Influence of human immunodeficiency virus infection on neurological impairment: an analysis of longitudinal binary data with informative drop-out

A study to investigate the human immunodeficiency virus (HIV) status on the course of neurological impairment, conducted by the HIV Center at Columbia University, followed a cohort of HIV positive and negative gay men for 5 years and assessed the presence or absence of neurological impairment every 6 months. Almost half of the subjects dropped out before the end of the study for reasons that might have been related to the missing neurological data. We propose likelihood-based methods for analysing such binary longitudinal data under informative and non-informative drop-out. A transition model is assumed for the binary response, and several models for the drop-out processes are considered which are functions of the response variable (neurological impairment). The likelihood ratio test is used to compare models with informative and non-informative drop-out mechanisms. Using simulations, we investigate the percentage bias and mean-squared error (MSE) of the parameter estimates in the transition model under various assumptions for the drop-out. We find evidence for informative drop-out in the study, and we illustrate that the bias and MSE for the parameters of the transition model are not directly related to the observed drop-out or missing data rates. The effect of HIV status on the neurological impairment is found to be statistically significant under each of the models considered for the drop-out, although the regression coefficient may be biased in certain cases. The presence and relative magnitude of the bias depend on factors such as the probability of drop-out conditional on the presence of neurological impairment and the prevalence of neurological impairment in the population under study.     

The robustness of the quasilikelihood estimator

The quasilikelihood estimator is widely used in data analysis where a likelihood is not available. We illustrate that with a given variance function it is not only conservative, in minimizing a maximum risk, but also robust against a possible misspecification of either the likelihood or cumulants of the model. In examples it is compared with estimators based on maximum likelihood and quadratic estimating functions.     

Comparison of performance measures for multivariate discrete models

For multivariate probit models, Spiess and Tutz suggest three alternative performance measures, which are all based on the decomposition of the variation. The multivariate probit model can be seen as a special case of the discrete copula model. This paper proposes some new measures based on the value of the likelihood function and the prediction-realization table. In addition, it generalizes the measures from Spiess and Tutz for the discrete copula model. Results of a simulation study designed to compare the different measures in various situations are presented.     

The Effect of Drop-Out on the Efficiency of Longitudinal Experiments

It is shown that drop-out often reduces the efficiency of longitudinal experiments considerably. In the framework of linear mixed models, a general, computationally simple method is provided, for designing longitudinal studies when drop-out is to be expected, such that there is little risk of large losses of efficiency due to the missing data. All the results are extensively illustrated using data from a randomized experiment with rats.     

Identifiable finite mixtures of location models for clustering mixed-mode data

For clustering mixed categorical and continuous data, Lawrence and Krzanowski (1996) proposed a finite mixture model in which component densities conform to the location model. In the graphical models literature the location model is known as the homogeneous Conditional Gaussian model. In this paper it is shown that their model is not identifiable without imposing additional restrictions. Specifically, for g groups and m locations, (g!)m–1 distinct sets of parameter values (not including permutations of the group mixing parameters) produce the same likelihood function. Excessive shrinkage of parameter estimates in a simulation experiment reported by Lawrence and Krzanowski (1996) is shown to be an artifact of the model's non-identifiability. Identifiable finite mixture models can be obtained by imposing restrictions on the conditional means of the continuous variables. These new identified models are assessed in simulation experiments. The conditional mean structure of the continuous variables in the restricted location mixture models is similar to that in the underlying variable mixture models proposed by Everitt (1988), but the restricted location mixture models are more computationally tractable.     

Efficacy of programmes for the unemployed: discrete time modelling of duration data from a matched-comparison study

An evaluation is described of two UK Government programmes for the long-term unemployed in Great Britain, Employment Training and Employment Action, using discrete time hazard modelling of event histories. The study design employed a closely matched comparison group and carefully chosen control variables to minimize the effect of selection bias on conclusions. The effect of unobserved heterogeneity is investigated by using some standard random effect model formulations.     

Constructing optimal designs for fitting pharmacokinetic models

We consider some computational issues that arise when searching for optimal designs for pharmacokinetic (PK) studies. Special factors that distinguish these are (i) repeated observations are taken from each subject and the observations are usually described by a nonlinear mixed model (NLMM), (ii) design criteria depend on the model fitting procedure, (iii) in addition to providing efficient parameter estimates, the design must also permit model checking, (iv) in practice there are several design constraints, (v) the design criteria are computationally expensive to evaluate and often numerical integration is needed and finally (vi) local optimisation procedures may fail to converge or get trapped at local optima.We review current optimal design algorithms and explore the possibility of using global optimisation procedures. We use these latter procedures to find some optimal designs.For multi-purpose designs we suggest two surrogate design criteria for model checking and illustrate their use.     

Two ways of modelling overdispersion in non-normal data

For non-normal data assumed to have distributions, such as the Poisson distribution, which have an a priori dispersion parameter, there are two ways of modelling overdispersion: by a quasi-likelihood approach or with a random-effect model. The two approaches yield different variance functions for the response, which may be distinguishable if adequate data are available. The epilepsy data of Thall and Vail and the fabric data of Bissell are used to exemplify the ideas.     

A general class of hierarchical ordinal regression models with applications to correlated roc analysis

The authors discuss a general class of hierarchical ordinal regression models that includes both location and scale parameters, allows link functions to be selected adaptively as finite mixtures of normal cumulative distribution functions, and incorporates flexible correlation structures for the latent scale variables. Exploiting the well‐known correspondence between ordinal regression models and parametric ROC (Receiver Operating Characteristic) curves makes it possible to use a hierarchical ROC (HROC) analysis to study multilevel clustered data in diagnostic imaging studies. The authors present a Bayesian approach to model fitting using Markov chain Monte Carlo methods and discuss HROC applications to the analysis of data from two diagnostic radiology studies involving multiple interpreters.