Joint modeling of bottle use,daily milk intake from bottles,and daily energy intake in toddlers

The current study follows an educational intervention on bottle-weaning to simultaneously evaluate effects of the bottle-weaning intervention on reducing bottle use, daily milk intake from bottles, and daily energy intake in toddlers aged 11–13 months. In this paper, we propose to use shared parameter models and random effects models to model these outcomes jointly. Our joint models consist of two submodels: a two-part submodel for modeling the odds of bottle use and the intensity of daily milk intake from bottles, and a linear mixed submodel for modeling the intensity of daily energy intake. The two submodels are linked by either shared random effects or separate but correlated random effects. We investigate whether the intervention effects, parameter estimates, and model fit differ between shared parameter models and random effects models.     

A linear mixed model for analyzing longitudinal skew-normal responses with random dropout

In this paper, a linear mixed effects model is used to fit skewed longitudinal data in the presence of dropout. Two distributional assumptions are considered to produce background for heavy tailed models. One is the linear mixed model with skew-normal random effects and normal errors and the other one is the linear mixed model with skew-normal errors and normal random effects. An ECM algorithm is developed to obtain the parameter estimates. Also an empirical Bayes approach is used for estimating random effects. A simulation study is implemented to investigate the performance of the presented algorithm. Results of an application are also reported where standard errors of estimates are calculated using the Bootstrap approach.     

Modelling growth and decline in lung function in Duchenne's muscular dystrophy with an augmented linear mixed effects model

Summary.  Longitudinal modelling of lung function in Duchenne's muscular dystrophy is complicated by a mixture of both growth and decline in lung function within each subject, an unknown point of separation between these phases and significant heterogeneity between individual trajectories. Linear mixed effects models can be used, assuming a single changepoint for all cases; however, this assumption may be incorrect. The paper describes an extension of linear mixed effects modelling in which random changepoints are integrated into the model as parameters and estimated by using a stochastic EM algorithm. We find that use of this 'mixture modelling' approach improves the fit significantly.     

Identifiable finite mixtures of location models for clustering mixed-mode data

For clustering mixed categorical and continuous data, Lawrence and Krzanowski (1996) proposed a finite mixture model in which component densities conform to the location model. In the graphical models literature the location model is known as the homogeneous Conditional Gaussian model. In this paper it is shown that their model is not identifiable without imposing additional restrictions. Specifically, for g groups and m locations, (g!)m–1 distinct sets of parameter values (not including permutations of the group mixing parameters) produce the same likelihood function. Excessive shrinkage of parameter estimates in a simulation experiment reported by Lawrence and Krzanowski (1996) is shown to be an artifact of the model's non-identifiability. Identifiable finite mixture models can be obtained by imposing restrictions on the conditional means of the continuous variables. These new identified models are assessed in simulation experiments. The conditional mean structure of the continuous variables in the restricted location mixture models is similar to that in the underlying variable mixture models proposed by Everitt (1988), but the restricted location mixture models are more computationally tractable.     

Mixed effects smoothing spline analysis of variance

We propose a general family of nonparametric mixed effects models. Smoothing splines are used to model the fixed effects and are estimated by maximizing the penalized likelihood function. The random effects are generic and are modelled parametrically by assuming that the covariance function depends on a parsimonious set of parameters. These parameters and the smoothing parameter are estimated simultaneously by the generalized maximum likelihood method. We derive a connection between a nonparametric mixed effects model and a linear mixed effects model. This connection suggests a way of fitting a nonparametric mixed effects model by using existing programs. The classical two-way mixed models and growth curve models are used as examples to demonstrate how to use smoothing spline analysis-of-variance decompositions to build nonparametric mixed effects models. Similarly to the classical analysis of variance, components of these nonparametric mixed effects models can be interpreted as main effects and interactions. The penalized likelihood estimates of the fixed effects in a two-way mixed model are extensions of James–Stein shrinkage estimates to correlated observations. In an example three nested nonparametric mixed effects models are fitted to a longitudinal data set.     

Estimating the variance for heterogeneity in arm‐based network meta‐analysis

Network meta‐analysis can be implemented by using arm‐based or contrast‐based models. Here we focus on arm‐based models and fit them using generalized linear mixed model procedures. Full maximum likelihood (ML) estimation leads to biased trial‐by‐treatment interaction variance estimates for heterogeneity. Thus, our objective is to investigate alternative approaches to variance estimation that reduce bias compared with full ML. Specifically, we use penalized quasi‐likelihood/pseudo‐likelihood and hierarchical (h) likelihood approaches. In addition, we consider a novel model modification that yields estimators akin to the residual maximum likelihood estimator for linear mixed models. The proposed methods are compared by simulation, and 2 real datasets are used for illustration. Simulations show that penalized quasi‐likelihood/pseudo‐likelihood and h‐likelihood reduce bias and yield satisfactory coverage rates. Sum‐to‐zero restriction and baseline contrasts for random trial‐by‐treatment interaction effects, as well as a residual ML‐like adjustment, also reduce bias compared with an unconstrained model when ML is used, but coverage rates are not quite as good. Penalized quasi‐likelihood/pseudo‐likelihood and h‐likelihood are therefore recommended.     

索赔次数的开放式混合泊松分布研究

本文建立了索赔次数的多风险类别混合泊松模型。首先,考虑索赔次数的零膨胀、厚尾性和异质性等特征,建立风险类别待定的开放式混合泊松模型,开放式结构使该模型对实际数据的多样特征和风险类别具有良好的自适应性;其次,定义混合权重参数的iSCAD惩罚函数,实现对权重参数的筛选;最后,借助EM算法求得模型参数,实现对各风险类别下索赔次数的估计。借助iSCAD惩罚函数,给出最优混合数,避免传统混合模型中主观选择的弊端,克服传统混合模型中结构复杂、参数估计没有显式表达式、估计结果不便于解释等问题。基于三组风险特征多样数据的实证分析,本文发现该模型可以显著改进现有模型的拟合效果。     

A joint marginalized multilevel model for longitudinal outcomes

The shared-parameter model and its so-called hierarchical or random-effects extension are widely used joint modeling approaches for a combination of longitudinal continuous, binary, count, missing, and survival outcomes that naturally occurs in many clinical and other studies. A random effect is introduced and shared or allowed to differ between two or more repeated measures or longitudinal outcomes, thereby acting as a vehicle to capture association between the outcomes in these joint models. It is generally known that parameter estimates in a linear mixed model (LMM) for continuous repeated measures or longitudinal outcomes allow for a marginal interpretation, even though a hierarchical formulation is employed. This is not the case for the generalized linear mixed model (GLMM), that is, for non-Gaussian outcomes. The aforementioned joint models formulated for continuous and binary or two longitudinal binomial outcomes, using the LMM and GLMM, will naturally have marginal interpretation for parameters associated with the continuous outcome but a subject-specific interpretation for the fixed effects parameters relating covariates to binary outcomes. To derive marginally meaningful parameters for the binary models in a joint model, we adopt the marginal multilevel model (MMM) due to Heagerty [13] and Heagerty and Zeger [14] and formulate a joint MMM for two longitudinal responses. This enables to (1) capture association between the two responses and (2) obtain parameter estimates that have a population-averaged interpretation for both outcomes. The model is applied to two sets of data. The results are compared with those obtained from the existing approaches such as generalized estimating equations, GLMM, and the model of Heagerty [13]. Estimates were found to be very close to those from single analysis per outcome but the joint model yields higher precision and allows for quantifying the association between outcomes. Parameters were estimated using maximum likelihood. The model is easy to fit using available tools such as the SAS NLMIXED procedure.     

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.     

The Sichel model and the mixing and truncation order

The analysis of word frequency count data can be very useful in authorship attribution problems. Zero-truncated generalized inverse Gaussian–Poisson mixture models are very helpful in the analysis of these kinds of data because their model-mixing density estimates can be used as estimates of the density of the word frequencies of the vocabulary. It is found that this model provides excellent fits for the word frequency counts of very long texts, where the truncated inverse Gaussian–Poisson special case fails because it does not allow for the large degree of over-dispersion in the data. The role played by the three parameters of this truncated GIG-Poisson model is also explored. Our second goal is to compare the fit of the truncated GIG-Poisson mixture model with the fit of the model that results from switching the order of the mixing and truncation stages. A heuristic interpretation of the mixing distribution estimates obtained under this alternative GIG-truncated Poisson mixture model is also provided.     

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.     

Using regression mixture models with non-normal data: examining an ordered polytomous approach

Mild to moderate skew in errors can substantially impact regression mixture model results; one approach for overcoming this includes transforming the outcome into an ordered categorical variable and using a polytomous regression mixture model. This is effective for retaining differential effects in the population; however, bias in parameter estimates and model fit warrant further examination of this approach at higher levels of skew. The current study used Monte Carlo simulations; 3000 observations were drawn from each of two subpopulations differing in the effect of X on Y. Five hundred simulations were performed in each of the 10 scenarios varying in levels of skew in one or both classes. Model comparison criteria supported the accurate two-class model, preserving the differential effects, while parameter estimates were notably biased. The appropriate number of effects can be captured with this approach but we suggest caution when interpreting the magnitude of the effects.     

Review and implementation of cure models based on first hitting times for Wiener processes

The development of models and methods for cure rate estimation has recently burgeoned into an important subfield of survival analysis. Much of the literature focuses on the standard mixture model. Recently, process-based models have been suggested. We focus on several models based on first passage times for Wiener processes. Whitmore and others have studied these models in a variety of contexts. Lee and Whitmore (Stat Sci 21(4):501–513, 2006) give a comprehensive review of a variety of first hitting time models and briefly discuss their potential as cure rate models. In this paper, we study the Wiener process with negative drift as a possible cure rate model but the resulting defective inverse Gaussian model is found to provide a poor fit in some cases. Several possible modifications are then suggested, which improve the defective inverse Gaussian. These modifications include: the inverse Gaussian cure rate mixture model; a mixture of two inverse Gaussian models; incorporation of heterogeneity in the drift parameter; and the addition of a second absorbing barrier to the Wiener process, representing an immunity threshold. This class of process-based models is a useful alternative to the standard model and provides an improved fit compared to the standard model when applied to many of the datasets that we have studied. Implementation of this class of models is facilitated using expectation-maximization (EM) algorithms and variants thereof, including the gradient EM algorithm. Parameter estimates for each of these EM algorithms are given and the proposed models are applied to both real and simulated data, where they perform well.     

Robust multivariate mixture regression models with incomplete data

Multivariate mixture regression models can be used to investigate the relationships between two or more response variables and a set of predictor variables by taking into consideration unobserved population heterogeneity. It is common to take multivariate normal distributions as mixing components, but this mixing model is sensitive to heavy-tailed errors and outliers. Although normal mixture models can approximate any distribution in principle, the number of components needed to account for heavy-tailed distributions can be very large. Mixture regression models based on the multivariate t distributions can be considered as a robust alternative approach. Missing data are inevitable in many situations and parameter estimates could be biased if the missing values are not handled properly. In this paper, we propose a multivariate t mixture regression model with missing information to model heterogeneity in regression function in the presence of outliers and missing values. Along with the robust parameter estimation, our proposed method can be used for (i) visualization of the partial correlation between response variables across latent classes and heterogeneous regressions, and (ii) outlier detection and robust clustering even under the presence of missing values. We also propose a multivariate t mixture regression model using MM-estimation with missing information that is robust to high-leverage outliers. The proposed methodologies are illustrated through simulation studies and real data analysis.     

Estimation of regression vectors in linear mixed models with Dirichlet process random effects

The Dirichlet process has been used extensively in Bayesian non parametric modeling, and has proven to be very useful. In particular, mixed models with Dirichlet process random effects have been used in modeling many types of data and can often outperform their normal random effect counterparts. Here we examine the linear mixed model with Dirichlet process random effects from a classical view, and derive the best linear unbiased estimator (BLUE) of the fixed effects. We are also able to calculate the resulting covariance matrix and find that the covariance is directly related to the precision parameter of the Dirichlet process, giving a new interpretation of this parameter. We also characterize the relationship between the BLUE and the ordinary least-squares (OLS) estimator and show how confidence intervals can be approximated.     

A note on model selection using information criteria for general linear models estimated using REML

It is common practice to compare the fit of non‐nested models using the Akaike (AIC) or Bayesian (BIC) information criteria. The basis of these criteria is the log‐likelihood evaluated at the maximum likelihood estimates of the unknown parameters. For the general linear model (and the linear mixed model, which is a special case), estimation is usually carried out using residual or restricted maximum likelihood (REML). However, for models with different fixed effects, the residual likelihoods are not comparable and hence information criteria based on the residual likelihood cannot be used. For model selection, it is often suggested that the models are refitted using maximum likelihood to enable the criteria to be used. The first aim of this paper is to highlight that both the AIC and BIC can be used for the general linear model by using the full log‐likelihood evaluated at the REML estimates. The second aim is to provide a derivation of the criteria under REML estimation. This aim is achieved by noting that the full likelihood can be decomposed into a marginal (residual) and conditional likelihood and this decomposition then incorporates aspects of both the fixed effects and variance parameters. Using this decomposition, the appropriate information criteria for model selection of models which differ in their fixed effects specification can be derived. An example is presented to illustrate the results and code is available for analyses using the ASReml‐R package.     

INFERENCE IN DIRICHLET PROCESS MIXED GENERALIZED LINEAR MODELS BY USING MONTE CARLO EM

Generalized linear mixed models are widely used for describing overdispersed and correlated data. Such data arise frequently in studies involving clustered and hierarchical designs. A more flexible class of models has been developed here through the Dirichlet process mixture. An additional advantage of using such mixture models is that the observations can be grouped together on the basis of the overdispersion present in the data. This paper proposes a partial empirical Bayes method for estimating all the model parameters by adopting a version of the EM algorithm. An augmented model that helps to implement an efficient Gibbs sampling scheme, under the non‐conjugate Dirichlet process generalized linear model, generates observations from the conditional predictive distribution of unobserved random effects and provides an estimate of the average number of mixing components in the Dirichlet process mixture. A simulation study has been carried out to demonstrate the consistency of the proposed method. The approach is also applied to a study on outdoor bacteria concentration in the air and to data from 14 retrospective lung‐cancer studies.     

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.     

Why a time effect often has a limited impact on capture‐recapture estimates in closed populations

The author is concerned with log‐linear estimators of the size N of a population in a capture‐recapture experiment featuring heterogeneity in the individual capture probabilities and a time effect. He also considers models where the first capture influences the probability of subsequent captures. He derives several results from a new inequality associated with a dispersive ordering for discrete random variables. He shows that in a log‐linear model with inter‐individual heterogeneity, the estimator N is an increasing function of the heterogeneity parameter. He also shows that the inclusion of a time effect in the capture probabilities decreases N in models without heterogeneity. He further argues that a model featuring heterogeneity can accommodate a time effect through a small change in the heterogeneity parameter. He demonstrates these results using an inequality for the estimators of the heterogeneity parameters and illustrates them in a Monte Carlo experiment     

Keep it simple: estimation strategies for ordered response models with fixed effects

By running Monte Carlo simulations, we compare different estimation strategies of ordered response models in the presence of non-random unobserved heterogeneity. We find that very simple binary recoding schemes deliver parameter estimates with very low bias and high efficiency. Furthermore, if the researcher is interested in the relative size of parameters the simple linear fixed effects model is the method of choice.