A comparison study on modeling of clustered and overdispersed count data for multiple comparisons

Data collected in various scientific fields are count data. One way to analyze such data is to compare the individual levels of the factor treatment using multiple comparisons. However, the measured individuals are often clustered – e.g. according to litter or rearing. This must be considered when estimating the parameters by a repeated measurement model. In addition, ignoring the overdispersion to which count data is prone leads to an increase of the type one error rate. We carry out simulation studies using several different data settings and compare different multiple contrast tests with parameter estimates from generalized estimation equations and generalized linear mixed models in order to observe coverage and rejection probabilities. We generate overdispersed, clustered count data in small samples as can be observed in many biological settings. We have found that the generalized estimation equations outperform generalized linear mixed models if the variance-sandwich estimator is correctly specified. Furthermore, generalized linear mixed models show problems with the convergence rate under certain data settings, but there are model implementations with lower implications exists. Finally, we use an example of genetic data to demonstrate the application of the multiple contrast test and the problems of ignoring strong overdispersion.     

EXPONENTIAL DISPERSION MODELS AND THE GAUSS-NEWTON ALGORITHM

It is known that the Fisher scoring iteration for generalized linear models has the same form as the Gauss-Newton algorithm for normal regression. This note shows that exponential dispersion models are the most general families to preserve this form for the scoring iteration. Therefore exponential dispersion models are the most general extension of generalized linear models for which the analogy with normal regression is preserved. The multinomial distribution is used as an example.     

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.     

Estimation in large cross random-effect models by data augmentation

Estimation in mixed linear models is, in general, computationally demanding, since applied problems may involve extensive data sets and large numbers of random effects. Existing computer algorithms are slow and/or require large amounts of memory. These problems are compounded in generalized linear mixed models for categorical data, since even approximate methods involve fitting of a linear mixed model within steps of an iteratively reweighted least squares algorithm. Only in models in which the random effects are hierarchically nested can the computations for fitting these models to large data sets be carried out rapidly. We describe a data augmentation approach to these computational difficulties in which we repeatedly fit an overlapping series of submodels, incorporating the missing terms in each submodel as 'offsets'. The submodels are chosen so that they have a nested random-effect structure, thus allowing maximum exploitation of the computational efficiency which is available in this case. Examples of the use of the algorithm for both metric and discrete responses are discussed, all calculations being carried out using macros within the MLwiN program.     

On the use of between–within models to adjust for confounding due to unmeasured cluster-level covariates

Between–within models are generalized linear mixed models (GLMMs) for clustered data that incorporate a random intercept together with fixed effects for within-cluster and between-cluster covariates; the between-cluster covariates represent the cluster means of the within-cluster covariates. One popular use of these models is to adjust for confounding of the effect of within-cluster covariates due to unmeasured between-cluster covariates. Previous research has shown via simulations that using this approach can yield inconsistent estimators. We present theory and simulations as evidence that a primary cause of the inconsistency is heteroscedasticity of the linearized version of the GLMM used for estimation.     

Generalised additive mixed models analysis via gammSlice

We demonstrate the use of our R package, gammSlice, for Bayesian fitting and inference in generalised additive mixed model analysis. This class of models includes generalised linear mixed models and generalised additive models as special cases. Accurate Bayesian inference is achievable via sufficiently large Markov chain Monte Carlo (MCMC) samples. Slice sampling is a key component of the MCMC scheme. Comparisons with existing generalised additive mixed model software shows that gammSlice offers improved inferential accuracy, albeit at the cost of longer computational time.     

Robust quasi-likelihood inference in generalized linear mixed models with outliers

It is well known that in a traditional outlier-free situation, the generalized quasi-likelihood (GQL) approach [B.C. Sutradhar, On exact quasilikelihood inference in generalized linear mixed models, Sankhya: Indian J. Statist. 66 (2004), pp. 261–289] performs very well to obtain the consistent as well as the efficient estimates for the parameters involved in the generalized linear mixed models (GLMMs). In this paper, we first examine the effect of the presence of one or more outliers on the GQL estimation for the parameters in such GLMMs, especially in two important models such as count and binary mixed models. The outliers appear to cause serious biases and hence inconsistency in the estimation. As a remedy, we then propose a robust GQL (RGQL) approach in order to obtain the consistent estimates for the parameters in the GLMMs in the presence of one or more outliers. An extensive simulation study is conducted to examine the consistency performance of the proposed RGQL approach.     

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.     

广义线性混合模型在顾客满意度研究中的应用——基于某地区银行理财产品顾客满意度的分析

在对广义线性模型与经典线性模型进行对比分析基础上,重点介绍了广义线性混合模型与估计方法及其在满意度调查数据中的模型设定与应用,并采用某调查机构在2011年1月至2012年3月期间对购买过某地区银行理财产品的客户进行的满意度调查数据进行实证分析。研究表明:相对于经典线性回归模型与广义线性模型,广义线性混合模型是分析满意度调查数据的有效方法。     

Inference in generalized additive mixed modelsby using smoothing splines

Generalized additive mixed models are proposed for overdispersed and correlated data, which arise frequently in studies involving clustered, hierarchical and spatial designs. This class of models allows flexible functional dependence of an outcome variable on covariates by using nonparametric regression, while accounting for correlation between observations by using random effects. We estimate nonparametric functions by using smoothing splines and jointly estimate smoothing parameters and variance components by using marginal quasi-likelihood. Because numerical integration is often required by maximizing the objective functions, double penalized quasi-likelihood is proposed to make approximate inference. Frequentist and Bayesian inferences are compared. A key feature of the method proposed is that it allows us to make systematic inference on all model components within a unified parametric mixed model framework and can be easily implemented by fitting a working generalized linear mixed model by using existing statistical software. A bias correction procedure is also proposed to improve the performance of double penalized quasi-likelihood for sparse data. We illustrate the method with an application to infectious disease data and we evaluate its performance through simulation.     

Influence diagnostics in nonlinear reproductive dispersion mixed models

The class of nonlinear reproductive dispersion mixed models (NRDMMs) is an extension of nonlinear reproductive dispersion models and generalized linear mixed models. This paper discusses the influence analysis of the model based on Laplace approximation. The equivalence of case-deletion models and mean-shift outlier models in NRDMMs is investigated, and some diagnostic measures are proposed via the case-deletion method. We also investigate the assessment of local influence of various perturbation schemes. The proposed method is illustrated with an example.     

Longitudinal poisson regression with disturbed random intercept

Consider repeated event-count data from a sequence of exposures, during each of which a subject can experience some number of events, which is reported at ‘visits’ following each exposure. Within-subject heterogeneity not accounted for by visit-varying covariates is called ‘visit-level’ heterogeneity. Using generalized linear mixed models with log link for longitudinal Poisson regression, I model visit-level heterogeneity by cumulatively adding ‘disturbances’ to the random intercept of each subject over visits to create a ‘disturbed-random-intercept$rsquo; model. I also create a ‘disturbed-random-slope’ model, where the slope is over visits, and both intercept and slope are random but only the slope is disturbed. Simulation studies compare fixed-effect estimation for these models in data with 15 visits, large visit-level heterogeneity, and large multiplicative overdispersion. These studies show statistically significant superiority of the disturbed-random-intercept model. Examples with epidemiological data compare results of this model with those from other published models.     

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.     

A Simulation Comparison of Approximate Tests for Fixed Effects in Random Coefficients Growth Curve Models

Often, the response variables on sampling units are observed repeatedly over time. The sampling units may come from different populations, such as treatment groups. This setting is routinely modeled by a random coefficients growth curve model, and the techniques of general linear mixed models are applied to address the primary research aim. An alternative approach is to reduce each subject’s data to summary measures, such as within-subject averages or regression coefficients. One may then test for equality of means of the summary measures (or functions of them) among treatment groups. Here, we compare by simulation the performance characteristics of three approximate tests based on summary measures and one based on the full data, focusing mainly on accuracy of p-values. We find that performances of these procedures can be quite different for small samples in several different configurations of parameter values. The summary-measures approach performed at least as well as the full-data mixed models approach.     

Neutral umpires and leg before wicket decisions in test cricket

Summary.  The proportions of dismissals which were leg before wicket in test cricket matches during 1978–2004 are analysed by using generalized linear and mixed models to assess the effect of location, team and the presence or otherwise of neutral umpires. The location and the team batting are clearly significant. There is also clear evidence of an interaction showing that some teams' players are out leg before wicket less often at home but there is no further interaction with neutral umpires, suggesting that this is not caused simply by home umpires favouring the home team.     

Optimal cross-over designs for nonlinear mixed models using a first-order expansion

We consider the construction of optimal cross-over designs for nonlinear mixed effect models based on the first-order expansion. We show that for AB/BA designs a balanced subject allocation is optimal when the parameters depend on treatments only. For multiple period, multiple sequence designs, uniform designs are optimal among dual balanced designs under the same conditions. As a by-product, the same results hold for multivariate linear mixed models with variances depending on treatments.     

Estimation in Singular Linear Models with Stochastic Linear Restrictions

This article generalizes the ordinary mixed estimator (OME) in theory, and obtains the estimator of the unknown regression parameters in singular linear models with stochastic linear restrictions: singular mixed estimator (SME). We also give some properties of SME obtained in this article, and prove that it is superior to unrestricted least squared estimator (LSE) in singular linear models in the sense of the covariance matrix and generalized mean square error (GMSE). After that, we also have a discussion about the two-stage estimator of SME. The result we give in this article could be regarded as generalizations of both OME and unrestricted LSE at the same time.     

Estimating precision,repeatability, and reproducibility from Gaussian and non- Gaussian data: a mixed models approach

Quality control relies heavily on the use of formal assessment metrics. In this paper, for the context of veterinary epidemiology, we review the main proposals, precision, repeatability, reproducibility, and intermediate precision, in agreement with ISO (international Organization for Standardization) practice, generalize these by placing them within the linear mixed model framework, which we then extend to the generalized linear mixed model setting, so that both Gaussian as well as non-Gaussian data can be employed. Similarities and differences are discussed between the classical ANOVA (analysis of variance) approach and the proposed mixed model settings, on the one hand, and between the Gaussian and non-Gaussian cases, on the other hand. The new proposals are applied to five studies in three diseases: Aujeszky's disease, enzootic bovine leucosis (EBL) and bovine brucellosis. The mixed-models proposals are also discussed in the light of their computational requirements.     

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.     

A Robust Variable Selection to t-type Joint Generalized Linear Models via Penalized t-type Pseudo-likelihood

Although the t-type estimator is a kind of M-estimator with scale optimization, it has some advantages over the M-estimator. In this article, we first propose a t-type joint generalized linear model as a robust extension to the classical joint generalized linear models for modeling data containing extreme or outlying observations. Next, we develop a t-type pseudo-likelihood (TPL) approach, which can be viewed as a robust version to the existing pseudo-likelihood (PL) approach. To determine which variables significantly affect the variance of the response variable, we then propose a unified penalized maximum TPL method to simultaneously select significant variables for the mean and dispersion models in t-type joint generalized linear models. Thus, the proposed variable selection method can simultaneously perform parameter estimation and variable selection in the mean and dispersion models. With appropriate selection of the tuning parameters, we establish the consistency and the oracle property of the regularized estimators. Simulation studies are conducted to illustrate the proposed methods.