Latent transition models with latent class predictors: attention deficit hyperactivity disorder subtypes and high school marijuana use

Summary.  Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder which is most often diagnosed in childhood with symptoms often persisting into adulthood. Elevated rates of substance use disorders have been evidenced among those with ADHD, but recent research focusing on the relationship between subtypes of ADHD and specific drugs is inconsistent. We propose a latent transition model (LTM) to guide our understanding of how drug use progresses, in particular marijuana use, while accounting for the measurement error that is often found in self-reported substance use data. We extend the LTM to include a latent class predictor to represent empirically derived ADHD subtypes that do not rely on meeting specific diagnostic criteria. We begin by fitting two separate latent class analysis (LCA) models by using second-order estimating equations: a longitudinal LCA model to define stages of marijuana use, and a cross-sectional LCA model to define ADHD subtypes. The LTM model parameters describing the probability of transitioning between the LCA-defined stages of marijuana use and the influence of the LCA-defined ADHD subtypes on these transition rates are then estimated by using a set of first-order estimating equations given the LCA parameter estimates. A robust estimate of the LTM parameter variance that accounts for the variation due to the estimation of the two sets of LCA parameters is proposed. Solving three sets of estimating equations enables us to determine the underlying latent class structures independently of the model for the transition rates and simplifying assumptions about the correlation structure at each stage reduces the computational complexity.     

Identification of Multivariate Responders/Non-Responders Using Bayesian Growth Curve Latent Class Models

In this paper, we propose a multivariate growth curve mixture model that groups subjects based on multiple symptoms measured repeatedly over time. Our model synthesizes features of two models. First, we follow Roy and Lin (2000) in relating the multiple symptoms at each time point to a single latent variable. Second, we use the growth mixture model of Muthén and Shedden (1999) to group subjects based on distinctive longitudinal profiles of this latent variable. The mean growth curve for the latent variable in each class defines that class's features. For example, a class of "responders" would have a decline in the latent symptom summary variable over time. A Bayesian approach to estimation is employed where the methods of Elliott et al (2005) are extended to simultaneously estimate the posterior distributions of the parameters from the latent variable and growth curve mixture portions of the model. We apply our model to data from a randomized clinical trial evaluating the efficacy of Bacillus Calmette-Guerin (BCG) in treating symptoms of Interstitial Cystitis. In contrast to conventional approaches using a single subjective Global Response Assessment, we use the multivariate symptom data to identify a class of subjects where treatment demonstrates effectiveness. Simulations are used to confirm identifiability results and evaluate the performance of our algorithm. The definitive version of this paper is available at onlinelibrary.wiley.com.     

Modeling Longitudinal Obesity Data with Intermittent Missingness Using a New Latent Variable Model

We propose a latent variable model for informative missingness in longitudinal studies which is an extension of latent dropout class model. In our model, the value of the latent variable is affected by the missingness pattern and it is also used as a covariate in modeling the longitudinal response. So the latent variable links the longitudinal response and the missingness process. In our model, the latent variable is continuous instead of categorical and we assume that it is from a normal distribution. The EM algorithm is used to obtain the estimates of the parameter we are interested in and Gauss–Hermite quadrature is used to approximate the integration of the latent variable. The standard errors of the parameter estimates can be obtained from the bootstrap method or from the inverse of the Fisher information matrix of the final marginal likelihood. Comparisons are made to the mixed model and complete-case analysis in terms of a clinical trial dataset, which is Weight Gain Prevention among Women (WGPW) study. We use the generalized Pearson residuals to assess the fit of the proposed latent variable model.     

Sparse cluster analysis of large-scale discrete variables with application to single nucleotide polymorphism data

Currently, extreme large-scale genetic data present significant challenges for cluster analysis. Most of the existing clustering methods are typically built on the Euclidean distance and geared toward analyzing continuous response. They work well for clustering, e.g. microarray gene expression data, but often perform poorly for clustering, e.g. large-scale single nucleotide polymorphism (SNP) data. In this paper, we study the penalized latent class model for clustering extremely large-scale discrete data. The penalized latent class model takes into account the discrete nature of the response using appropriate generalized linear models and adopts the lasso penalized likelihood approach for simultaneous model estimation and selection of important covariates. We develop very efficient numerical algorithms for model estimation based on the iterative coordinate descent approach and further develop the expectation–maximization algorithm to incorporate and model missing values. We use simulation studies and applications to the international HapMap SNP data to illustrate the competitive performance of the penalized latent class model.     

State-space models for multivariate longitudinal data of mixed types

We propose a class of state-space models for multivariate longitudinal data where the components of the response vector may have different distributions. The approach is based on the class of Tweedie exponential dispersion models, which accommodates a wide variety of discrete, continuous and mixed data. The latent process is assumed to be a Markov process, and the observations are conditionally independent given the latent process, over time as well as over the components of the response vector. This provides a fully parametric alternative to the quasilikelihood approach of Liang and Zeger. We estimate the regression parameters for time-varying covariates entering either via the observation model or via the latent process, based on an estimating equation derived from the Kalman smoother. We also consider analysis of residuals from both the observation model and the latent process.     

Mixture of latent trait analyzers for model-based clustering of categorical data

Model-based clustering methods for continuous data are well established and commonly used in a wide range of applications. However, model-based clustering methods for categorical data are less standard. Latent class analysis is a commonly used method for model-based clustering of binary data and/or categorical data, but due to an assumed local independence structure there may not be a correspondence between the estimated latent classes and groups in the population of interest. The mixture of latent trait analyzers model extends latent class analysis by assuming a model for the categorical response variables that depends on both a categorical latent class and a continuous latent trait variable; the discrete latent class accommodates group structure and the continuous latent trait accommodates dependence within these groups. Fitting the mixture of latent trait analyzers model is potentially difficult because the likelihood function involves an integral that cannot be evaluated analytically. We develop a variational approach for fitting the mixture of latent trait models and this provides an efficient model fitting strategy. The mixture of latent trait analyzers model is demonstrated on the analysis of data from the National Long Term Care Survey (NLTCS) and voting in the U.S. Congress. The model is shown to yield intuitive clustering results and it gives a much better fit than either latent class analysis or latent trait analysis alone.     

A Class of Multidimensional Latent Class IRT Models for Ordinal Polytomous Item Responses

We propose a class of multidimensional Item Response Theory models for polytomously-scored items with ordinal response categories. This class extends an existing class of multidimensional models for dichotomously-scored items in which the latent abilities are represented by a random vector assumed to have a discrete distribution, with support points corresponding to different latent classes in the population. In the proposed approach, we allow for different parameterizations for the conditional distribution of the response variables given the latent traits, which depend on the type of link function and the constraints imposed on the item parameters. Moreover, we suggest a strategy for model selection that is based on a series of steps consisting of selecting specific features, such as the dimension of the model (number of latent traits), the number of latent classes, and the specific parameterization. In order to illustrate the proposed approach, we analyze a dataset from a study on anxiety and depression on a sample of oncological patients.     

The beta distribution as a latent response model for ordinal data (I): Estimation of location and dispersion parameters

Ordinal data are often modeled using a continuous latent response distribution, which is partially observed through windows of adjacent intervals defined by cutpoints. In this paper we propose the beta distribution as a model for the latent response. The beta distribution has several advantages over the other common distributions used, e.g. , normal and logistic. In particular, it enables separate modeling of location and dispersion effects which is essential in the Taguchi method of robust design. First, we study the problem of estimating the location and dispersion parameters of a single beta distribution (representing a single treatment) from ordinal data assuming known equispaced cutpoints. Two methods of estimation are compared: the maximum likelihood method and the method of moments. Two methods of treating the data are considered: in raw discrete form and in smoothed continuousized form. A large scale simulation study is carried out to compare the different methods. The mean square errors of the estimates are obtained under a variety of parameter configurations. Comparisons are made based on the ratios of the mean square errors (called the relative efficiencies). No method is universally the best, but the maximum likelihood method using continuousized data is found to perform generally well, especially for estimating the dispersion parameter. This method is also computationally much faster than the other methods and does not experience convergence difficulties in case of sparse or empty cells. Next, the problem of estimating unknown cutpoints is addressed. Here the multiple treatments setup is considered since in an actual application, cutpoints are common to all treatments, and must be estimated from all the data. A two-step iterative algorithm is proposed for estimating the location and dispersion parameters of the treatments, and the cutpoints. The proposed beta model and McCullagh's (1980) proportional odds model are compared by fitting them to two real data sets.     

A graphical evaluation of logistic ridge estimator in mixture experiments

In comparison to other experimental studies, multicollinearity appears frequently in mixture experiments, a special study area of response surface methodology, due to the constraints on the components composing the mixture. In the analysis of mixture experiments by using a special generalized linear model, logistic regression model, multicollinearity causes precision problems in the maximum-likelihood logistic regression estimate. Therefore, effects due to multicollinearity can be reduced to a certain extent by using alternative approaches. One of these approaches is to use biased estimators for the estimation of the coefficients. In this paper, we suggest the use of logistic ridge regression (RR) estimator in the cases where there is multicollinearity during the analysis of mixture experiments using logistic regression. Also, for the selection of the biasing parameter, we use fraction of design space plots for evaluating the effect of the logistic RR estimator with respect to the scaled mean squared error of prediction. The suggested graphical approaches are illustrated on the tumor incidence data set.     

The Analysis of Methadone Clinic Data Using Marginal and Conditional Logistic Models with Mixture or Random Effects

The paper develops methods for the statistical analysis of outcomes of methadone maintenance treatment (MMT). Subjects for this study were a cohort of patients entering MMT in Sydney in 1986. Urine drug tests on these subjects were performed weekly during MMT, and were reported as either positive or negative for morphine, the marker of recent heroin use. To allow correlation between the repeated binary measurements, a marginal logistic model was fitted using the generalized estimating equation (GEE) approach and the alternating logistic regression approach. Conditional logistic models are also considered. Results of separate fitting to each patient and score tests suggest that there is substantial between-patient variation in response to MMT. To account for the population heterogeneity and to facilitate subject-specific inference, the conditional logistic model is extended by introducing random intercepts. The two, three and four group mixture models are also investigated. The model of best fit is a three group mixture model, in which about a quarter of the subjects have a poor response to MMT, with continued heroin use independent of daily dose of methadone; about a quarter of the subjects have a very good response, with little or no heroin use, again independent of dose; and about half the subjects responded in a dose-dependent fashion, with reduced heroin use while receiving higher doses of methadone. These findings are consistent with clinical experience. There is also an association between reduced drug use and increased duration in treatment. The mixture model is recommended since it is quite tractable in terms of estimation and model selection as well as being supported by clinical experience.     

A Two-Latent-Class Model for Smoking Cessation Data with Informative Dropouts

Non ignorable missing data is a common problem in longitudinal studies. Latent class models are attractive for simplifying the modeling of missing data when the data are subject to either a monotone or intermittent missing data pattern. In our study, we propose a new two-latent-class model for categorical data with informative dropouts, dividing the observed data into two latent classes; one class in which the outcomes are deterministic and a second one in which the outcomes can be modeled using logistic regression. In the model, the latent classes connect the longitudinal responses and the missingness process under the assumption of conditional independence. Parameters are estimated by the method of maximum likelihood estimation based on the above assumptions and the tetrachoric correlation between responses within the same subject. We compare the proposed method with the shared parameter model and the weighted GEE model using the areas under the ROC curves in the simulations and the application to the smoking cessation data set. The simulation results indicate that the proposed two-latent-class model performs well under different missing procedures. The application results show that our proposed method is better than the shared parameter model and the weighted GEE model.     

Approximating cross-validatory predictive evaluation in Bayesian latent variable models with integrated IS and WAIC

Looking at predictive accuracy is a traditional method for comparing models. A natural method for approximating out-of-sample predictive accuracy is leave-one-out cross-validation (LOOCV)—we alternately hold out each case from a full dataset and then train a Bayesian model using Markov chain Monte Carlo without the held-out case; at last we evaluate the posterior predictive distribution of all cases with their actual observations. However, actual LOOCV is time-consuming. This paper introduces two methods, namely iIS and iWAIC, for approximating LOOCV with only Markov chain samples simulated from a posterior based on a full dataset. iIS and iWAIC aim at improving the approximations given by importance sampling (IS) and WAIC in Bayesian models with possibly correlated latent variables. In iIS and iWAIC, we first integrate the predictive density over the distribution of the latent variables associated with the held-out without reference to its observation, then apply IS and WAIC approximations to the integrated predictive density. We compare iIS and iWAIC with other approximation methods in three kinds of models: finite mixture models, models with correlated spatial effects, and a random effect logistic regression model. Our empirical results show that iIS and iWAIC give substantially better approximates than non-integrated IS and WAIC and other methods.     

Elite players’ perceptions of football playing surfaces: a mixed effects ordinal logistic regression model of players’ perceptions

The aim of this study was to determine potential explanatory factors that may be associated with different attitudes amongst the global population of elite footballers to the use of different surfaces for football. A questionnaire was used to capture elite football players’ perceptions of playing surfaces and a mixed effects ordinal logistic regression model was used to explore potential explanatory factors of players’ perceptions. In total, responses from 1129 players from 44 different countries were analysed. The majority of players expressed a strong preference for the use of Natural Turf pitches over alternatives such as Artificial Turf. The regression model, with a players’ country as a random effect, indicated that players were less favourable towards either Natural Turf or Artificial Turf where there was perceived to be greater variability in surface qualities or the surface was perceived to have less desirable properties. Player’s surface experience was also linked to their overall attitudes, with a suggestion that the quality of the Natural Turf surface players experienced dictated players’ support for Artificial Turf.     

Bayesian estimation in the multidimensional three-parameter logistic model

The Gibbs sampler has a great potential to be an efficient and versatile estimation procedure in item response theory. In this article, based on a data augmentation scheme using the Gibbs sampler, we propose a Bayesian procedure to estimate the multidimensional three-parameter logistic model. With the introduction of the two latent variables, the full conditional distributions are tractable, and consequently the Gibbs sampling is easy to implement. Finally, the technique is illustrated by using simulated and real data, respectively.     

Latent class based multiple imputation approach for missing categorical data

In this paper we propose a latent class based multiple imputation approach for analyzing missing categorical covariate data in a highly stratified data model. In this approach, we impute the missing data assuming a latent class imputation model and we use likelihood methods to analyze the imputed data. Via extensive simulations, we study its statistical properties and make comparisons with complete case analysis, multiple imputation, saturated log-linear multiple imputation and the Expectation–Maximization approach under seven missing data mechanisms (including missing completely at random, missing at random and not missing at random). These methods are compared with respect to bias, asymptotic standard error, type I error, and 95% coverage probabilities of parameter estimates. Simulations show that, under many missingness scenarios, latent class multiple imputation performs favorably when jointly considering these criteria. A data example from a matched case–control study of the association between multiple myeloma and polymorphisms of the Inter-Leukin 6 genes is considered.     

Multilevel models for longitudinal data

Summary.  Repeated measures and repeated events data have a hierarchical structure which can be analysed by using multilevel models. A growth curve model is an example of a multilevel random-coefficients model, whereas a discrete time event history model for recurrent events can be fitted as a multilevel logistic regression model. The paper describes extensions to the basic growth curve model to handle auto-correlated residuals, multiple-indicator latent variables and correlated growth processes, and event history models for correlated event processes. The multilevel approach to the analysis of repeated measures data is contrasted with structural equation modelling. The methods are illustrated in analyses of children's growth, changes in social and political attitudes, and the interrelationship between partnership transitions and childbearing.     

Identifying predictors of violent behaviour among students using the conventional logistic and multilevel logistic models

Analysing individual-, school- and class-level observations is a good and efficient approach in epidemiologic research. Using data on violent behaviour among secondary school students we compared results from the conventional logistic modelling with multilevel logistic modelling approach using the gllamm command in Stata. We illustrated the advantage of multilevel modelling over the conventional logistic modelling through an example of data from violence experience among secondary school students. We constructed a logistic model with a random intercept on the school and class levels to account for unexplained heterogeneity between schools and classes. In the multilevel model, we estimated that, in an average school, the odds of experiencing violence are 3 (OR=2.99, 95% CI: 1.86, 4.81, p<0.0001) times higher for students who use drugs as opposed to the odds of experiencing violence for students who do not use drugs. However, the estimates in the conventional logistic model are slightly lower.

We estimated that a normally distributed random intercept for schools and classes that accounts for any unexplained heterogeneity between schools and classes has variances 0.017 and 0.035, respectively. We therefore recommend the multilevel logistic modelling when data are clustered.     

On power and sample size calculations for Wald tests in generalized linear models

A Wald test-based approach for power and sample size calculations has been presented recently for logistic and Poisson regression models using the asymptotic normal distribution of the maximum likelihood estimator, which is applicable to tests of a single parameter. Unlike the previous procedures involving the use of score and likelihood ratio statistics, there is no simple and direct extension of this approach for tests of more than a single parameter. In this article, we present a method for computing sample size and statistical power employing the discrepancy between the noncentral and central chi-square approximations to the distribution of the Wald statistic with unrestricted and restricted parameter estimates, respectively. The distinguishing features of the proposed approach are the accommodation of tests about multiple parameters, the flexibility of covariate configurations and the generality of overall response levels within the framework of generalized linear models. The general procedure is illustrated with some special situations that have motivated this research. Monte Carlo simulation studies are conducted to assess and compare its accuracy with existing approaches under several model specifications and covariate distributions.     

Joint analysis of nonlinear heterogeneous longitudinal data and binary outcome: an application to AIDS clinical studies

Finite mixture models are currently used to analyze heterogeneous longitudinal data. By releasing the homogeneity restriction of nonlinear mixed-effects (NLME) models, finite mixture models not only can estimate model parameters but also cluster individuals into one of the pre-specified classes with class membership probabilities. This clustering may have clinical significance, which might be associated with a clinically important binary outcome. This article develops a joint modeling of a finite mixture of NLME models for longitudinal data in the presence of covariate measurement errors and a logistic regression for a binary outcome, linked by individual latent class indicators, under a Bayesian framework. Simulation studies are conducted to assess the performance of the proposed joint model and a naive two-step model, in which finite mixture model and logistic regression are fitted separately, followed by an application to a real data set from an AIDS clinical trial, in which the viral dynamics and dichotomized time to the first decline of CD4/CD8 ratio are analyzed jointly.