Estimation of group means in generalized linear mixed models

In this study, we investigate the concept of the mean response for a treatment group mean as well as its estimation and prediction for generalized linear models with a subject‐wise random effect. Generalized linear models are commonly used to analyze categorical data. The model‐based mean for a treatment group usually estimates the response at the mean covariate. However, the mean response for the treatment group for studied population is at least equally important in the context of clinical trials. New methods were proposed to estimate such a mean response in generalized linear models; however, this has only been done when there are no random effects in the model. We suggest that, in a generalized linear mixed model (GLMM), there are at least two possible definitions of a treatment group mean response that can serve as estimation/prediction targets. The estimation of these treatment group means is important for healthcare professionals to be able to understand the absolute benefit vs risk. For both of these treatment group means, we propose a new set of methods that suggests how to estimate/predict both of them in a GLMMs with a univariate subject‐wise random effect. Our methods also suggest an easy way of constructing corresponding confidence and prediction intervals for both possible treatment group means. Simulations show that proposed confidence and prediction intervals provide correct empirical coverage probability under most circumstances. Proposed methods have also been applied to analyze hypoglycemia data from diabetes clinical trials.     

Estimation of group means using Bayesian generalized linear mixed models

Generalized linear mixed models (GLMM) are commonly used to model the treatment effect over time while controlling for important clinical covariates. Standard software procedures often provide estimates of the outcome based on the mean of the covariates; however, these estimates will be biased for the true group means in the GLMM. Implementing GLMM in the frequentist framework can lead to issues of convergence. A simulation study demonstrating the use of fully Bayesian GLMM for providing unbiased estimates of group means is shown. These models are very straightforward to implement and can be used for a broad variety of outcomes (eg, binary, categorical, and count data) that arise in clinical trials. We demonstrate the proposed method on a data set from a clinical trial in diabetes.     

A flexible semiparametric regression model for bimodal,asymmetric and censored data

In this paper, we propose a new semiparametric heteroscedastic regression model allowing for positive and negative skewness and bimodal shapes using the B-spline basis for nonlinear effects. The proposed distribution is based on the generalized additive models for location, scale and shape framework in order to model any or all parameters of the distribution using parametric linear and/or nonparametric smooth functions of explanatory variables. We motivate the new model by means of Monte Carlo simulations, thus ignoring the skewness and bimodality of the random errors in semiparametric regression models, which may introduce biases on the parameter estimates and/or on the estimation of the associated variability measures. An iterative estimation process and some diagnostic methods are investigated. Applications to two real data sets are presented and the method is compared to the usual regression methods.     

Mixtures of Linear Regression with Measurement Errors

Existing research on mixtures of regression models are limited to directly observed predictors. The estimation of mixtures of regression for measurement error data imposes challenges for statisticians. For linear regression models with measurement error data, the naive ordinary least squares method, which directly substitutes the observed surrogates for the unobserved error-prone variables, yields an inconsistent estimate for the regression coefficients. The same inconsistency also happens to the naive mixtures of regression estimate, which is based on the traditional maximum likelihood estimator and simply ignores the measurement error. To solve this inconsistency, we propose to use the deconvolution method to estimate the mixture likelihood of the observed surrogates. Then our proposed estimate is found by maximizing the estimated mixture likelihood. In addition, a generalized EM algorithm is also developed to find the estimate. The simulation results demonstrate that the proposed estimation procedures work well and perform much better than the naive estimates.     

Robust methods for generalized linear models with nonignorable missing covariates

The EM algorithm is often used for finding the maximum likelihood estimates in generalized linear models with incomplete data. In this article, the author presents a robust method in the framework of the maximum likelihood estimation for fitting generalized linear models when nonignorable covariates are missing. His robust approach is useful for downweighting any influential observations when estimating the model parameters. To avoid computational problems involving irreducibly high‐dimensional integrals, he adopts a Metropolis‐Hastings algorithm based on a Markov chain sampling method. He carries out simulations to investigate the behaviour of the robust estimates in the presence of outliers and missing covariates; furthermore, he compares these estimates to the classical maximum likelihood estimates. Finally, he illustrates his approach using data on the occurrence of delirium in patients operated on for abdominal aortic aneurysm.     

Efficient Robust Estimation for Linear Models with Missing Response at Random

Coefficient estimation in linear regression models with missing data is routinely carried out in the mean regression framework. However, the mean regression theory breaks down if the error variance is infinite. In addition, correct specification of the likelihood function for existing imputation approach is often challenging in practice, especially for skewed data. In this paper, we develop a novel composite quantile regression and a weighted quantile average estimation procedure for parameter estimation in linear regression models when some responses are missing at random. Instead of imputing the missing response by randomly drawing from its conditional distribution, we propose to impute both missing and observed responses by their estimated conditional quantiles given the observed data and to use the parametrically estimated propensity scores to weigh check functions that define a regression parameter. Both estimation procedures are resistant to heavy‐tailed errors or outliers in the response and can achieve nice robustness and efficiency. Moreover, we propose adaptive penalization methods to simultaneously select significant variables and estimate unknown parameters. Asymptotic properties of the proposed estimators are carefully investigated. An efficient algorithm is developed for fast implementation of the proposed methodologies. We also discuss a model selection criterion, which is based on an IC_Q ‐type statistic, to select the penalty parameters. The performance of the proposed methods is illustrated via simulated and real data sets.     

A Simple Approach to Inference in Random Coefficient Models

Random coefficient regression models have been used to analyze cross-sectional and longitudinal data in economics and growth-curve data from biological and agricultural experiments. In the literature several estimators, including the ordinary least squares and the estimated generalized least squares (EGLS), have been considered for estimating the parameters of the mean model. Based on the asymptotic properties of the EGLS estimators, test statistics have been proposed for testing linear hypotheses involving the parameters of the mean model. An alternative estimator, the simple mean of the individual regression coefficients, provides estimation and hypothesis-testing procedures that are simple to compute and teach. The large sample properties of this simple estimator are shown to be similar to that of the EGLS estimator. The performance of the proposed estimator is compared with that of the existing estimators by Monte Carlo simulation.     

On Measuring Uncertainty of Benchmarked Predictors with Application to Disease Risk Estimate

Empirical Bayes (EB) estimates in general linear mixed models are useful for the small area estimation in the sense of increasing precision of estimation of small area means. However, one potential difficulty of EB is that the overall estimate for a larger geographical area based on a (weighted) sum of EB estimates is not necessarily identical to the corresponding direct estimate such as the overall sample mean. Another difficulty is that EB estimates yield over‐shrinking, which results in the sampling variance smaller than the posterior variance. One way to fix these problems is the benchmarking approach based on the constrained empirical Bayes (CEB) estimators, which satisfy the constraints that the aggregated mean and variance are identical to the requested values of mean and variance. In this paper, we treat the general mixed models, derive asymptotic approximations of the mean squared error (MSE) of CEB and provide second‐order unbiased estimators of MSE based on the parametric bootstrap method. These results are applied to natural exponential families with quadratic variance functions. As a specific example, the Poisson‐gamma model is dealt with, and it is illustrated that the CEB estimates and their MSE estimates work well through real mortality data.     

Generalized Weibull Linear Models

For the first time, a new class of generalized Weibull linear models is introduced to be competitive to the well-known generalized (gamma and inverse Gaussian) linear models which are adequate for the analysis of positive continuous data. The proposed models have a constant coefficient of variation for all observations similar to the gamma models and may be suitable for a wide range of practical applications in various fields such as biology, medicine, engineering, and economics, among others. We derive a joint iterative algorithm for estimating the mean and dispersion parameters. We obtain closed form expressions in matrix notation for the second-order biases of the maximum likelihood estimates of the model parameters and define bias corrected estimates. The corrected estimates are easily obtained as vectors of regression coefficients in suitable weighted linear regressions. The practical use of the new class of models is illustrated in one application to a lung cancer data set.     

Semi‐parametric small‐area estimation by combining time‐series and cross‐sectional data methods

In survey sampling, policymaking regarding the allocation of resources to subgroups (called small areas) or the determination of subgroups with specific properties in a population should be based on reliable estimates. Information, however, is often collected at a different scale than that of these subgroups; hence, the estimation can only be obtained on finer scale data. Parametric mixed models are commonly used in small‐area estimation. The relationship between predictors and response, however, may not be linear in some real situations. Recently, small‐area estimation using a generalised linear mixed model (GLMM) with a penalised spline (P‐spline) regression model, for the fixed part of the model, has been proposed to analyse cross‐sectional responses, both normal and non‐normal. However, there are many situations in which the responses in small areas are serially dependent over time. Such a situation is exemplified by a data set on the annual number of visits to physicians by patients seeking treatment for asthma, in different areas of Manitoba, Canada. In cases where covariates that can possibly predict physician visits by asthma patients (e.g. age and genetic and environmental factors) may not have a linear relationship with the response, new models for analysing such data sets are required. In the current work, using both time‐series and cross‐sectional data methods, we propose P‐spline regression models for small‐area estimation under GLMMs. Our proposed model covers both normal and non‐normal responses. In particular, the empirical best predictors of small‐area parameters and their corresponding prediction intervals are studied with the maximum likelihood estimation approach being used to estimate the model parameters. The performance of the proposed approach is evaluated using some simulations and also by analysing two real data sets (precipitation and asthma).     

Semiparametric median residual life model and inference

For randomly censored data, the authors propose a general class of semiparametric median residual life models. They incorporate covariates in a generalized linear form while leaving the baseline median residual life function completely unspecified. Despite the non‐identifiability of the survival function for a given median residual life function, a simple and natural procedure is proposed to estimate the regression parameters and the baseline median residual life function. The authors derive the asymptotic properties for the estimators, and demonstrate the numerical performance of the proposed method through simulation studies. The median residual life model can be easily generalized to model other quantiles, and the estimation method can also be applied to the mean residual life model. The Canadian Journal of Statistics 38: 665–679; 2010 © 2010 Statistical Society of Canada     

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.     

Statistical Inference and Applications of Mixture of Varying Coefficient Models

In this paper, we consider a new mixture of varying coefficient models, in which each mixture component follows a varying coefficient model and the mixing proportions and dispersion parameters are also allowed to be unknown smooth functions. We systematically study the identifiability, estimation and inference for the new mixture model. The proposed new mixture model is rather general, encompassing many mixture models as its special cases such as mixtures of linear regression models, mixtures of generalized linear models, mixtures of partially linear models and mixtures of generalized additive models, some of which are new mixture models by themselves and have not been investigated before. The new mixture of varying coefficient model is shown to be identifiable under mild conditions. We develop a local likelihood procedure and a modified expectation–maximization algorithm for the estimation of the unknown non‐parametric functions. Asymptotic normality is established for the proposed estimator. A generalized likelihood ratio test is further developed for testing whether some of the unknown functions are constants. We derive the asymptotic distribution of the proposed generalized likelihood ratio test statistics and prove that the Wilks phenomenon holds. The proposed methodology is illustrated by Monte Carlo simulations and an analysis of a CO₂‐GDP data set.     

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.     

Count Data Models with Correlated Unobserved Heterogeneity

Abstract. As previously argued, the correlation between included and omitted regressors generally causes inconsistency of standard estimators for count data models. Non‐linear instrumental variables estimation of an exponential model under conditional moment restrictions is one of the proposed remedies. This approach is extended here by fully exploiting the model assumptions and thereby improving efficiency of the resulting estimator. Empirical likelihood in particular has favourable properties in this setting compared with the two‐step generalized method of moments, as demonstrated in a Monte Carlo experiment. The proposed method is applied to the estimation of a cigarette demand function.     

A pseudo‐empirical best linear unbiased prediction approach to small area estimation using survey weights

The authors develop a small area estimation method using a nested error linear regression model and survey weights. In particular, they propose a pseudo‐empirical best linear unbiased prediction (pseudo‐EBLUP) estimator to estimate small area means. This estimator borrows strength across areas through the model and makes use of the survey weights to preserve the design consistency as the area sample size increases. The proposed estimator also has a nice self‐benchmarking property. The authors also obtain an approximation to the model mean squared error (MSE) of the proposed estimator and a nearly unbiased estimator of MSE. Finally, they compare the proposed estimator with the EBLUP estimator and the pseudo‐EBLUP estimator proposed by Prasad & Rao (1999), using data analyzed earlier by Battese, Harter & Fuller (1988).     

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.     

Using continuation-ratio logits to analyze the variation of the age composition of fish catches

Major sources of information for the estimation of the size of the fish stocks and the rate of their exploitation are samples from which the age composition of catches may be determined. However, the age composition in the catches often varies as a result of several factors. Stratification of the sampling is desirable, because it leads to better estimates of the age composition, and the corresponding variances and covariances. The analysis is impeded by the fact that the response is ordered categorical. This paper introduces an easily applicable method to analyze such data. The method combines continuation-ratio logits and the theory for generalized linear mixed models. Continuation-ratio logits are designed for ordered multinomial response and have the feature that the associated log-likelihood splits into separate terms for each category levels. Thus, generalized linear mixed models can be applied separately to each level of the logits. The method is illustrated by the analysis of age-composition data collected from the Danish sandeel fishery in the North Sea in 1993. The significance of possible sources of variation is evaluated, and formulae for estimating the proportions of each age group and their variance-covariance matrix are derived.     

Small Area Estimation Using Estimated Population Level Auxiliary Data

Unit level linear mixed models are often used in small area estimation (SAE), and the empirical best linear unbiased prediction (EBLUP) is widely used for the estimation of small area means under such models. However, EBLUP requires population level auxiliary data, atleast area specific aggregated values. Sometimes population level auxiliary data is either not available or not consistent with the survey data. We describe a SAE method that uses estimated population auxiliary information. Empirical results show that proposed method for SAE produces an efficient set of small area estimates.     

A semi-parametric approach to robust parameter design

Parameter design or robust parameter design (RPD) is an engineering methodology intended as a cost-effective approach for improving the quality of products and processes. The goal of parameter design is to choose the levels of the control variables that optimize a defined quality characteristic. An essential component of RPD involves the assumption of well estimated models for the process mean and variance. Traditionally, the modeling of the mean and variance has been done parametrically. It is often the case, particularly when modeling the variance, that nonparametric techniques are more appropriate due to the nature of the curvature in the underlying function. Most response surface experiments involve sparse data. In sparse data situations with unusual curvature in the underlying function, nonparametric techniques often result in estimates with problematic variation whereas their parametric counterparts may result in estimates with problematic bias. We propose the use of semi-parametric modeling within the robust design setting, combining parametric and nonparametric functions to improve the quality of both mean and variance model estimation. The proposed method will be illustrated with an example and simulations.