Dynamic latent trait models with mixed hidden Markov structure for mixed longitudinal outcomes

We propose a general Bayesian joint modeling approach to model mixed longitudinal outcomes from the exponential family for taking into account any differential misclassification that may exist among categorical outcomes. Under this framework, outcomes observed without measurement error are related to latent trait variables through generalized linear mixed effect models. The misclassified outcomes are related to the latent class variables, which represent unobserved real states, using mixed hidden Markov models (MHMMs). In addition to enabling the estimation of parameters in prevalence, transition and misclassification probabilities, MHMMs capture cluster level heterogeneity. A transition modeling structure allows the latent trait and latent class variables to depend on observed predictors at the same time period and also on latent trait and latent class variables at previous time periods for each individual. Simulation studies are conducted to make comparisons with traditional models in order to illustrate the gains from the proposed approach. The new approach is applied to data from the Southern California Children Health Study to jointly model questionnaire-based asthma state and multiple lung function measurements in order to gain better insight about the underlying biological mechanism that governs the inter-relationship between asthma state and lung function development.     

General location multivariate latent variable models for mixed correlated bounded continuous,ordinal, and nominal responses with non-ignorable missing data

Using a multivariate latent variable approach, this article proposes some new general models to analyze the correlated bounded continuous and categorical (nominal or/and ordinal) responses with and without non-ignorable missing values. First, we discuss regression methods for jointly analyzing continuous, nominal, and ordinal responses that we motivated by analyzing data from studies of toxicity development. Second, using the beta and Dirichlet distributions, we extend the models so that some bounded continuous responses are replaced for continuous responses. The joint distribution of the bounded continuous, nominal and ordinal variables is decomposed into a marginal multinomial distribution for the nominal variable and a conditional multivariate joint distribution for the bounded continuous and ordinal variables given the nominal variable. We estimate the regression parameters under the new general location models using the maximum-likelihood method. Sensitivity analysis is also performed to study the influence of small perturbations of the parameters of the missing mechanisms of the model on the maximal normal curvature. The proposed models are applied to two data sets: BMI, Steatosis and Osteoporosis data and Tehran household expenditure budgets.     

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.     

Mixture separation for mixed-mode data

One possible approach to cluster analysis is the mixture maximum likelihood method, in which the data to be clustered are assumed to come from a finite mixture of populations. The method has been well developed, and much used, for the case of multivariate normal populations. Practical applications, however, often involve mixtures of categorical and continuous variables. Everitt (1988) and Everitt and Merette (1990) recently extended the normal model to deal with such data by incorporating the use of thresholds for the categorical variables. The computations involved in this model are so extensive, however, that it is only feasible for data containing very few categorical variables. In the present paper we consider an alternative model, known as the homogeneous Conditional Gaussian model in graphical modelling and as the location model in discriminant analysis. We extend this model to the finite mixture situation, obtain maximum likelihood estimates for the population parameters, and show that computation is feasible for an arbitrary number of variables. Some data sets are clustered by this method, and a small simulation study demonstrates characteristics of its performance.     

A comparison of methods for simulating correlated binary variables with specified marginal means and correlations

Simulation studies employed to study properties of estimators for parameters in population-average models for clustered or longitudinal data require suitable algorithms for data generation. Methods for generating correlated binary data that allow general specifications of the marginal mean and correlation structures are particularly useful. We compare an algorithm based on dichotomizing multi-normal variates to one based on a conditional linear family (CLF) of distributions [Qaqish BF. A family of multivariate binary distributions for simulating correlated binary variables with specified marginal means and correlations. Biometrika. 2003;90:455–463] with respect to range restrictions induced on correlations. Examples include generating longitudinal binary data and generating correlated binary data compatible with specified marginal means and covariance structures for bivariate, overdispersed binomial outcomes. Results show the CLF method gives a wider range of correlations for longitudinal data having autocorrelated within-subject associations, while the multivariate probit method gives a wider range of correlations for clustered data having exchangeable-type correlations. In the case of a decaying-product correlation structure, it is shown that the CLF method achieves the nonparametric limits on the range of correlations, which cannot be surpassed by any method.     

Gaussian copula distributions for mixed data,with application in discrimination

The construction of a joint model for mixed discrete and continuous random variables that accounts for their associations is an important statistical problem in many practical applications. In this paper, we use copulas to construct a class of joint distributions of mixed discrete and continuous random variables. In particular, we employ the Gaussian copula to generate joint distributions for mixed variables. Examples include the robit-normal and probit-normal-exponential distributions, the first for modelling the distribution of mixed binary-continuous data and the second for a mixture of continuous, binary and trichotomous variables. The new class of joint distributions is general enough to include many mixed-data models currently available. We study properties of the distributions and outline likelihood estimation; a small simulation study is used to investigate the finite-sample properties of estimates obtained by full and pairwise likelihood methods. Finally, we present an application to discriminant analysis of multiple correlated binary and continuous data from a study involving advanced breast cancer patients.     

Joint regression modeling for missing categorical covariates in generalized linear models

Missing covariates data is a common issue in generalized linear models (GLMs). A model-based procedure arising from properly specifying joint models for both the partially observed covariates and the corresponding missing indicator variables represents a sound and flexible methodology, which lends itself to maximum likelihood estimation as the likelihood function is available in computable form. In this paper, a novel model-based methodology is proposed for the regression analysis of GLMs when the partially observed covariates are categorical. Pair-copula constructions are used as graphical tools in order to facilitate the specification of the high-dimensional probability distributions of the underlying missingness components. The model parameters are estimated by maximizing the weighted log-likelihood function by using an EM algorithm. In order to compare the performance of the proposed methodology with other well-established approaches, which include complete-cases and multiple imputation, several simulation experiments of Binomial, Poisson and Normal regressions are carried out under both missing at random and non-missing at random mechanisms scenarios. The methods are illustrated by modeling data from a stage III melanoma clinical trial. The results show that the methodology is rather robust and flexible, representing a competitive alternative to traditional techniques.     

On Two General Classes of Discrete Bivariate Distributions

In this article, we develop two general classes of discrete bivariate distributions. We derive general formulas for the joint distributions belonging to the classes. The obtained formulas for the joint distributions are very general in the sense that new families of distributions can be generated just by specifying the “baseline seed distributions.” The dependence structures of the bivariate distributions belonging to the proposed classes, along with basic statistical properties, are also discussed. New families of discrete bivariate distributions are generated from the classes. Furthermore, to assess the usefulness of the proposed classes, two discrete bivariate distributions generated from the classes are applied to analyze a real dataset and the results are compared with those obtained from conventional models.     

Bayesian Methods for Missing Covariates in Cure Rate Models

We propose methods for Bayesian inference for missing covariate data with a novel class of semi-parametric survival models with a cure fraction. We allow the missing covariates to be either categorical or continuous and specify a parametric distribution for the covariates that is written as a sequence of one dimensional conditional distributions. We assume that the missing covariates are missing at random (MAR) throughout. We propose an informative class of joint prior distributions for the regression coefficients and the parameters arising from the covariate distributions. The proposed class of priors are shown to be useful in recovering information on the missing covariates especially in situations where the missing data fraction is large. Properties of the proposed prior and resulting posterior distributions are examined. Also, model checking techniques are proposed for sensitivity analyses and for checking the goodness of fit of a particular model. Specifically, we extend the Conditional Predictive Ordinate (CPO) statistic to assess goodness of fit in the presence of missing covariate data. Computational techniques using the Gibbs sampler are implemented. A real data set involving a melanoma cancer clinical trial is examined to demonstrate the methodology.     

Bayesian Kernel Mixtures for Counts

Although Bayesian nonparametric mixture models for continuous data are well developed, there is a limited literature on related approaches for count data. A common strategy is to use a mixture of Poissons, which unfortunately is quite restrictive in not accounting for distributions having variance less than the mean. Other approaches include mixing multinomials, which requires finite support, and using a Dirichlet process prior with a Poisson base measure, which does not allow smooth deviations from the Poisson. As a broad class of alternative models, we propose to use nonparametric mixtures of rounded continuous kernels. An efficient Gibbs sampler is developed for posterior computation, and a simulation study is performed to assess performance. Focusing on the rounded Gaussian case, we generalize the modeling framework to account for multivariate count data, joint modeling with continuous and categorical variables, and other complications. The methods are illustrated through applications to a developmental toxicity study and marketing data. This article has supplementary material online.     

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 generalized bivariate Bernoulli model with covariate dependence

Dependence in outcome variables may pose formidable difficulty in analyzing data in longitudinal studies. In the past, most of the studies made attempts to address this problem using the marginal models. However, using the marginal models alone, it is difficult to specify the measures of dependence in outcomes due to association between outcomes as well as between outcomes and explanatory variables. In this paper, a generalized approach is demonstrated using both the conditional and marginal models. This model uses link functions to test for dependence in outcome variables. The estimation and test procedures are illustrated with an application to the mobility index data from the Health and Retirement Survey and also simulations are performed for correlated binary data generated from the bivariate Bernoulli distributions. The results indicate the usefulness of the proposed method.     

Bayesian inference for bivariate generalized linear models in diagnosing renal arterial obstruction

Generalized linear models are well-established generalizations of the linear models used for regression and analysis of variance. They allow flexible mean structures and general distributions, other than the linear link and normal response assumed in regression. Further enhancements using ideas from multivariate analysis improve power and precision by modelling dependencies between response variables. This paper focuses on the specific case of regression models for bivariate Bernoulli responses and investigates their analysis using a Bayesian approach. The important problem of renal arterial obstruction is considered, as a medical application of these models.     

Nonparametric likelihood and doubly robust estimating equations for marginal and nested structural models

This article considers Robins's marginal and nested structural models in the cross‐sectional setting and develops likelihood and regression estimators. First, a nonparametric likelihood method is proposed by retaining a finite subset of all inherent and modelling constraints on the joint distributions of potential outcomes and covariates under a correctly specified propensity score model. A profile likelihood is derived by maximizing the nonparametric likelihood over these joint distributions subject to the retained constraints. The maximum likelihood estimator is intrinsically efficient based on the retained constraints and weakly locally efficient. Second, two regression estimators, named hat and tilde, are derived as first‐order approximations to the likelihood estimator under the propensity score model. The tilde regression estimator is intrinsically and weakly locally efficient and doubly robust. The methods are illustrated by data analysis for an observational study on right heart catheterization. The Canadian Journal of Statistics 38: 609–632; 2010 © 2010 Statistical Society of Canada     

Sequential imputation for models with latent variables assuming latent ignorability

Models that involve an outcome variable, covariates, and latent variables are frequently the target for estimation and inference. The presence of missing covariate or outcome data presents a challenge, particularly when missingness depends on the latent variables. This missingness mechanism is called latent ignorable or latent missing at random and is a generalisation of missing at random. Several authors have previously proposed approaches for handling latent ignorable missingness, but these methods rely on prior specification of the joint distribution for the complete data. In practice, specifying the joint distribution can be difficult and/or restrictive. We develop a novel sequential imputation procedure for imputing covariate and outcome data for models with latent variables under latent ignorable missingness. The proposed method does not require a joint model; rather, we use results under a joint model to inform imputation with less restrictive modelling assumptions. We discuss identifiability and convergence‐related issues, and simulation results are presented in several modelling settings. The method is motivated and illustrated by a study of head and neck cancer recurrence. Imputing missing data for models with latent variables under latent‐dependent missingness without specifying a full joint model.     

A Bayesian analysis of clustered discrete and continuous outcomes

Many study designs yield a variety of outcomes from each subject clustered within an experimental unit. When these outcomes are of mixed data types, it is challenging to jointly model the effects of covariates on the responses using traditional methods. In this paper, we develop a Bayesian approach for a joint regression model of the different outcome variables and show that the fully conditional posterior distributions obtained under the model assumptions allow for estimation of posterior distributions using Gibbs sampling algorithm.     

Generalized additive models for location, scale and shape

Summary.  A general class of statistical models for a univariate response variable is presented which we call the generalized additive model for location, scale and shape (GAMLSS). The model assumes independent observations of the response variable y given the parameters, the explanatory variables and the values of the random effects. The distribution for the response variable in the GAMLSS can be selected from a very general family of distributions including highly skew or kurtotic continuous and discrete distributions. The systematic part of the model is expanded to allow modelling not only of the mean (or location) but also of the other parameters of the distribution of y , as parametric and/or additive nonparametric (smooth) functions of explanatory variables and/or random-effects terms. Maximum (penalized) likelihood estimation is used to fit the (non)parametric models. A Newton–Raphson or Fisher scoring algorithm is used to maximize the (penalized) likelihood. The additive terms in the model are fitted by using a backfitting algorithm. Censored data are easily incorporated into the framework. Five data sets from different fields of application are analysed to emphasize the generality of the GAMLSS class of models.     

Functional approach of flexibly modelling generalized longitudinal data and survival time

We propose a flexible functional approach for modelling generalized longitudinal data and survival time using principal components. In the proposed model the longitudinal observations can be continuous or categorical data, such as Gaussian, binomial or Poisson outcomes. We generalize the traditional joint models that treat categorical data as continuous data by using some transformations, such as CD4 counts. The proposed model is data-adaptive, which does not require pre-specified functional forms for longitudinal trajectories and automatically detects characteristic patterns. The longitudinal trajectories observed with measurement error or random error are represented by flexible basis functions through a possibly nonlinear link function, combining dimension reduction techniques resulting from functional principal component (FPC) analysis. The relationship between the longitudinal process and event history is assessed using a Cox regression model. Although the proposed model inherits the flexibility of non-parametric methods, the estimation procedure based on the EM algorithm is still parametric in computation, and thus simple and easy to implement. The computation is simplified by dimension reduction for random coefficients or FPC scores. An iterative selection procedure based on Akaike information criterion (AIC) is proposed to choose the tuning parameters, such as the knots of spline basis and the number of FPCs, so that appropriate degree of smoothness and fluctuation can be addressed. The effectiveness of the proposed approach is illustrated through a simulation study, followed by an application to longitudinal CD4 counts and survival data which were collected in a recent clinical trial to compare the efficiency and safety of two antiretroviral drugs.     

Missing covariates in generalized linear models when the missing data mechanism is non-ignorable

We propose a method for estimating parameters in generalized linear models with missing covariates and a non-ignorable missing data mechanism. We use a multinomial model for the missing data indicators and propose a joint distribution for them which can be written as a sequence of one-dimensional conditional distributions, with each one-dimensional conditional distribution consisting of a logistic regression. We allow the covariates to be either categorical or continuous. The joint covariate distribution is also modelled via a sequence of one-dimensional conditional distributions, and the response variable is assumed to be completely observed. We derive the E- and M-steps of the EM algorithm with non-ignorable missing covariate data. For categorical covariates, we derive a closed form expression for the E- and M-steps of the EM algorithm for obtaining the maximum likelihood estimates (MLEs). For continuous covariates, we use a Monte Carlo version of the EM algorithm to obtain the MLEs via the Gibbs sampler. Computational techniques for Gibbs sampling are proposed and implemented. The parametric form of the assumed missing data mechanism itself is not `testable' from the data, and thus the non-ignorable modelling considered here can be viewed as a sensitivity analysis concerning a more complicated model. Therefore, although a model may have `passed' the tests for a certain missing data mechanism, this does not mean that we have captured, even approximately, the correct missing data mechanism. Hence, model checking for the missing data mechanism and sensitivity analyses play an important role in this problem and are discussed in detail. Several simulations are given to demonstrate the methodology. In addition, a real data set from a melanoma cancer clinical trial is presented to illustrate the methods proposed.     

Building and Fitting Non‐Gaussian Latent Variable Models via the Moment‐Generating Function

Abstract. For certain classes of hierarchical models, it is easy to derive an expression for the joint moment‐generating function (MGF) of data, whereas the joint probability density has an intractable form which typically involves an integral. The most important example is the class of linear models with non‐Gaussian latent variables. Parameters in the model can be estimated by approximate maximum likelihood, using a saddlepoint‐type approximation to invert the MGF. We focus on modelling heavy‐tailed latent variables, and suggest a family of mixture distributions that behaves well under the saddlepoint approximation (SPA). It is shown that the well‐known normalization issue renders the ordinary SPA useless in the present context. As a solution we extend the non‐Gaussian leading term SPA to a multivariate setting, and introduce a general rule for choosing the leading term density. The approach is applied to mixed‐effects regression, time‐series models and stochastic networks and it is shown that the modified SPA is very accurate.