Random coefficient models for binary longitudinal responses with attrition

We extend the approach introduced by Aitkin and Alfò (1998, Statistics and Computing, 4, pp. 289–307) to the general framework of random coefficient models and propose a class of conditional models to deal with binary longitudinal responses, including unknown sources of heterogeneity in the regression parameters as well as serial dependence of Markovian form.Furthermore, we discuss the extension of the proposed approach to the analysis of informative drop-outs, which represent a central problem in longitudinal studies, and define, as suggested by Follmann and Wu (1995, Biometrics, 51, pp. 151–168), a conditional specification of the full shared parameter model for the primary response and the missingness indicator. The model is applied to a dataset from a methadone maintenance treatment programme held in Sydney in 1986 and previously analysed by Chan et al. (1998, Australian & New Zealand Journal of Statistics, 40, pp. 1–10).All of the proposed models are estimated by means of an EM algorithm for nonparametric maximum likelihood, without assuming any specific parametric distribution for the random coefficients and for the drop-out process.A small scale simulation work is described to explore the behaviour of the extended approach in a number of different situations where informative drop-outs are present.     

Variance component models for longitudinal count data with baseline information: epilepsy data revisited

Random effect models have often been used in longitudinal data analysis since they allow for association among repeated measurements due to unobserved heterogeneity. Various approaches have been proposed to extend mixed models for repeated count data to include dependence on baseline counts. Dependence between baseline counts and individual-specific random effects result in a complex form of the (conditional) likelihood. An approximate solution can be achieved ignoring this dependence, but this approach could result in biased parameter estimates and in wrong inferences. We propose a computationally feasible approach to overcome this problem, leaving the random effect distribution unspecified. In this context, we show how the EM algorithm for nonparametric maximum likelihood (NPML) can be extended to deal with dependence of repeated measures on baseline counts.     

Marginalized transition random effect models for multivariate longitudinal binary data

Generalized linear models with random effects and/or serial dependence are commonly used to analyze longitudinal data. However, the computation and interpretation of marginal covariate effects can be difficult. This led Heagerty (1999, 2002) to propose models for longitudinal binary data in which a logistic regression is first used to explain the average marginal response. The model is then completed by introducing a conditional regression that allows for the longitudinal, within‐subject, dependence, either via random effects or regressing on previous responses. In this paper, the authors extend the work of Heagerty to handle multivariate longitudinal binary response data using a triple of regression models that directly model the marginal mean response while taking into account dependence across time and across responses. Markov Chain Monte Carlo methods are used for inference. Data from the Iowa Youth and Families Project are used to illustrate the methods.     

Prediction of transplant-free survival in idiopathic pulmonary fibrosis patients using joint models for event times and mixed multivariate longitudinal data

We implement a joint model for mixed multivariate longitudinal measurements, applied to the prediction of time until lung transplant or death in idiopathic pulmonary fibrosis. Specifically, we formulate a unified Bayesian joint model for the mixed longitudinal responses and time-to-event outcomes. For the longitudinal model of continuous and binary responses, we investigate multivariate generalized linear mixed models using shared random effects. Longitudinal and time-to-event data are assumed to be independent conditional on available covariates and shared parameters. A Markov chain Monte Carlo algorithm, implemented in OpenBUGS, is used for parameter estimation. To illustrate practical considerations in choosing a final model, we fit 37 different candidate models using all possible combinations of random effects and employ a deviance information criterion to select a best-fitting model. We demonstrate the prediction of future event probabilities within a fixed time interval for patients utilizing baseline data, post-baseline longitudinal responses, and the time-to-event outcome. The performance of our joint model is also evaluated in simulation studies.     

Linear quantile mixed models

Dependent data arise in many studies. Frequently adopted sampling designs, such as cluster, multilevel, spatial, and repeated measures, may induce this dependence, which the analysis of the data needs to take into due account. In a previous publication (Geraci and Bottai in Biostatistics 8:140–154, 2007), we proposed a conditional quantile regression model for continuous responses where subject-specific random intercepts were included to account for within-subject dependence in the context of longitudinal data analysis. The approach hinged upon the link existing between the minimization of weighted absolute deviations, typically used in quantile regression, and the maximization of a Laplace likelihood. Here, we consider an extension of those models to more complex dependence structures in the data, which are modeled by including multiple random effects in the linear conditional quantile functions. We also discuss estimation strategies to reduce the computational burden and inefficiency associated with the Monte Carlo EM algorithm we have proposed previously. In particular, the estimation of the fixed regression coefficients and of the random effects’ covariance matrix is based on a combination of Gaussian quadrature approximations and non-smooth optimization algorithms. Finally, a simulation study and a number of applications of our models are presented.     

Estimation of a Semiparametric Recursive Bivariate Probit Model with Nonparametric Mixing

We consider an extension of the recursive bivariate probit model for estimating the effect of a binary variable on a binary outcome in the presence of unobserved confounders, nonlinear covariate effects and overdispersion. Specifically, the model consists of a system of two binary outcomes with a binary endogenous regressor which includes smooth functions of covariates, hence allowing for flexible functional dependence of the responses on the continuous regressors, and arbitrary random intercepts to deal with overdispersion arising from correlated observations on clusters or from the omission of non‐confounding covariates. We fit the model by maximizing a penalized likelihood using an Expectation‐Maximisation algorithm. The issues of automatic multiple smoothing parameter selection and inference are also addressed. The empirical properties of the proposed algorithm are examined in a simulation study. The method is then illustrated using data from a survey on health, aging and wealth.     

A generalized linear mixed model for longitudinal binary data with a marginal logit link function

Longitudinal studies of a binary outcome are common in the health, social, and behavioral sciences. In general, a feature of random effects logistic regression models for longitudinal binary data is that the marginal functional form, when integrated over the distribution of the random effects, is no longer of logistic form. Recently, Wang and Louis (2003) proposed a random intercept model in the clustered binary data setting where the marginal model has a logistic form. An acknowledged limitation of their model is that it allows only a single random effect that varies from cluster to cluster. In this paper, we propose a modification of their model to handle longitudinal data, allowing separate, but correlated, random intercepts at each measurement occasion. The proposed model allows for a flexible correlation structure among the random intercepts, where the correlations can be interpreted in terms of Kendall's τ. For example, the marginal correlations among the repeated binary outcomes can decline with increasing time separation, while the model retains the property of having matching conditional and marginal logit link functions. Finally, the proposed method is used to analyze data from a longitudinal study designed to monitor cardiac abnormalities in children born to HIV-infected women.     

Most Likely Transformations

We propose and study properties of maximum likelihood estimators in the class of conditional transformation models. Based on a suitable explicit parameterization of the unconditional or conditional transformation function, we establish a cascade of increasingly complex transformation models that can be estimated, compared and analysed in the maximum likelihood framework. Models for the unconditional or conditional distribution function of any univariate response variable can be set up and estimated in the same theoretical and computational framework simply by choosing an appropriate transformation function and parameterization thereof. The ability to evaluate the distribution function directly allows us to estimate models based on the exact likelihood, especially in the presence of random censoring or truncation. For discrete and continuous responses, we establish the asymptotic normality of the proposed estimators. A reference software implementation of maximum likelihood‐based estimation for conditional transformation models that allows the same flexibility as the theory developed here was employed to illustrate the wide range of possible applications.     

A Bayesian shared parameter model for joint modeling of longitudinal continuous and binary outcomes

Joint modeling of associated mixed biomarkers in longitudinal studies leads to a better clinical decision by improving the efficiency of parameter estimates. In many clinical studies, the observed time for two biomarkers may not be equivalent and one of the longitudinal responses may have recorded in a longer time than the other one. In addition, the response variables may have different missing patterns. In this paper, we propose a new joint model of associated continuous and binary responses by accounting different missing patterns for two longitudinal outcomes. A conditional model for joint modeling of the two responses is used and two shared random effects models are considered for intermittent missingness of two responses. A Bayesian approach using Markov Chain Monte Carlo (MCMC) is adopted for parameter estimation and model implementation. The validation and performance of the proposed model are investigated using some simulation studies. The proposed model is also applied for analyzing a real data set of bariatric surgery.     

Random effects regression models for count data with excess zeros in caries research

We extend the family of Poisson and negative binomial models to derive the joint distribution of clustered count outcomes with extra zeros. Two random effects models are formulated. The first model assumes a shared random effects term between the conditional probability of perfect zeros and the conditional mean of the imperfect state. The second formulation relaxes the shared random effects assumption by relating the conditional probability of perfect zeros and the conditional mean of the imperfect state to two different but correlated random effects variables. Under the conditional independence and the missing data at random assumption, a direct optimization of the marginal likelihood and an EM algorithm are proposed to fit the proposed models. Our proposed models are fitted to dental caries counts of children under the age of six in the city of Detroit.     

Adaptive likelihood estimator of conditional variance function

Modelling volatility in the form of conditional variance function has been a popular method mainly due to its application in financial risk management. Among others, we distinguish the parametric GARCH models and the nonparametric local polynomial approximation using weighted least squares or gaussian likelihood function. We introduce an alternative likelihood estimate of conditional variance and we show that substitution of the error density with its estimate yields similar asymptotic properties, that is, the proposed estimate is adaptive to the error distribution. Theoretical comparison with existing estimates reveals substantial gains in efficiency, especially if error distribution has fatter tails than Gaussian distribution. Simulated data confirm the theoretical findings while an empirical example demonstrates the gains of the proposed estimate.     

State space mixed models for longitudinal observations with binary and binomial responses

We propose a new class of state space models for longitudinal discrete response data where the observation equation is specified in an additive form involving both deterministic and random linear predictors. These models allow us to explicitly address the effects of trend, seasonal or other time-varying covariates while preserving the power of state space models in modeling serial dependence in the data. We develop a Markov chain Monte Carlo algorithm to carry out statistical inference for models with binary and binomial responses, in which we invoke de Jong and Shephard’s (Biometrika 82(2):339–350, 1995) simulation smoother to establish an efficient sampling procedure for the state variables. To quantify and control the sensitivity of posteriors on the priors of variance parameters, we add a signal-to-noise ratio type parameter in the specification of these priors. Finally, we illustrate the applicability of the proposed state space mixed models for longitudinal binomial response data in both simulation studies and data examples.     

Bayesian Analysis of Nonlinear Reproductive Dispersion Mixed Models for Longitudinal Data with Nonignorable Missing Covariates

This article proposes a Bayesian approach, which can simultaneously obtain the Bayesian estimates of unknown parameters and random effects, to analyze nonlinear reproductive dispersion mixed models (NRDMMs) for longitudinal data with nonignorable missing covariates and responses. The logistic regression model is employed to model the missing data mechanisms for missing covariates and responses. A hybrid sampling procedure combining the Gibber sampler and the Metropolis-Hastings algorithm is presented to draw observations from the conditional distributions. Because missing data mechanism is not testable, we develop the logarithm of the pseudo-marginal likelihood, deviance information criterion, the Bayes factor, and the pseudo-Bayes factor to compare several competing missing data mechanism models in the current considered NRDMMs with nonignorable missing covaraites and responses. Three simulation studies and a real example taken from the paediatric AIDS clinical trial group ACTG are used to illustrate the proposed methodologies. Empirical results show that our proposed methods are effective in selecting missing data mechanism models.     

Likelihood-based approach for analysis of longitudinal nominal data using marginalized random effects models

Likelihood-based marginalized models using random effects have become popular for analyzing longitudinal categorical data. These models permit direct interpretation of marginal mean parameters and characterize the serial dependence of longitudinal outcomes using random effects [12,22]. In this paper, we propose model that expands the use of previous models to accommodate longitudinal nominal data. Random effects using a new covariance matrix with a Kronecker product composition are used to explain serial and categorical dependence. The Quasi-Newton algorithm is developed for estimation. These proposed methods are illustrated with a real data set and compared with other standard methods.     

Generalised quasi‐likelihood inference in a semi‐parametric binary dynamic mixed logit model

There exists a recent study where dynamic mixed‐effects regression models for count data have been extended to a semi‐parametric context. However, when one deals with other discrete data such as binary responses, the results based on count data models are not directly applicable. In this paper, we therefore begin with existing binary dynamic mixed models and generalise them to the semi‐parametric context. For inference, we use a new semi‐parametric conditional quasi‐likelihood (SCQL) approach for the estimation of the non‐parametric function involved in the semi‐parametric model, and a semi‐parametric generalised quasi‐likelihood (SGQL) approach for the estimation of the main regression, dynamic dependence and random effects variance parameters. A semi‐parametric maximum likelihood (SML) approach is also used as a comparison to the SGQL approach. The properties of the estimators are examined both asymptotically and empirically. More specifically, the consistency of the estimators is established and finite sample performances of the estimators are examined through an intensive simulation study.     

Weighted empirical likelihood for generalized linear models with longitudinal data

In this paper, we introduce the empirical likelihood (EL) method to longitudinal studies. By considering the dependence within subjects in the auxiliary random vectors, we propose a new weighted empirical likelihood (WEL) inference for generalized linear models with longitudinal data. We show that the weighted empirical likelihood ratio always follows an asymptotically standard chi-squared distribution no matter which working weight matrix that we have chosen, but a well chosen working weight matrix can improve the efficiency of statistical inference. Simulations are conducted to demonstrate the accuracy and efficiency of our proposed WEL method, and a real data set is used to illustrate the proposed method.     

Mixture of linear mixed models using multivariate t distribution

Linear mixed models are widely used when multiple correlated measurements are made on each unit of interest. In many applications, the units may form several distinct clusters, and such heterogeneity can be more appropriately modelled by a finite mixture linear mixed model. The classical estimation approach, in which both the random effects and the error parts are assumed to follow normal distribution, is sensitive to outliers, and failure to accommodate outliers may greatly jeopardize the model estimation and inference. We propose a new mixture linear mixed model using multivariate t distribution. For each mixture component, we assume the response and the random effects jointly follow a multivariate t distribution, to conveniently robustify the estimation procedure. An efficient expectation conditional maximization algorithm is developed for conducting maximum likelihood estimation. The degrees of freedom parameters of the t distributions are chosen data adaptively, for achieving flexible trade-off between estimation robustness and efficiency. Simulation studies and an application on analysing lung growth longitudinal data showcase the efficacy of the proposed approach.     

A Bayesian conditional model for bivariate mixed ordinal and skew continuous longitudinal responses using quantile regression

In this paper, we develop a conditional model for analyzing mixed bivariate continuous and ordinal longitudinal responses. We propose a quantile regression model with random effects for analyzing continuous responses. For this purpose, an Asymmetric Laplace Distribution (ALD) is allocated for continuous response given random effects. For modeling ordinal responses, a cumulative logit model is used, via specifying a latent variable model, with considering other random effects. Therefore, the intra-association between continuous and ordinal responses is taken into account using their own exclusive random effects. But, the inter-association between two mixed responses is taken into account by adding a continuous response term in the ordinal model. We use a Bayesian approach via Markov chain Monte Carlo method for analyzing the proposed conditional model and to estimate unknown parameters, a Gibbs sampler algorithm is used. Moreover, we illustrate an application of the proposed model using a part of the British Household Panel Survey data set. The results of data analysis show that gender, age, marital status, educational level and the amount of money spent on leisure have significant effects on annual income. Also, the associated parameter is significant in using the best fitting proposed conditional model, thus it should be employed rather than analyzing separate models.     

Marginal and association regression models for longitudinal binary data with drop‐outs: A likelihood‐based approach

Longitudinal data often contain missing observations, and it is in general difficult to justify particular missing data mechanisms, whether random or not, that may be hard to distinguish. The authors describe a likelihood‐based approach to estimating both the mean response and association parameters for longitudinal binary data with drop‐outs. They specify marginal and dependence structures as regression models which link the responses to the covariates. They illustrate their approach using a data set from the Waterloo Smoking Prevention Project They also report the results of simulation studies carried out to assess the performance of their technique under various circumstances.