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.     

Gaussian mixture analysis of covariance

ABSTRACT

In many real-world applications, the traditional theory of analysis of covariance (ANCOVA) leads to inadequate and unreliable results because of violation of the response variable observations from the essential Gaussian assumption that may be due to the heterogeneity of population, the presence of outlier or both of them. In this paper, we develop a Gaussian mixture ANCOVA model for modelling heterogeneous populations with a finite number of subpopulation. We provide the maximum likelihood estimates of the model parameters via an EM algorithm. We also drive the adjusted effects estimators for treatments and covariates. The Fisher information matrix of the model and asymptotic confidence intervals for the parameter are also discussed. We performed a simulation study to assess the performance of the proposed model. A real-world example is also worked out to explained the methodology.     

Joint modeling of hierarchically clustered and overdispersed non‐gaussian continuous outcomes for comet assay data

Multivariate longitudinal or clustered data are commonly encountered in clinical trials and toxicological studies. Typically, there is no single standard endpoint to assess the toxicity or efficacy of the compound of interest, but co‐primary endpoints are available to assess the toxic effects or the working of the compound. Modeling the responses jointly is thus appealing to draw overall inferences using all responses and to capture the association among the responses. Non‐Gaussian outcomes are often modeled univariately using exponential family models. To accommodate both the overdispersion and hierarchical structure in the data, Molenberghs et al. A family of generalized linear models for repeated measures with normal and conjugate random effects. Statistical Science 2010; 25:325–347 proposed using two separate sets of random effects. This papers considers a model for multivariate data with hierarchically clustered and overdispersed non‐Gaussian data. Gamma random effect for the over‐dispersion and normal random effects for the clustering in the data are being used. The two outcomes are jointly analyzed by assuming that the normal random effects for both endpoints are correlated. The association structure between the response is analytically derived. The fit of the joint model to data from a so‐called comet assay are compared with the univariate analysis of the two outcomes. Copyright © 2012 John Wiley & Sons, Ltd.     

Three-step estimation in linear mixed models with skew-t distributions

Linear mixed models based on the normality assumption are widely used in health related studies. Although the normality assumption leads to simple, mathematically tractable, and powerful tests, violation of the assumption may easily invalidate the statistical inference. Transformation of variables is sometimes used to make normality approximately true. In this paper we consider another approach by replacing the normal distributions in linear mixed models by skew-t distributions, which account for skewness and heavy tails for both the random effects and the errors. The full likelihood-based estimator is often difficult to use, but a 3-step estimation procedure is proposed, followed by an application to the analysis of deglutition apnea duration in normal swallows. The example shows that skew-t models often entail more reliable inference than Gaussian models for the skewed data.     

A taxonomy of mixing and outcome distributions based on conjugacy and bridging

Abstract

The generalized linear mixed model (GLMM) is commonly used for the analysis of hierarchical non Gaussian data. It combines an exponential family model formulation with normally distributed random effects. A drawback is the difficulty of deriving convenient marginal mean functions with straightforward parametric interpretations. Several solutions have been proposed, including the marginalized multilevel model (directly formulating the marginal mean, together with a hierarchical association structure) and the bridging approach (choosing the random-effects distribution such that marginal and hierarchical mean functions share functional forms). Another approach, useful in both a Bayesian and a maximum-likelihood setting, is to choose a random-effects distribution that is conjugate to the outcome distribution. In this paper, we contrast the bridging and conjugate approaches. For binary outcomes, using characteristic functions and cumulant generating functions, it is shown that the bridge distribution is unique. Self-bridging is introduced as the situation in which the outcome and random-effects distributions are the same. It is shown that only the Gaussian and degenerate distributions have well-defined cumulant generating functions for which self-bridging holds.     

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.     

Estimating and Testing Nonlinear Local Dependence Between Two Time Series

ABSTRACT

The most common measure of dependence between two time series is the cross-correlation function. This measure gives a complete characterization of dependence for two linear and jointly Gaussian time series, but it often fails for nonlinear and non-Gaussian time series models, such as the ARCH-type models used in finance. The cross-correlation function is a global measure of dependence. In this article, we apply to bivariate time series the nonlinear local measure of dependence called local Gaussian correlation. It generally works well also for nonlinear models, and it can distinguish between positive and negative local dependence. We construct confidence intervals for the local Gaussian correlation and develop a test based on this measure of dependence. Asymptotic properties are derived for the parameter estimates, for the test functional and for a block bootstrap procedure. For both simulated and financial index data, we construct confidence intervals and we compare the proposed test with one based on the ordinary correlation and with one based on the Brownian distance correlation. Financial indexes are examined over a long time period and their local joint behavior, including tail behavior, is analyzed prior to, during and after the financial crisis. Supplementary material for this article is available online.     

Lévy‐based Modelling in Brain Imaging

Abstract. A substantive problem in neuroscience is the lack of valid statistical methods for non‐Gaussian random fields. In the present study, we develop a flexible, yet tractable model for a random field based on kernel smoothing of a so‐called Lévy basis. The resulting field may be Gaussian, but there are many other possibilities, including random fields based on Gamma, inverse Gaussian and normal inverse Gaussian (NIG) Lévy bases. It is easy to estimate the parameters of the model and accordingly to assess by simulation the quantiles of test statistics commonly used in neuroscience. We give a concrete example of magnetic resonance imaging scans that are non‐Gaussian. For these data, simulations under the fitted models show that traditional methods based on Gaussian random field theory may leave small, but significant changes in signal level undetected, while these changes are detectable under a non‐Gaussian Lévy model.     

Local influence of nonlinear mixed effects model based on M-estimation

Abstract

In this work we mainly study the local influence in nonlinear mixed effects model with M-estimation. A robust method to obtain maximum likelihood estimates for parameters is presented, and the local influence of nonlinear mixed models based on robust estimation (M-estimation) by use of the curvature method is systematically discussed. The counting formulas of curvature for case weights perturbation, response variable perturbation and random error covariance perturbation are derived. Simulation studies are carried to access performance of the methods we proposed. We illustrate the diagnostics by an example presented in Davidian and Giltinan, which was analyzed under the non-robust situation.     

Proportional hazards model for discrete data: Some new developments

ABSTRACT

Many times, a product lifetime can be described through a non negative integer valued random variable. In this article, we propose a proportional hazards model for discrete data analogous to the version for continuous data. Some ageing properties of the model are discussed. Stochastic comparison of pair of random variables that follow the model are also made. A new test based on U-statistics is developed for testing that the proportionality parameter in the proposed model is 1. The asymptotic properties of the proposed test are studied. We present some numerical results to asses the performance of the test procedure.     

Augmented mixed beta regression models with skew-normal independent distributions: Bayesian analysis of labor force data

Abstract

Augmented mixed beta regression models are suitable choices for modeling continuous response variables on the closed interval [0, 1]. The random eeceeects in these models are typically assumed to be normally distributed, but this assumption is frequently violated in some applied studies. In this paper, an augmented mixed beta regression model with skew-normal independent distribution for random effects are used. Next, we adopt a Bayesian approach for parameter estimation using the MCMC algorithm. The methods are then evaluated using some intensive simulation studies. Finally, the proposed models have applied to analyze a dataset from an Iranian Labor Force Survey.     

Multiscale Gaussian convolution algorithm for estimate of Gaussian mixture model

Abstract

This paper introduces a multiscale Gaussian convolution model of Gaussian mixture (MGC-GMM) via the convolution of the GMM and a multiscale Gaussian window function. It is found that the MGC-GMM is still a Gaussian mixture model, and its parameters can be mapped back to the parameters of the GMM. Meanwhile, the multiscale probability density function (MPDF) of the MGC-GMM can be viewed as the mathematical expectation of a random process induced by the Gaussian window function and the GMM, which can be directly estimated by the use of sample data. Based on the estimated MPDF, a novel algorithm denoted by the MGC is proposed for the selection of model and the parameter estimates of the GMM, where the component number and the means of the GMM are respectively determined by the number and the locations of the maximum points of the MPDF, and the numerical algorithms for the weight and variance parameters of the GMM are derived. The MGC is suitable for the GMM with diagonal covariance matrices. A MGC-EM algorithm is also presented for the generalized GMM, where the GMM is estimated using the EM algorithm by taking the estimates from the MGC as initial parameters of the GMM model. The proposed algorithms are tested via a series of simulated sample sets from the given GMM models, and the results show that the proposed algorithms can effectively estimate the GMM model.     

A bayesian analysis of autoregressive models with random normal coefficients

In this paper we consider a Bayesian analysis for an autoregressive model with random normal coefficients (RCA). For the proposed procedure we use conjugate priors for some parameters and improper vague priors for others. The inference for the parameters is made via Gibbs sampler and the convergence is assessed with multiple chains and Gelman and Rubin criterium. Forecasts are based on the predictive density of future observations. Some remarks are also made regarding order determination and stationarity. Applications to simulated and real series are given.     

A permutation-based Bayesian approach for inverse covariance estimation

Abstract

Covariance estimation and selection for multivariate datasets in a high-dimensional regime is a fundamental problem in modern statistics. Gaussian graphical models are a popular class of models used for this purpose. Current Bayesian methods for inverse covariance matrix estimation under Gaussian graphical models require the underlying graph and hence the ordering of variables to be known. However, in practice, such information on the true underlying model is often unavailable. We therefore propose a novel permutation-based Bayesian approach to tackle the unknown variable ordering issue. In particular, we utilize multiple maximum a posteriori estimates under the DAG-Wishart prior for each permutation, and subsequently construct the final estimate of the inverse covariance matrix. The proposed estimator has smaller variability and yields order-invariant property. We establish posterior convergence rates under mild assumptions and illustrate that our method outperforms existing approaches in estimating the inverse covariance matrices via simulation studies.     

A Bayesian random effects model for analyzing mixed negative binomial and continuous longitudinal responses

ABSTRACT

A general Bayesian random effects model for analyzing longitudinal mixed correlated continuous and negative binomial responses with and without missing data is presented. This Bayesian model, given some random effects, uses a normal distribution for the continuous response and a negative binomial distribution for the count response. A Markov Chain Monte Carlo sampling algorithm is described for estimating the posterior distribution of the parameters. This Bayesian model is illustrated by a simulation study. For sensitivity analysis to investigate the change of parameter estimates with respect to the perturbation from missing at random to not missing at random assumption, the use of posterior curvature is proposed. The model is applied to a medical data, obtained from an observational study on women, where the correlated responses are the negative binomial response of joint damage and continuous response of body mass index. The simultaneous effects of some covariates on both responses are also investigated.     

THE LOG-EIG DISTRIBUTION: A NEW PROBABILITY MODEL FOR LIFETIME DATA

ABSTRACT

In this paper, we propose a new probability model called the log-EIG distribution for lifetime data analysis. Some important properties of the proposed model and maximum likelihood estimation of its parameters are discussed. Its relationship with the exponential inverse Gaussian distribution is similar to that of the lognormal and the normal distributions. Through applications to well-known datasets, we show that the log-EIG distribution competes well, and in some instances even provides a better fit than the commonly used lifetime models such as the gamma, lognormal, Weibull and inverse Gaussian distributions. It can accommodate situations where an increasing failure rate model is required as well as those with a decreasing failure rate at larger times.     

A Sequential Multi-Hypothesis Test for the Mean Function of a Discrete-Time Gaussian Process

Abstract

A sequential multi-hypothesis test for the mean function of a discrete-time Gaussian process with known covariance kernel is developed. It is obtained by applying the Bechhofer-Kiefer-Sobel generalized sequential probability ratio test GSPRT, and its properties are studied analytically. Selected applications to i.i.d. normal random variables, observation in a time series AR(1) model, and Wiener processes are given.     

Specifying a Gaussian Markov Random Field by a Sparse Cholesky Triangle

ABSTRACT

This note discusses the approach of specifying a Gaussian Markov random field (GMRF) by the Cholesky triangle of the precision matrix. A such representation can be made extremely sparse using numerical techniques for incomplete sparse Cholesky factorization, and provide very computational efficient representation for simulating from the GMRF. However, we provide theoretical and empirical justification showing that the sparse Cholesky triangle representation is fragile when conditioning a GMRF on a subset of the variables or observed data, meaning that the computational cost increases.     

Randomized heuristic algorithms for orthogonal projection of a point onto a set

Abstract

The problem of orthogonal projection of a point onto a set is an essential problem of computational geometry. This problem has many practical applications in different areas such as robotics, computer graphics and so on. In the present paper three algorithms for solving this problem are proposed. This algorithms are based on the idea of heuristic random search. Numerical experiments illustrating the work of the proposed methods are presented.     

A graphical model selection tool for mixed models

ABSTRACT

Model selection can be defined as the task of estimating the performance of different models in order to choose the most parsimonious one, among a potentially very large set of candidate statistical models. We propose a graphical representation to be considered as an extension to the class of mixed models of the deviance plot proposed in the literature within the framework of classical and generalized linear models. This graphical representation allows, once a reduced number of models have been selected, to identify important covariates focusing only on the fixed effects component, assuming the random part properly specified. Nevertheless, we suggest also a standalone figure representing the residual random variance ratio: a cross-evaluation of the two graphical representations will allow to derive some conclusions on the random part specification of the model and a more accurate selection of the final model.