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.     

Frequentist and Bayesian approaches for a joint model for prostate cancer risk and longitudinal prostate-specific antigen data

The paper describes the use of frequentist and Bayesian shared-parameter joint models of longitudinal measurements of prostate-specific antigen (PSA) and the risk of prostate cancer (PCa). The motivating dataset corresponds to the screening arm of the Spanish branch of the European Randomized Screening for Prostate Cancer study. The results show that PSA is highly associated with the risk of being diagnosed with PCa and that there is an age-varying effect of PSA on PCa risk. Both the frequentist and Bayesian paradigms produced very close parameter estimates and subsequent 95% confidence and credibility intervals. Dynamic estimations of disease-free probabilities obtained using Bayesian inference highlight the potential of joint models to guide personalized risk-based screening strategies.     

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.     

Distance-based approach in univariate longitudinal data analysis

In this paper, we propose a methodology to analyze longitudinal data through distances between pairs of observations (or individuals) with regard to the explanatory variables used to fit continuous response variables. Restricted maximum-likelihood and generalized least squares are used to estimate the parameters in the model. We applied this new approach to study the effect of gender and exposure on the deviant behavior variable with respect to tolerance for a group of youths studied over a period of 5 years. Were performed simulations where we compared our distance-based method with classic longitudinal analysis with both AR(1) and compound symmetry correlation structures. We compared them under Akaike and Bayesian information criterions, and the relative efficiency of the generalized variance of the errors of each model. We found small gains in the proposed model fit with regard to the classical methodology, particularly in small samples, regardless of variance, correlation, autocorrelation structure and number of time measurements.     

A multilevel Bayesian model for contextual effect of material deprivation

The relationship between socioeconomic factors and health has been studied in many circumstances. Whether the association takes place at individual level only, or also at population level (contextual effect) is still unclear. We present a multilevel hierarchical Bayesian model to investigate the joint contribution of individual and population-based socioeconomic factors to mortality, using data from the census cohort of the general population of the city of Florence, Italy (Tuscany Longitudinal Study, 1991-1995). Evidence supporting a contextual effect of deprivation on mortality at the very fine level of aggregation is found. Inappropriate modelling of individual and aggregate variables could strongly bias effect estimates.Received: 10 January 2002, Revised: 23 June 2003, The research on Tuscany Longitudinal Study (Studio Longitudinale Toscano, SLTo) was supported by the Regione Toscana Servizio Statistica.     

An R package for model fitting,model selection and the simulation for longitudinal data with dropout missingness

Abstract

Missing data arise frequently in clinical and epidemiological fields, in particular in longitudinal studies. This paper describes the core features of an R package wgeesel, which implements marginal model fitting (i.e., weighted generalized estimating equations, WGEE; doubly robust GEE) for longitudinal data with dropouts under the assumption of missing at random. More importantly, this package comprehensively provide existing information criteria for WGEE model selection on marginal mean or correlation structures. Also, it can serve as a valuable tool for simulating longitudinal data with missing outcomes. Lastly, a real data example and simulations are presented to illustrate and validate our package.     

Stationary state space models for longitudinal data

The authors consider a class of state space models for the analysis of non‐normal longitudinal data whose latent process follows a stationary AR(1) model with exponential dispersion model margins. They propose to estimate parameters through an estimating equation approach based on the Kalman smoother. This allows them to carry out a straightforward analysis of a wide range of non‐normal data. They illustrate their approach via a simulation study and through analyses of Brazilian precipitation and US polio infection data.     

Variance function in regression analysis of longitudinal data using the generalized estimating equation approach

Longitudinal or clustered response data arise in many applications such as biostatistics, epidemiology and environmental studies. The repeated responses cannot in general be assumed to be independent. One method of analysing such data is by using the generalized estimating equations (GEE) approach. The current GEE method for estimating regression effects in longitudinal data focuses on the modelling of the working correlation matrix assuming a known variance function. However, correct choice of the correlation structure may not necessarily improve estimation efficiency for the regression parameters if the variance function is misspecified [Wang YG, Lin X. Effects of variance-function misspecification in analysis of longitudinal data. Biometrics. 2005;61:413–421]. In this connection two problems arise: finding a correct variance function and estimating the parameters of the chosen variance function. In this paper, we study the problem of estimating the parameters of the variance function assuming that the form of the variance function is known and then the effect of a misspecified variance function on the estimates of the regression parameters. We propose a GEE approach to estimate the parameters of the variance function. This estimation approach borrows the idea of Davidian and Carroll [Variance function estimation. J Amer Statist Assoc. 1987;82:1079–1091] by solving a nonlinear regression problem where residuals are regarded as the responses and the variance function is regarded as the regression function. A limited simulation study shows that the proposed method performs at least as well as the modified pseudo-likelihood approach developed by Wang and Zhao [A modified pseudolikelihood approach for analysis of longitudinal data. Biometrics. 2007;63:681–689]. Both these methods perform better than the GEE approach.     

Generalized linear mixed joint model for longitudinal and survival outcomes

Longitudinal studies often entail categorical outcomes as primary responses. When dropout occurs, non-ignorability is frequently accounted for through shared parameter models (SPMs). In this context, several extensions from Gaussian to non-Gaussian longitudinal processes have been proposed. In this paper, we formulate an approach for non-Gaussian longitudinal outcomes in the framework of joint models. As an extension of SPMs, based on shared latent effects, we assume that the history of the response up to current time may have an influence on the risk of dropout. This history is represented by the current, expected, value of the response. Since the time a subject spends in the study is continuous, we parametrize the dropout process through a proportional hazard model. The resulting model is referred to as Generalized Linear Mixed Joint Model (GLMJM). To estimate model parameters, we adopt a maximum likelihood approach via the EM algorithm. In this context, the maximization of the observed data log-likelihood requires numerical integration over the random effect posterior distribution, which is usually not straightforward; under the assumption of Gaussian random effects, we compare Gauss-Hermite and Pseudo-Adaptive Gaussian quadrature rules. We investigate in a simulation study the behaviour of parameter estimates in the case of Poisson and Binomial longitudinal responses, and apply the GLMJM to a benchmark dataset.     

A new formula for the computation of multivariate factorized moments by using the joint cumulative distribution function

This work presents a closed formula to compute any muitivariate factorized expected value from the knowledge of the joint cumulative distribution function (cdf) of any random variable. Additionally, a new nonparametric estimator alternative to the sample average is presented for the univariate case.     

GEE-based zero-inflated generalized Poisson model for clustered over or under-dispersed count data

The zero-inflated regression models such as zero-inflated Poisson (ZIP), zero-inflated negative binomial (ZINB) or zero-inflated generalized Poisson (ZIGP) regression models can model the count data with excess zeros. The ZINB model can handle over-dispersed and the ZIGP model can handle the over or under-dispersed count data with excess zeros as well. Moreover, the count data may be correlated because of data collection procedure or special study design. The clustered sampling approach is one of the examples in which the correlation among subjects could be defined. In such situations, a marginal model using generalized estimating equation (GEE) approach can incorporate these correlations and lead up to the relationships at the population level. In this study, the GEE-based zero-inflated generalized Poisson regression model was proposed to fit over and under-dispersed clustered count data with excess zeros.     

Modelling Correlated Zero-inflated Count Data

This paper extends the two-component approach to modelling count data with extra zeros, considered by Mullahy (1986), Heilbron (1994) and Welsh et al. (1996), to take account of possible serial dependence between repeated observations. Generalized estimating equations (Liang & Zeger, 1986) are constructed for each component of the model by incorporating correlation matrices into each of the maximum likelihood estimating equations. The proposed method is demonstrated on weekly counts of Noisy Friarbirds ( Philemon cornic-ulatus ), which were recorded by observers for the Canberra Garden Bird Survey (Hermes, 1981).     

A new four-parameter lifetime distribution

A new four-parameter distribution is introduced. It appears to be a distribution allowing for and only allowing for monotonically increasing, bathtub-shaped and upside down bathtub-shaped hazard rates. It contains as particular cases many of the known lifetime distributions. Some mathematical properties of the new distribution, including estimation procedures by the method of maximum likelihood are derived. Some simulations are run to assess the performance of the maximum-likelihood estimators. Finally, the flexibility of the new distribution is illustrated using a real data set.     

A finite mixture approach to joint clustering of individuals and multivariate discrete outcomes

In this work, we modify finite mixtures of factor analysers to provide a method for simultaneous clustering of subjects and multivariate discrete outcomes. The joint clustering is performed through a suitable reparameterization of the outcome (column)-specific parameters. We develop an expectation–maximization-type algorithm for maximum likelihood parameter estimation where the maximization step is divided into orthogonal sub-blocks that refer to row and column-specific parameters, respectively. Model performance is evaluated via a simulation study with varying sample size, number of outcomes and row/column-specific clustering (partitions). We compare the performance of our model with the performance of standard model-based biclustering approaches. The proposed method is also demonstrated on a benchmark data set where a multivariate binary response is considered.     

Inference about regression parameters using highly stratified survey count data with over-dispersion and repeated measurements

We study methods to estimate regression and variance parameters for over-dispersed and correlated count data from highly stratified surveys. Our application involves counts of fish catches from stratified research surveys and we propose a novel model in fisheries science to address changes in survey protocols. A challenge with this model is the large number of nuisance parameters which leads to computational issues and biased statistical inferences. We use a computationally efficient profile generalized estimating equation method and compare it to marginal maximum likelihood (MLE) and restricted MLE (REML) methods. We use REML to address bias and inaccurate confidence intervals because of many nuisance parameters. The marginal MLE and REML approaches involve intractable integrals and we used a new R package that is designed for estimating complex nonlinear models that may include random effects. We conclude from simulation analyses that the REML method provides more reliable statistical inferences among the three methods we investigated.     

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.     

Semiparametric estimation of treatment effect with density ratio model

In this study we propose a unified semiparametric approach to estimate various indices of treatment effect under the density ratio model, which connects two density functions by an exponential tilt. For each index, we construct two estimating functions based on the model and apply the generalized method of moments to improve the estimates. The estimating functions are allowed to be non smooth with respect to parameters and hence make the proposed method more flexible. We establish the asymptotic properties of the proposed estimators and illustrate the application with several simulations and two real data sets.     

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.     

Parameter Orthogonality and Bias Adjustment for Estimating Functions

Abstract.  We consider an extended notion of parameter orthogonality for estimating functions, called nuisance parameter insensitivity, which allows a unified treatment of nuisance parameters for a wide range of methods, including Liang and Zeger's generalized estimating equations. Nuisance parameter insensitivity has several important properties in common with conventional parameter orthogonality, such as the nuisance parameter causing no loss of efficiency for estimating the interest parameter, and a simplified estimation algorithm. We also consider bias adjustment for profile estimating functions, and apply the results to restricted maximum likelihood estimation of dispersion parameters in generalized estimating equations.