Likelihood analysis of joint marginal and conditional models for longitudinal categorical data

The authors develop a Markov model for the analysis of longitudinal categorical data which facilitates modelling both marginal and conditional structures. A likelihood formulation is employed for inference, so the resulting estimators enjoy the optimal properties such as efficiency and consistency, and remain consistent when data are missing at random. Simulation studies demonstrate that the proposed method performs well under a variety of situations. Application to data from a smoking prevention study illustrates the utility of the model and interpretation of covariate effects. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

A modified two-stage approach for joint modelling of longitudinal and time-to-event data

Joint models for longitudinal and time-to-event data have been applied in many different fields of statistics and clinical studies. However, the main difficulty these models have to face with is the computational problem. The requirement for numerical integration becomes severe when the dimension of random effects increases. In this paper, a modified two-stage approach has been proposed to estimate the parameters in joint models. In particular, in the first stage, the linear mixed-effects models and best linear unbiased predictorsare applied to estimate parameters in the longitudinal submodel. In the second stage, an approximation of the fully joint log-likelihood is proposed using the estimated the values of these parameters from the longitudinal submodel. Survival parameters are estimated bymaximizing the approximation of the fully joint log-likelihood. Simulation studies show that the approach performs well, especially when the dimension of random effects increases. Finally, we implement this approach on AIDS data.     

On the multivariate predictive distribution of multi-dimensional effective dose: a Bayesian approach

We propose a Bayesian procedure to sample from the distribution of the multi-dimensional effective dose. This effective dose is the set of dose levels of multiple predictive factors that produce a binary response with a fixed probability.We apply our algorithms to parametric and semiparametric logistics regression models, respectively. The graphical display of random samples obtained through Markov chain Monte Carlo can provide some insight into the predictive distribution.     

Penalized spline joint models for longitudinal and time-to-event data

The joint models for longitudinal data and time-to-event data have recently received numerous attention in clinical and epidemiologic studies. Our interest is in modeling the relationship between event time outcomes and internal time-dependent covariates. In practice, the longitudinal responses often show non linear and fluctuated curves. Therefore, the main aim of this paper is to use penalized splines with a truncated polynomial basis to parameterize the non linear longitudinal process. Then, the linear mixed-effects model is applied to subject-specific curves and to control the smoothing. The association between the dropout process and longitudinal outcomes is modeled through a proportional hazard model. Two types of baseline risk functions are considered, namely a Gompertz distribution and a piecewise constant model. The resulting models are referred to as penalized spline joint models; an extension of the standard joint models. The expectation conditional maximization (ECM) algorithm is applied to estimate the parameters in the proposed models. To validate the proposed algorithm, extensive simulation studies were implemented followed by a case study. In summary, the penalized spline joint models provide a new approach for joint models that have improved the existing standard joint models.     

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 bivariate extension of the beta generated distribution derived from copulas

In this paper, we introduce a new class of bivariate distributions whose marginals are beta-generated distributions. Copulas are employed to construct this bivariate extension of the beta-generated distributions. It is shown that when Archimedean copulas and convex beta generators are used in generating bivariate distributions, the copulas of the resulting distributions also belong to the Archimedean family. The dependence of the proposed bivariate distributions is examined. Simulation results for beta generators and an application to financial risk management are presented.     

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.     

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.     

Joint modeling of multivariate longitudinal mixed measurements and time to event data using a Bayesian approach

In many longitudinal studies multiple characteristics of each individual, along with time to occurrence of an event of interest, are often collected. In such data set, some of the correlated characteristics may be discrete and some of them may be continuous. In this paper, a joint model for analysing multivariate longitudinal data comprising mixed continuous and ordinal responses and a time to event variable is proposed. We model the association structure between longitudinal mixed data and time to event data using a multivariate zero-mean Gaussian process. For modeling discrete ordinal data we assume a continuous latent variable follows the logistic distribution and for continuous data a Gaussian mixed effects model is used. For the event time variable, an accelerated failure time model is considered under different distributional assumptions. For parameter estimation, a Bayesian approach using Markov Chain Monte Carlo is adopted. The performance of the proposed methods is illustrated using some simulation studies. A real data set is also analyzed, where different model structures are used. Model comparison is performed using a variety of statistical criteria.     

Empirical likelihood inference in mixture of semiparametric varying-coefficient models for longitudinal data with non-ignorable dropout

In this paper, empirical likelihood inference in mixture of semiparametric varying-coefficient models for longitudinal data with non-ignorable dropout is investigated. We estimate the non-parametric function based on the estimating equations and the local linear profile-kernel method. An empirical log-likelihood ratio statistic for parametric components is proposed to construct confidence regions and is shown to be an asymptotically chi-squared distribution. The non-parametric version of Wilk's theorem is also derived. A simulation study is undertaken to illustrate the finite sample performance of the proposed method.     

Testing for additivity and joint effects in multivariate nonparametric regression using Fourier and wavelet methods

We consider the problem of testing for additivity and joint effects in multivariate nonparametric regression when the data are modelled as observations of an unknown response function observed on a d-dimensional (d 2) lattice and contaminated with additive Gaussian noise. We propose tests for additivity and joint effects, appropriate for both homogeneous and inhomogeneous response functions, using the particular structure of the data expanded in tensor product Fourier or wavelet bases studied recently by Amato and Antoniadis (2001) and Amato, Antoniadis and De Feis (2002). The corresponding tests are constructed by applying the adaptive Neyman truncation and wavelet thresholding procedures of Fan (1996), for testing a high-dimensional Gaussian mean, to the resulting empirical Fourier and wavelet coefficients. As a consequence, asymptotic normality of the proposed test statistics under the null hypothesis and lower bounds of the corresponding powers under a specific alternative are derived. We use several simulated examples to illustrate the performance of the proposed tests, and we make comparisons with other tests available in the literature.     

Joint modelling of longitudinal response and time-to-event data using conditional distributions: a Bayesian perspective

Over the last 20 or more years a lot of clinical applications and methodological development in the area of joint models of longitudinal and time-to-event outcomes have come up. In these studies, patients are followed until an event, such as death, occurs. In most of the work, using subject-specific random-effects as frailty, the dependency of these two processes has been established. In this article, we propose a new joint model that consists of a linear mixed-effects model for longitudinal data and an accelerated failure time model for the time-to-event data. These two sub-models are linked via a latent random process. This model will capture the dependency of the time-to-event on the longitudinal measurements more directly. Using standard priors, a Bayesian method has been developed for estimation. All computations are implemented using OpenBUGS. Our proposed method is evaluated by a simulation study, which compares the conditional model with a joint model with local independence by way of calibration. Data on Duchenne muscular dystrophy (DMD) syndrome and a set of data in AIDS patients have been analysed.     

Independence distribution preserving joint covariance structures for the multivariate two-group case

We characterize the general nonnegative-definite and positive-definite joint observation covariance structures for the two-group case such that the two sample mean vectors are independent of the two corresponding sample covariance matrices. Also, the sample covariance matrices are distributed as independent noncentral or central Wishart random matrices. We derive and utilize a representation of the general common non-negative-definite solution to a particular system of matrix equations with idempotent coefficient matrices.     

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.     

Estimation in an empirical bayes model for longitudinal and cross‐sectionally clustered binary data

Some studies generate data that can be grouped into clusters in more than one way. Consider for instance a smoking prevention study in which responses on smoking status are collected over several years in a cohort of students from a number of different schools. This yields longitudinal data, also cross‐sectionaliy clustered in schools. The authors present a model for analyzing binary data of this type, combining generalized estimating equations and estimation of random effects to address the longitudinal and cross‐sectional dependence, respectively. The estimation procedure for this model is discussed, as are the results of a simulation study used to investigate the properties of its estimates. An illustration using data from a smoking prevention trial is given.     

Estimation of eigenvalues of the scale matrix of the multivariate f distribution

Let F have the multivariate F distribution with a scale matrix Δ. In this paper, the problem of estimating the eigenvalues of the scale matrix Δ is considered. New class of estimators are obtained which dominate the best linear estimator of the form cF. Simulation study is also carried out to compare the performance of these estimators.     

Longitudinal data analysis in the presence of informative sampling: weighted distribution or joint modelling

ABSTRACT

Weighted distributions, as an example of informative sampling, work appropriately under the missing at random mechanism since they neglect missing values and only completely observed subjects are used in the study plan. However, length-biased distributions, as a special case of weighted distributions, remove the subjects with short length deliberately, which surely meet the missing not at random mechanism. Accordingly, applying length-biased distributions jeopardizes the results by producing biased estimates. Hence, an alternate method has to be used such that the results are improved by means of valid inferences. We propose methods that are based on weighted distributions and joint modelling procedure and compare them in analysing longitudinal data. After introducing three methods in use, a set of simulation studies and analysis of two real longitudinal datasets affirm our claim.     

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.     

Examination and visualisation of the simplifying assumption for vine copulas in three dimensions

Vine copulas are a highly flexible class of dependence models, which are based on the decomposition of the density into bivariate building blocks. For applications one usually makes the simplifying assumption that copulas of conditional distributions are independent of the variables on which they are conditioned. However this assumption has been criticised for being too restrictive. We examine both simplified and non‐simplified vine copulas in three dimensions and investigate conceptual differences. We show and compare contour surfaces of three‐dimensional vine copula models, which prove to be much more informative than the contour lines of the bivariate marginals. Our investigation shows that non‐simplified vine copulas can exhibit arbitrarily irregular shapes, whereas simplified vine copulas appear to be smooth extrapolations of their bivariate margins to three dimensions. In addition to a variety of constructed examples, we also investigate a three‐dimensional subset of the well‐known uranium data set and visually detect the fact that a non‐simplified vine copula is necessary to capture its complex dependence structure.