable selection procedure for simultaneously selecting and estimating the fixed and random effects. More specifically, a profile log-likelihood function, along with an adaptive penalty, is utilized for sparse selection. The Newton-Raphson optimization algorithm is performed to complete the parameter estimation. By jointly selecting the fixed and random effects, the proposed approach increases selection accuracy compared with two-stage procedures, and the usage of the profile log-likelihood can improve computational efficiency in one-stage procedures. We prove that the proposed procedure enjoys the model selection consistency. A simulation study and a real data application are conducted for demonstrating the effectiveness of the proposed method.     

Selection of terms in random coefficient regression models

The selection of suitable terms in random coefficient regression models is a challenging problem to practitioners. Although many techniques, ranging from those with a theoretical flavour to those with an exploratory spirit, have been proposed for such purposes, no particular one may be considered as a paradigm. In fact, many authors advocate that they should be used in a complementary way. We consider exploratory methods based on fitting standard regression models to the individual response profiles or to the rows of the sample within-units covariance matrix (for balanced data) that may serve as additional tools in the process of selecting an appropriate model. We evaluate the performance of the proposal via a simulation study and consider applications to two examples in the field of Biostatistics.     

Generalized linear mixed models: a review and some extensions

Breslow and Clayton (J Am Stat Assoc 88:9–25,1993) was, and still is, a highly influential paper mobilizing the use of generalized linear mixed models in epidemiology and a wide variety of fields. An important aspect is the feasibility in implementation through the ready availability of related software in SAS (SAS Institute, PROC GLIMMIX, SAS Institute Inc., URL , 2007), S-plus (Insightful Corporation, S-PLUS 8, Insightful Corporation, Seattle, WA, URL , 2007), and R (R Development Core Team, R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing, Vienna, Austria, URL , 2006) for example, facilitating its broad usage. This paper reviews background to generalized linear mixed models and the inferential techniques which have been developed for them. To provide the reader with a flavor of the utility and wide applicability of this fundamental methodology we consider a few extensions including additive models, models for zero-heavy data, and models accommodating latent clusters.     

Bayesian model selection in linear mixed effects models with autoregressive(p) errors using mixture priors

In this article, we apply the Bayesian approach to the linear mixed effect models with autoregressive(p) random errors under mixture priors obtained with the Markov chain Monte Carlo (MCMC) method. The mixture structure of a point mass and continuous distribution can help to select the variables in fixed and random effects models from the posterior sample generated using the MCMC method. Bayesian prediction of future observations is also one of the major concerns. To get the best model, we consider the commonly used highest posterior probability model and the median posterior probability model. As a result, both criteria tend to be needed to choose the best model from the entire simulation study. In terms of predictive accuracy, a real example confirms that the proposed method provides accurate results.     

Leverage analysis for linear mixed models

We consider a generalized leverage matrix useful for the identification of influential units and observations in linear mixed models and show how a decomposition of this matrix may be employed to identify high leverage points for both the marginal fitted values and the random effect component of the conditional fitted values. We illustrate the different uses of the two components of the decomposition with a simulated example as well as with a real data set.     

Quasi-complete separation in random effects of binary response mixed models

ABSTRACT

Clustered observations such as longitudinal data are often analysed with generalized linear mixed models (GLMM). Approximate Bayesian inference for GLMMs with normally distributed random effects can be done using integrated nested Laplace approximations (INLA), which is in general known to yield accurate results. However, INLA is known to be less accurate for GLMMs with binary response. For longitudinal binary response data it is common that patients do not change their health state during the study period. In this case the grouping covariate perfectly predicts a subset of the response, which implies a monotone likelihood with diverging maximum likelihood (ML) estimates for cluster-specific parameters. This is known as quasi-complete separation. In this paper we demonstrate, based on longitudinal data from a randomized clinical trial and two simulations, that the accuracy of INLA decreases with increasing degree of cluster-specific quasi-complete separation. Comparing parameter estimates by INLA, Markov chain Monte Carlo sampling and ML shows that INLA increasingly deviates from the other methods in such a scenario.     

Bayesian covariance estimation and inference in latent Gaussian process models

This paper describes inference methods for functional data under the assumption that the functional data of interest are smooth latent functions, characterized by a Gaussian process, which have been observed with noise over a finite set of time points. The methods we propose are completely specified in a Bayesian environment that allows for all inferences to be performed through a simple Gibbs sampler. Our main focus is in estimating and describing uncertainty in the covariance function. However, these models also encompass functional data estimation, functional regression where the predictors are latent functions, and an automatic approach to smoothing parameter selection. Furthermore, these models require minimal assumptions on the data structure as the time points for observations do not need to be equally spaced, the number and placement of observations are allowed to vary among functions, and special treatment is not required when the number of functional observations is less than the dimensionality of those observations. We illustrate the effectiveness of these models in estimating latent functional data, capturing variation in the functional covariance estimate, and in selecting appropriate smoothing parameters in both a simulation study and a regression analysis of medfly fertility data.     

General class of covariance structures for two or more repeated factors in longitudinal data analysis

The main difficulty in parametric analysis of longitudinal data lies in specifying covariance structure. Several covariance structures, which usually reflect one series of measurements collected over time, have been presented in the literature. However there is a lack of literature on covariance structures designed for repeated measures specified by more than one repeated factor. In this paper a new, general method of modelling covariance structure based on the Kronecker product of underlying factor specific covariance profiles is presented. The method has an attractive interpretation in terms of independent factor specific contribution to overall within subject covariance structure and can be easily adapted to standard software.