Joint modeling of mixed skewed continuous and ordinal longitudinal responses: a Bayesian approach

In this paper, a joint model for analyzing multivariate mixed ordinal and continuous responses, where continuous outcomes may be skew, is presented. For modeling the discrete ordinal responses, a continuous latent variable approach is considered and for describing continuous responses, a skew-normal mixed effects model is used. A Bayesian approach using Markov Chain Monte Carlo (MCMC) is adopted for parameter estimation. Some simulation studies are performed for illustration of the proposed approach. The results of the simulation studies show that the use of the separate models or the normal distributional assumption for shared random effects and within-subject errors of continuous and ordinal variables, instead of the joint modeling under a skew-normal distribution, leads to biased parameter estimates. The approach is used for analyzing a part of the British Household Panel Survey (BHPS) data set. Annual income and life satisfaction are considered as the continuous and the ordinal longitudinal responses, respectively. The annual income variable is severely skewed, therefore, the use of the normality assumption for the continuous response does not yield acceptable results. The results of data analysis show that gender, marital status, educational levels and the amount of money spent on leisure have a significant effect on annual income, while marital status has the highest impact on life satisfaction.     

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.     

Model-based clustering of Gaussian copulas for mixed data

Clustering of mixed data is important yet challenging due to a shortage of conventional distributions for such data. In this article, we propose a mixture model of Gaussian copulas for clustering mixed data. Indeed copulas, and Gaussian copulas in particular, are powerful tools for easily modeling the distribution of multivariate variables. This model clusters data sets with continuous, integer, and ordinal variables (all having a cumulative distribution function) by considering the intra-component dependencies in a similar way to the Gaussian mixture. Indeed, each component of the Gaussian copula mixture produces a correlation coefficient for each pair of variables and its univariate margins follow standard distributions (Gaussian, Poisson, and ordered multinomial) depending on the nature of the variable (continuous, integer, or ordinal). As an interesting by-product, this model generalizes many well-known approaches and provides tools for visualization based on its parameters. The Bayesian inference is achieved with a Metropolis-within-Gibbs sampler. The numerical experiments, on simulated and real data, illustrate the benefits of the proposed model: flexible and meaningful parameterization combined with visualization features.     

A distance-based rounding strategy for post-imputation ordinal data

Multiple imputation has emerged as a widely used model-based approach in dealing with incomplete data in many application areas. Gaussian and log-linear imputation models are fairly straightforward to implement for continuous and discrete data, respectively. However, in missing data settings which include a mix of continuous and discrete variables, correct specification of the imputation model could be a daunting task owing to the lack of flexible models for the joint distribution of variables of different nature. This complication, along with accessibility to software packages that are capable of carrying out multiple imputation under the assumption of joint multivariate normality, appears to encourage applied researchers for pragmatically treating the discrete variables as continuous for imputation purposes, and subsequently rounding the imputed values to the nearest observed category. In this article, I introduce a distance-based rounding approach for ordinal variables in the presence of continuous ones. The first step of the proposed rounding process is predicated upon creating indicator variables that correspond to the ordinal levels, followed by jointly imputing all variables under the assumption of multivariate normality. The imputed values are then converted to the ordinal scale based on their Euclidean distances to a set of indicators, with minimal distance corresponding to the closest match. I compare the performance of this technique to crude rounding via commonly accepted accuracy and precision measures with simulated data sets.     

A Bayesian test of homogeneity of association parameter using transition modelling of longitudinal mixed responses

In this paper, a Bayesian framework using a joint transition model for analysing longitudinal mixed ordinal and continuous responses is considered. The joint model considers a multivariate mixed model for the responses in which a transitive cumulative logistic regression model and an autoregressive regression model are used to model ordinal and continuous responses, respectively. Also, to take into account the association between longitudinal ordinal and continuous responses, a dynamic association parameter is used. A test is conducted to see whether this parameter is time-invariant and another test is presented to see whether this parameter is equal to zero or significantly far from zero. Our approach is applied to longitudinal PIAT (Peabody Individual Achievement Test) data where the Bayesian estimates of parameters are obtained.     

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.     

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.     

A stochastic variant of the EM algorithm to fit mixed (discrete and continuous) longitudinal data with nonignorable missingness

Abstract

In longitudinal studies data are collected on the same set of units for more than one occasion. In medical studies it is very common to have mixed Poisson and continuous longitudinal data. In such studies, for different reasons, some intended measurements might not be available resulting in a missing data setting. When the probability of missingness is related to the missing values, the missingness mechanism is termed nonrandom. The stochastic expectation-maximization (SEM) algorithm and the parametric fractional imputation (PFI) method are developed to handle nonrandom missingness in mixed discrete and continuous longitudinal data assuming different covariance structures for the continuous outcome. The proposed techniques are evaluated using simulation studies. Also, the proposed techniques are applied to the interstitial cystitis data base (ICDB) data.     

AN APPROACH FOR JOINTLY MODELING MULTIVARIATE LONGITUDINAL MEASUREMENTS AND DISCRETE TIME-TO-EVENT DATA

In many medical studies, patients are followed longitudinally and interest is on assessing the relationship between longitudinal measurements and time to an event. Recently, various authors have proposed joint modeling approaches for longitudinal and time-to-event data for a single longitudinal variable. These joint modeling approaches become intractable with even a few longitudinal variables. In this paper we propose a regression calibration approach for jointly modeling multiple longitudinal measurements and discrete time-to-event data. Ideally, a two-stage modeling approach could be applied in which the multiple longitudinal measurements are modeled in the first stage and the longitudinal model is related to the time-to-event data in the second stage. Biased parameter estimation due to informative dropout makes this direct two-stage modeling approach problematic. We propose a regression calibration approach which appropriately accounts for informative dropout. We approximate the conditional distribution of the multiple longitudinal measurements given the event time by modeling all pairwise combinations of the longitudinal measurements using a bivariate linear mixed model which conditions on the event time. Complete data are then simulated based on estimates from these pairwise conditional models, and regression calibration is used to estimate the relationship between longitudinal data and time-to-event data using the complete data. We show that this approach performs well in estimating the relationship between multivariate longitudinal measurements and the time-to-event data and in estimating the parameters of the multiple longitudinal process subject to informative dropout. We illustrate this methodology with simulations and with an analysis of primary biliary cirrhosis (PBC) data.     

A Semiparametric Bayesian Approach to Multivariate Longitudinal Data

We extend the standard multivariate mixed model by incorporating a smooth time effect and relaxing distributional assumptions. We propose a semiparametric Bayesian approach to multivariate longitudinal data using a mixture of Polya trees prior distribution. Usually, the distribution of random effects in a longitudinal data model is assumed to be Gaussian. However, the normality assumption may be suspect, particularly if the estimated longitudinal trajectory parameters exhibit multimodality and skewness. In this paper we propose a mixture of Polya trees prior density to address the limitations of the parametric random effects distribution. We illustrate the methodology by analyzing data from a recent HIV-AIDS study.     

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.     

Sensitivity analysis for the identifiability with application to latent random effect model for the mixed data

In this paper, we study the indentifiability of a latent random effect model for the mixed correlated continuous and ordinal longitudinal responses. We derive conditions for the identifiability of the covariance parameters of the responses. Also, we proposed sensitivity analysis to investigate the perturbation from the non-identifiability of the covariance parameters, it is shown how one can use some elements of covariance structure. These elements associate conditions for identifiability of the covariance parameters of the responses. Influence of small perturbation of these elements on maximal normal curvature is also studied. The model is illustrated using medical data.     

A Simulation Study Comparing Multiple Imputation Methods for Incomplete Longitudinal Ordinal Data

Multiple imputation (MI) is now a reference solution for handling missing data. The default method for MI is the Multivariate Normal Imputation (MNI) algorithm that is based on the multivariate normal distribution. In the presence of longitudinal ordinal missing data, where the Gaussian assumption is no longer valid, application of the MNI method is questionable. This simulation study compares the performance of the MNI and ordinal imputation regression model for incomplete longitudinal ordinal data for situations covering various numbers of categories of the ordinal outcome, time occasions, sample sizes, rates of missingness, well-balanced, and skewed data.     

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.     

A latent variable model for analyzing mixed longitudinal (k,l)-inflated count and ordinal responses

A random effects model for analyzing mixed longitudinal count and ordinal data is presented where the count response is inflated in two points (k and l) and an (k,l)-Inflated Power series distribution is used as its distribution. A full likelihood-based approach is used to obtain maximum likelihood estimates of parameters of the model. For data with non-ignorable missing values models with probit model for missing mechanism are used.The dependence between longitudinal sequences of responses and inflation parameters are investigated using a random effects approach. Also, to investigate the correlation between mixed ordinal and count responses of each individuals at each time, a shared random effect is used. In order to assess the performance of the model, a simulation study is performed for a case that the count response has (k,l)-Inflated Binomial distribution. Performance comparisons of count-ordinal random effect model, Zero-Inflated ordinal random effects model and (k,l)-Inflated ordinal random effects model are also given. The model is applied to a real social data set from the first two waves of the national longitudinal study of adolescent to adult health (Add Health study). In this data set, the joint responses are the number of days in a month that each individual smoked as the count response and the general health condition of each individual as the ordinal response. For the count response there is incidence of excess values of 0 and 30.     

Mixed Correlated Bivariate Ordinal and Negative Binomial Longitudinal Responses with Nonignorable Missing Values

Regression models with random effects are proposed for joint analysis of negative binomial and ordinal longitudinal data with nonignorable missing values under fully parametric framework. The presented model simultaneously considers a multivariate probit regression model for the missing mechanisms, which provides the ability of examining the missing data assumptions and a multivariate mixed model for the responses. Random effects are used to take into account the correlation between longitudinal responses of the same individual. A full likelihood-based approach that allows yielding maximum likelihood estimates of the model parameters is used. The model is applied to a medical data, obtained from an observational study on women, where the correlated responses are the ordinal response of osteoporosis of the spine and negative binomial response is the number of joint damage. A sensitivity of the results to the assumptions is also investigated. The effect of some covariates on all responses are investigated simultaneously.     

A mixture latent variable model for modeling mixed data in heterogeneous populations and its applications

Latent variable models are widely used for jointly modeling of mixed data including nominal, ordinal, count and continuous data. In this paper, we consider a latent variable model for jointly modeling relationships between mixed binary, count and continuous variables with some observed covariates. We assume that, given a latent variable, mixed variables of interest are independent and count and continuous variables have Poisson distribution and normal distribution, respectively. As such data may be extracted from different subpopulations, consideration of an unobserved heterogeneity has to be taken into account. A mixture distribution is considered (for the distribution of the latent variable) which accounts the heterogeneity. The generalized EM algorithm which uses the Newton–Raphson algorithm inside the EM algorithm is used to compute the maximum likelihood estimates of parameters. The standard errors of the maximum likelihood estimates are computed by using the supplemented EM algorithm. Analysis of the primary biliary cirrhosis data is presented as an application of the proposed model.     

Multivariate Dispersion Models Generated From Gaussian Copula

In this paper a class of multivariate dispersion models generated from the multivariate Gaussian copula is presented. Being a multivariate extension of Jørgensen's (1987a) dispersion models, this class of multivariate models is parametrized by marginal position, dispersion and dependence parameters, producing a large variety of multivariate discrete and continuous models including the multivariate normal as a special case. Properties of the multivariate distributions are investigated, some of which are similar to those of the multivariate normal distribution, which makes these models potentially useful for the analysis of correlated non-normal data in a way analogous to that of multivariate normal data. As an example, we illustrate an application of the models to the regression analysis of longitudinal data, and establish an asymptotic relationship between the likelihood equation and the generalized estimating equation of Liang & Zeger (1986).     

An Appraisal of Methods for the Analysis of Longitudinal Ordinal Response Data with Random Dropout Using a Nonhomogeneous Markov Model

There are many methods for analyzing longitudinal ordinal response data with random dropout. These include maximum likelihood (ML), weighted estimating equations (WEEs), and multiple imputations (MI). In this article, using a Markov model where the effect of previous response on the current response is investigated as an ordinal variable, the likelihood is partitioned to simplify the use of existing software. Simulated data, generated to present a three-period longitudinal study with random dropout, are used to compare performance of ML, WEE, and MI methods in terms of standardized bias and coverage probabilities. These estimation methods are applied to a real medical data set.     

Spatial analysis of auto-multivariate lattice data

Most problems related to environmental studies are innately multivariate. In fact, in each spatial location more than one variable is usually measured. In geostatistics multivariate data analysis, where we intend to predict the value of a random vector in a new site, which has no data, cokriging method is used as the best linear unbiased prediction. In lattice data analysis, where almost exclusively the probability modeling of data is of concern, only auto-Gaussian model has been used for continuous multivariate data. For discrete multivariate data little work has been carried out. In this paper, an auto-multinomial model is suggested for analyzing multivariate lattice discrete data. The proposed method is illustrated by a real example of air pollution in Tehran, Iran.