Estimation and prediction for spatial generalized linear mixed models using high order Laplace approximation

Estimation and prediction in generalized linear mixed models are often hampered by intractable high dimensional integrals. This paper provides a framework to solve this intractability, using asymptotic expansions when the number of random effects is large. To that end, we first derive a modified Laplace approximation when the number of random effects is increasing at a lower rate than the sample size. Second, we propose an approximate likelihood method based on the asymptotic expansion of the log-likelihood using the modified Laplace approximation which is maximized using a quasi-Newton algorithm. Finally, we define the second order plug-in predictive density based on a similar expansion to the plug-in predictive density and show that it is a normal density. Our simulations show that in comparison to other approximations, our method has better performance. Our methods are readily applied to non-Gaussian spatial data and as an example, the analysis of the rhizoctonia root rot data is presented.     

Longitudinal Data Estimating Equations for Dispersion Models

Liang & Zeger's generalized estimating equation approach for analysis of longitudinal data is extended to marginal distributions of dispersion model type. This includes for example the von Mises and simplex distributions, suitable for angles and proportions, respectively. Both modelling of position and joint modelling of position and dispersion is considered, and the method is applied to a set of bird orientation data.     

Estimation and inference of the joint conditional distribution for multivariate longitudinal data using nonparametric copulas

In this paper we study estimating the joint conditional distributions of multivariate longitudinal outcomes using regression models and copulas. For the estimation of marginal models, we consider a class of time-varying transformation models and combine the two marginal models using nonparametric empirical copulas. Our models and estimation method can be applied in many situations where the conditional mean-based models are not good enough. Empirical copulas combined with time-varying transformation models may allow quite flexible modelling for the joint conditional distributions for multivariate longitudinal data. We derive the asymptotic properties for the copula-based estimators of the joint conditional distribution functions. For illustration we apply our estimation method to an epidemiological study of childhood growth and blood pressure.     

Joint Modelling of Survival and Longitudinal Data with Informative Observation Times

In this paper, we consider the joint modelling of survival and longitudinal data with informative observation time points. The survival model and the longitudinal model are linked via random effects, for which no distribution assumption is required under our estimation approach. The estimator is shown to be consistent and asymptotically normal. The proposed estimator and its estimated covariance matrix can be easily calculated. Simulation studies and an application to a primary biliary cirrhosis study are also provided.     

ASYMPTOTIC LIKELIHOOD APPROXIMATIONS USING A PARTIAL LAPLACE APPROXIMATION

Elimination of a nuisance variable is often non‐trivial and may involve the evaluation of an intractable integral. One approach to evaluate these integrals is to use the Laplace approximation. This paper concentrates on a new approximation, called the partial Laplace approximation, that is useful when the integrand can be partitioned into two multiplicative disjoint functions. The technique is applied to the linear mixed model and shows that the approximate likelihood obtained can be partitioned to provide a conditional likelihood for the location parameters and a marginal likelihood for the scale parameters equivalent to restricted maximum likelihood (REML). Similarly, the partial Laplace approximation is applied to the t‐distribution to obtain an approximate REML for the scale parameter. A simulation study reveals that, in comparison to maximum likelihood, the scale parameter estimates of the t‐distribution obtained from the approximate REML show reduced bias.     

Sampling Adjusted Analysis of Dynamic Additive Regression Models for Longitudinal Data

We consider a modelling approach to longitudinal data that aims at estimating flexible covariate effects in a model where the sampling probabilities are modelled explicitly. The joint modelling yields simple estimators that are easy to compute and analyse, even if the sampling of the longitudinal responses interacts with the response level. An incorrect model for the sampling probabilities results in biased estimates. Non-representative sampling occurs, for example, if patients with an extreme development (based on extreme values of the response) are called in for additional examinations and measurements. We allow covariate effects to be time-varying or time-constant. Estimates of covariate effects are obtained by solving martingale equations locally for the cumulative regression functions. Using Aalen's additive model for the sampling probabilities, we obtain simple expressions for the estimators and their asymptotic variances. The asymptotic distributions for the estimators of the non-parametric components as well as the parametric components of the model are derived drawing on general martingale results. Two applications are presented. We consider the growth of cystic fibrosis patients and the prothrombin index for liver cirrhosis patients. The conclusion about the growth of the cystic fibrosis patients is not altered when adjusting for a possible non-representativeness in the sampling, whereas we reach substantively different conclusions about the treatment effect for the liver cirrhosis patients.     

Jointly modeling longitudinal proportional data and survival times with an application to the quality of life data in a breast cancer trial

Motivated by the joint analysis of longitudinal quality of life data and recurrence free survival times from a cancer clinical trial, we present in this paper two approaches to jointly model the longitudinal proportional measurements, which are confined in a finite interval, and survival data. Both approaches assume a proportional hazards model for the survival times. For the longitudinal component, the first approach applies the classical linear mixed model to logit transformed responses, while the second approach directly models the responses using a simplex distribution. A semiparametric method based on a penalized joint likelihood generated by the Laplace approximation is derived to fit the joint model defined by the second approach. The proposed procedures are evaluated in a simulation study and applied to the analysis of breast cancer data motivated this research.     

Comparing crossing hazard rate functions by joint modelling of survival and longitudinal data

Abstract

It is one of the important issues in survival analysis to compare two hazard rate functions to evaluate treatment effect. It is quite common that the two hazard rate functions cross each other at one or more unknown time points, representing temporal changes of the treatment effect. In certain applications, besides survival data, we also have related longitudinal data available regarding some time-dependent covariates. In such cases, a joint model that accommodates both types of data can allow us to infer the association between the survival and longitudinal data and to assess the treatment effect better. In this paper, we propose a modelling approach for comparing two crossing hazard rate functions by joint modelling survival and longitudinal data. Maximum likelihood estimation is used in estimating the parameters of the proposed joint model using the EM algorithm. Asymptotic properties of the maximum likelihood estimators are studied. To illustrate the virtues of the proposed method, we compare the performance of the proposed method with several existing methods in a simulation study. Our proposed method is also demonstrated using a real dataset obtained from an HIV clinical trial.     

Bayesian quantile regression for hierarchical linear models

The paper proposes a Bayesian quantile regression method for hierarchical linear models. Existing approaches of hierarchical linear quantile regression models are scarce and most of them were not from the perspective of Bayesian thoughts, which is important for hierarchical models. In this paper, based on Bayesian theories and Markov Chain Monte Carlo methods, we introduce Asymmetric Laplace distributed errors to simulate joint posterior distributions of population parameters and across-unit parameters and then derive their posterior quantile inferences. We run a simulation as the proposed method to examine the effects on parameters induced by units and quantile levels; the method is also applied to study the relationship between Chinese rural residents' family annual income and their cultivated areas. Both the simulation and real data analysis indicate that the method is effective and accurate.     

Time-varying coefficient models with ARMA–GARCH structures for longitudinal data analysis

Time-varying coefficient models with autoregressive and moving-average–generalized autoregressive conditional heteroscedasticity structure are proposed for examining the time-varying effects of risk factors in longitudinal studies. Compared with existing models in the literature, the proposed models give explicit patterns for the time-varying coefficients. Maximum likelihood and marginal likelihood (based on a Laplace approximation) are used to estimate the parameters in the proposed models. Simulation studies are conducted to evaluate the performance of these two estimation methods, which is measured in terms of the Kullback–Leibler divergence and the root mean square error. The marginal likelihood approach leads to the more accurate parameter estimates, although it is more computationally intensive. The proposed models are applied to the Framingham Heart Study to investigate the time-varying effects of covariates on coronary heart disease incidence. The Bayesian information criterion is used for specifying the time series structures of the coefficients of the risk factors.     

Disaggregated spatial modelling for areal unit categorical data

Summary.  We consider joint spatial modelling of areal multivariate categorical data assuming a multiway contingency table for the variables, modelled by using a log-linear model, and connected across units by using spatial random effects. With no distinction regarding whether variables are response or explanatory, we do not limit inference to conditional probabilities, as in customary spatial logistic regression. With joint probabilities we can calculate arbitrary marginal and conditional probabilities without having to refit models to investigate different hypotheses. Flexible aggregation allows us to investigate subgroups of interest; flexible conditioning enables not only the study of outcomes given risk factors but also retrospective study of risk factors given outcomes. A benefit of joint spatial modelling is the opportunity to reveal disparities in health in a richer fashion, e.g. across space for any particular group of cells, across groups of cells at a particular location, and, hence, potential space–group interaction. We illustrate with an analysis of birth records for the state of North Carolina and compare with spatial logistic regression.     

A joint model for hierarchical continuous and zero-inflated overdispersed count data

Many applications in public health, medical and biomedical or other studies demand modelling of two or more longitudinal outcomes jointly to get better insight into their joint evolution. In this regard, a joint model for a longitudinal continuous and a count sequence, the latter possibly overdispersed and zero-inflated (ZI), will be specified that assembles aspects coming from each one of them into one single model. Further, a subject-specific random effect is included to account for the correlation in the continuous outcome. For the count outcome, clustering and overdispersion are accommodated through two distinct sets of random effects in a generalized linear model as proposed by Molenberghs et al. [A family of generalized linear models for repeated measures with normal and conjugate random effects. Stat Sci. 2010;25:325–347]; one is normally distributed, the other conjugate to the outcome distribution. The association among the two sequences is captured by correlating the normal random effects describing the continuous and count outcome sequences, respectively. An excessive number of zero counts is often accounted for by using a so-called ZI or hurdle model. ZI models combine either a Poisson or negative-binomial model with an atom at zero as a mixture, while the hurdle model separately handles the zero observations and the positive counts. This paper proposes a general joint modelling framework in which all these features can appear together. We illustrate the proposed method with a case study and examine it further with simulations.     

A modified two-stage approach for joint modelling of longitudinal and time-to-event data

Joint models for longitudinal and time-to-event data have been applied in many different fields of statistics and clinical studies. However, the main difficulty these models have to face with is the computational problem. The requirement for numerical integration becomes severe when the dimension of random effects increases. In this paper, a modified two-stage approach has been proposed to estimate the parameters in joint models. In particular, in the first stage, the linear mixed-effects models and best linear unbiased predictorsare applied to estimate parameters in the longitudinal submodel. In the second stage, an approximation of the fully joint log-likelihood is proposed using the estimated the values of these parameters from the longitudinal submodel. Survival parameters are estimated bymaximizing the approximation of the fully joint log-likelihood. Simulation studies show that the approach performs well, especially when the dimension of random effects increases. Finally, we implement this approach on AIDS data.     

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.     

Selection Strategy for Covariance Structure of Random Effects in Linear Mixed‐effects Models

Linear mixed‐effects models are a powerful tool for modelling longitudinal data and are widely used in practice. For a given set of covariates in a linear mixed‐effects model, selecting the covariance structure of random effects is an important problem. In this paper, we develop a joint likelihood‐based selection criterion. Our criterion is the approximately unbiased estimator of the expected Kullback–Leibler information. This criterion is also asymptotically optimal in the sense that for large samples, estimates based on the covariance matrix selected by the criterion minimize the approximate Kullback–Leibler information. Finite sample performance of the proposed method is assessed by simulation experiments. As an illustration, the criterion is applied to a data set from an AIDS clinical trial.     

Joint models for multiple longitudinal processes and time-to-event outcome

ABSTRACT

Joint models are statistical tools for estimating the association between time-to-event and longitudinal outcomes. One challenge to the application of joint models is its computational complexity. Common estimation methods for joint models include a two-stage method, Bayesian and maximum-likelihood methods. In this work, we consider joint models of a time-to-event outcome and multiple longitudinal processes and develop a maximum-likelihood estimation method using the expectation–maximization algorithm. We assess the performance of the proposed method via simulations and apply the methodology to a data set to determine the association between longitudinal systolic and diastolic blood pressure measures and time to coronary artery disease.     

Bayesian inference for generalized additive mixed models based on Markov random field priors

Most regression problems in practice require flexible semiparametric forms of the predictor for modelling the dependence of responses on covariates. Moreover, it is often necessary to add random effects accounting for overdispersion caused by unobserved heterogeneity or for correlation in longitudinal or spatial data. We present a unified approach for Bayesian inference via Markov chain Monte Carlo simulation in generalized additive and semiparametric mixed models. Different types of covariates, such as the usual covariates with fixed effects, metrical covariates with non-linear effects, unstructured random effects, trend and seasonal components in longitudinal data and spatial covariates, are all treated within the same general framework by assigning appropriate Markov random field priors with different forms and degrees of smoothness. We applied the approach in several case-studies and consulting cases, showing that the methods are also computationally feasible in problems with many covariates and large data sets. In this paper, we choose two typical applications.     

The Analysis of Designed Experiments and Longitudinal Data by Using Smoothing Splines

In designed experiments and in particular longitudinal studies, the aim may be to assess the effect of a quantitative variable such as time on treatment effects. Modelling treatment effects can be complex in the presence of other sources of variation. Three examples are presented to illustrate an approach to analysis in such cases. The first example is a longitudinal experiment on the growth of cows under a factorial treatment structure where serial correlation and variance heterogeneity complicate the analysis. The second example involves the calibration of optical density and the concentration of a protein DNase in the presence of sampling variation and variance heterogeneity. The final example is a multienvironment agricultural field experiment in which a yield–seeding rate relationship is required for several varieties of lupins. Spatial variation within environments, heterogeneity between environments and variation between varieties all need to be incorporated in the analysis. In this paper, the cubic smoothing spline is used in conjunction with fixed and random effects, random coefficients and variance modelling to provide simultaneous modelling of trends and covariance structure. The key result that allows coherent and flexible empirical model building in complex situations is the linear mixed model representation of the cubic smoothing spline. An extension is proposed in which trend is partitioned into smooth and non-smooth components. Estimation and inference, the analysis of the three examples and a discussion of extensions and unresolved issues are also presented.     

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.     

Statistical analysis of performance indicators in UK higher education

Summary.  Attempts to measure the quality with which institutions such as hospitals and universities carry out their public mandates have gained in frequency and sophistication over the last decade. We examine methods for creating performance indicators in multilevel or hierarchical settings (e.g. students nested within universities) based on a dichotomous outcome variable (e.g. drop-out from the higher education system). The profiling methods that we study involve the indirect measurement of quality, by comparing institutional outputs after adjusting for inputs, rather than directly attempting to measure the quality of the processes unfolding inside the institutions. In the context of an extended case-study of the creation of performance indicators for universities in the UK higher education system, we demonstrate the large sample functional equivalence between a method based on indirect standardization and an approach based on fixed effects hierarchical modelling, offer simulation results on the performance of the standardization method in null and non-null settings, examine the sensitivity of this method to the inadvertent omission of relevant adjustment variables, explore random-effects reformulations and characterize settings in which they are preferable to fixed effects hierarchical modelling in this type of quality assessment and discuss extensions to longitudinal quality modelling and the overall pros and cons of institutional profiling. Our results are couched in the language of higher education but apply with equal force to other settings with dichotomous response variables, such as the examination of observed and expected rates of mortality (or other adverse outcomes) in investigations of the quality of health care or the study of retention rates in the workplace.