Finite mixture models with concomitant information: assessing diagnostic criteria for diabetes

The World Health Organization (WHO) diagnostic criteria for diabetes mellitus were determined in part by evidence that in some populations the plasma glucose level 2 h after an oral glucose load is a mixture of two distinct distributions. We present a finite mixture model that allows the two component densities to be generalized linear models and the mixture probability to be a logistic regression model. The model allows us to estimate the prevalence of diabetes and sensitivity and specificity of the diagnostic criteria as a function of covariates and to estimate them in the absence of an external standard. Sensitivity is the probability that a test indicates disease conditionally on disease being present. Specificity is the probability that a test indicates no disease conditionally on no disease being present. We obtained maximum likelihood estimates via the EM algorithm and derived the standard errors from the information matrix and by the bootstrap. In the application to data from the diabetes in Egypt project a two-component mixture model fits well and the two components are interpreted as normal and diabetes. The means and variances are similar to results found in other populations. The minimum misclassification cutpoints decrease with age, are lower in urban areas and are higher in rural areas than the 200 mg dl^-1 cutpoint recommended by the WHO. These differences are modest and our results generally support the WHO criterion. Our methods allow the direct inclusion of concomitant data whereas past analyses were based on partitioning the data.     

A Bayesian approach of joint models for clustered zero-inflated count data with skewness and measurement errors

Count data with excess zeros are widely encountered in the fields of biomedical, medical, public health and social survey, etc. Zero-inflated Poisson (ZIP) regression models with mixed effects are useful tools for analyzing such data, in which covariates are usually incorporated in the model to explain inter-subject variation and normal distribution is assumed for both random effects and random errors. However, in many practical applications, such assumptions may be violated as the data often exhibit skewness and some covariates may be measured with measurement errors. In this paper, we deal with these issues simultaneously by developing a Bayesian joint hierarchical modeling approach. Specifically, by treating intercepts and slopes in logistic and Poisson regression as random, a flexible two-level ZIP regression model is proposed, where a covariate process with measurement errors is established and a skew-t-distribution is considered for both random errors and random effects. Under the Bayesian framework, model selection is carried out using deviance information criterion (DIC) and a goodness-of-fit statistics is also developed for assessing the plausibility of the posited model. The main advantage of our method is that it allows for more robustness and correctness for investigating heterogeneity from different levels, while accommodating the skewness and measurement errors simultaneously. An application to Shanghai Youth Fitness Survey is used as an illustrate example. Through this real example, it is showed that our approach is of interest and usefulness for applications.     

A dependent Dirichlet process model for survival data with competing risks

In this paper, we first propose a dependent Dirichlet process (DDP) model using a mixture of Weibull models with each mixture component resembling a Cox model for survival data. We then build a Dirichlet process mixture model for competing risks data without regression covariates. Next we extend this model to a DDP model for competing risks regression data by using a multiplicative covariate effect on subdistribution hazards in the mixture components. Though built on proportional hazards (or subdistribution hazards) models, the proposed nonparametric Bayesian regression models do not require the assumption of constant hazard (or subdistribution hazard) ratio. An external time-dependent covariate is also considered in the survival model. After describing the model, we discuss how both cause-specific and subdistribution hazard ratios can be estimated from the same nonparametric Bayesian model for competing risks regression. For use with the regression models proposed, we introduce an omnibus prior that is suitable when little external information is available about covariate effects. Finally we compare the models’ performance with existing methods through simulations. We also illustrate the proposed competing risks regression model with data from a breast cancer study. An R package “DPWeibull” implementing all of the proposed methods is available at CRAN.

     

Bayesian adjustment for unidirectional misclassification in ordinal covariates

In this paper, we study the identification of Bayesian regression models, when an ordinal covariate is subject to unidirectional misclassification. Xia and Gustafson [Bayesian regression models adjusting for unidirectional covariate misclassification. Can J Stat. 2016;44(2):198–218] obtained model identifiability for non-binary regression models, when there is a binary covariate subject to unidirectional misclassification. In the current paper, we establish the moment identifiability of regression models for misclassified ordinal covariates with more than two categories, based on forms of observable moments. Computational studies are conducted that confirm the theoretical results. We apply the method to two datasets, one from the Medical Expenditure Panel Survey (MEPS), and the other from Translational Research Investigating Underlying Disparities in Acute Myocardial infarction Patients Health Status (TRIUMPH).     

Density regression using repulsive distributions

Flexible regression is a traditional motivation for the development of non-parametric Bayesian models. A popular approach for this involves a joint model for responses and covariates, from which the desired result arises by conditioning on the covariates. Many such models involve the convolution of a continuous kernel with some discrete random probability measure defined as an infinite mixture of i.i.d. atoms. Following this strategy, we propose a flexible model that involves the concept of repulsion between atoms. We show that this results in a more parsimonious representation of the regression than the i.i.d. counterpart. The key aspect is that repulsion discourages mixture components that are near each other, thus favouring parsimony. We show that the conditional model retains the repulsive features, thus facilitating interpretation of the resulting flexible regression, and with little or no sacrifice of model fit compared to the infinite mixture case. We show the utility of the methodology by way of a small simulation study and an application to a well-known data set.     

Multiple imputation of a randomly censored covariate improves logistic regression analysis

Randomly censored covariates arise frequently in epidemiologic studies. The most commonly used methods, including complete case and single imputation or substitution, suffer from inefficiency and bias. They make strong parametric assumptions or they consider limit of detection censoring only. We employ multiple imputation, in conjunction with semi-parametric modeling of the censored covariate, to overcome these shortcomings and to facilitate robust estimation. We develop a multiple imputation approach for randomly censored covariates within the framework of a logistic regression model. We use the non-parametric estimate of the covariate distribution or the semi-parametric Cox model estimate in the presence of additional covariates in the model. We evaluate this procedure in simulations, and compare its operating characteristics to those from the complete case analysis and a survival regression approach. We apply the procedures to an Alzheimer's study of the association between amyloid positivity and maternal age of onset of dementia. Multiple imputation achieves lower standard errors and higher power than the complete case approach under heavy and moderate censoring and is comparable under light censoring. The survival regression approach achieves the highest power among all procedures, but does not produce interpretable estimates of association. Multiple imputation offers a favorable alternative to complete case analysis and ad hoc substitution methods in the presence of randomly censored covariates within the framework of logistic regression.     

Curve prediction and clustering with mixtures of Gaussian process functional regression models

Shi, Wang, Murray-Smith and Titterington (Biometrics 63:714–723, 2007) proposed a Gaussian process functional regression (GPFR) model to model functional response curves with a set of functional covariates. Two main problems are addressed by their method: modelling nonlinear and nonparametric regression relationship and modelling covariance structure and mean structure simultaneously. The method gives very good results for curve fitting and prediction but side-steps the problem of heterogeneity. In this paper we present a new method for modelling functional data with ‘spatially’ indexed data, i.e., the heterogeneity is dependent on factors such as region and individual patient’s information. For data collected from different sources, we assume that the data corresponding to each curve (or batch) follows a Gaussian process functional regression model as a lower-level model, and introduce an allocation model for the latent indicator variables as a higher-level model. This higher-level model is dependent on the information related to each batch. This method takes advantage of both GPFR and mixture models and therefore improves the accuracy of predictions. The mixture model has also been used for curve clustering, but focusing on the problem of clustering functional relationships between response curve and covariates, i.e. the clustering is based on the surface shape of the functional response against the set of functional covariates. The model is examined on simulated data and real data.     

Performance of Wald-type estimator for parametric component in partial linear regression with a mixture of Berkson and classical error models

This article discusses a consistent and almost unbiased estimation approach in partial linear regression for parameters of interest when the regressors are contaminated with a mixture of Berkson and classical errors. Advantages of the presented procedure are: (1) random errors and observations are not necessarily to be parametric settings; (2) there is no need to use additional sample information, and to consider the estimation of nuisance parameters. We will examine the performance of our presented estimate in a variety of numerical examples through Monte Carlo simulation. The proposed approach is also illustrated in the analysis of an air pollution data.     

Bayesian estimation of logistic regression with misclassified covariates and response

Measurement error is a commonly addressed problem in psychometrics and the behavioral sciences, particularly where gold standard data either does not exist or are too expensive. The Bayesian approach can be utilized to adjust for the bias that results from measurement error in tests. Bayesian methods offer other practical advantages for the analysis of epidemiological data including the possibility of incorporating relevant prior scientific information and the ability to make inferences that do not rely on large sample assumptions. In this paper we consider a logistic regression model where both the response and a binary covariate are subject to misclassification. We assume both a continuous measure and a binary diagnostic test are available for the response variable but no gold standard test is assumed available. We consider a fully Bayesian analysis that affords such adjustments, accounting for the sources of error and correcting estimates of the regression parameters. Based on the results from our example and simulations, the models that account for misclassification produce more statistically significant results, than the models that ignore misclassification. A real data example on math disorders is considered.     

Inferences in dynamic logit models in semi-parametric setup for repeated binary data

Binary dynamic fixed and mixed logit models are extensively studied in the literature. These models are developed to examine the effects of certain fixed covariates through a parametric regression function as a part of the models. However, there are situations where one may like to consider more covariates in the model but their direct effect is not of interest. In this paper we propose a generalization of the existing binary dynamic logit (BDL) models to the semi-parametric longitudinal setup to address this issue of additional covariates. The regression function involved in such a semi-parametric BDL model contains (i) a parametric linear regression function in some primary covariates, and (ii) a non-parametric function in certain secondary covariates. We use a simple semi-parametric conditional quasi-likelihood approach for consistent estimation of the non-parametric function, and a semi-parametric likelihood approach for the joint estimation of the main regression and dynamic dependence parameters of the model. The finite sample performance of the estimation approaches is examined through a simulation study. The asymptotic properties of the estimators are also discussed. The proposed model and the estimation approaches are illustrated by reanalysing a longitudinal infectious disease data.     

R package for analysis of data with mixed measurement error and misclassification in covariates: augSIMEX

Measurement error and misclassification arise commonly in various data collection processes. It is well-known that ignoring these features in the data analysis usually leads to biased inference. With the generalized linear model setting, Yi et al. [Functional and structural methods with mixed measurement error and misclassification in covariates. J Am Stat Assoc. 2015;110:681–696] developed inference methods to adjust for the effects of measurement error in continuous covariates and misclassification in discrete covariates simultaneously for the scenario where validation data are available. The augmented simulation-extrapolation (SIMEX) approach they developed generalizes the usual SIMEX method which is only applicable to handle continuous error-prone covariates. To implement this method, we develop an R package, augSIMEX, for public use. Simulation studies are conducted to illustrate the use of the algorithm. This package is available at CRAN.     

Dimensionally reduced mixtures of regression models

A mixture of regression models for multivariate observed variables which contextually involves a dimension reduction step through a linear factor model is proposed. The model estimation is performed via the EM-algorithm and a procedure to compute asymptotic standard errors for the parameter estimates is developed. The proposed approach is applied to the study of students satisfaction towards different aspects of their school as a function of various covariates.     

Model selection in finite mixture of regression models: a Bayesian approach with innovative weighted g priors and reversible jump Markov chain Monte Carlo implementation

Finite mixture of regression (FMR) models are aimed at characterizing subpopulation heterogeneity stemming from different sets of covariates that impact different groups in a population. We address the contemporary problem of simultaneously conducting covariate selection and determining the number of mixture components from a Bayesian perspective that can incorporate prior information. We propose a Gibbs sampling algorithm with reversible jump Markov chain Monte Carlo implementation to accomplish concurrent covariate selection and mixture component determination in FMR models. Our Bayesian approach contains innovative features compared to previously developed reversible jump algorithms. In addition, we introduce component-adaptive weighted g priors for regression coefficients, and illustrate their improved performance in covariate selection. Numerical studies show that the Gibbs sampler with reversible jump implementation performs well, and that the proposed weighted priors can be superior to non-adaptive unweighted priors.     

A mixture of experts latent position cluster model for social network data

Social network data represent the interactions between a group of social actors. Interactions between colleagues and friendship networks are typical examples of such data.The latent space model for social network data locates each actor in a network in a latent (social) space and models the probability of an interaction between two actors as a function of their locations. The latent position cluster model extends the latent space model to deal with network data in which clusters of actors exist — actor locations are drawn from a finite mixture model, each component of which represents a cluster of actors.A mixture of experts model builds on the structure of a mixture model by taking account of both observations and associated covariates when modeling a heterogeneous population. Herein, a mixture of experts extension of the latent position cluster model is developed. The mixture of experts framework allows covariates to enter the latent position cluster model in a number of ways, yielding different model interpretations.Estimates of the model parameters are derived in a Bayesian framework using a Markov Chain Monte Carlo algorithm. The algorithm is generally computationally expensive — surrogate proposal distributions which shadow the target distributions are derived, reducing the computational burden.The methodology is demonstrated through an illustrative example detailing relationships between a group of lawyers in the USA.     

Systematically misclassified binary dependent variables

ABSTRACT

When a binary dependent variable is misclassified, that is, recorded in the category other than where it really belongs, probit and logit estimates are biased and inconsistent. In some cases, the probability of misclassification may vary systematically with covariates, and thus be endogenous. In this paper, we develop an estimation approach that corrects for endogenous misclassification, validate our approach using a simulation study, and apply it to the analysis of a treatment program designed to improve family dynamics. Our results show that endogenous misclassification could lead to potentially incorrect conclusions unless corrected using an appropriate technique.     

Nonparametric covariate adjustment for receiver operating characteristic curves

The accuracy of a diagnostic test is typically characterized using the receiver operating characteristic (ROC) curve. Summarizing indexes such as the area under the ROC curve (AUC) are used to compare different tests as well as to measure the difference between two populations. Often additional information is available on some of the covariates which are known to influence the accuracy of such measures. The authors propose nonparametric methods for covariate adjustment of the AUC. Models with normal errors and possibly non‐normal errors are discussed and analyzed separately. Nonparametric regression is used for estimating mean and variance functions in both scenarios. In the model that relaxes the assumption of normality, the authors propose a covariate‐adjusted Mann–Whitney estimator for AUC estimation which effectively uses available data to construct working samples at any covariate value of interest and is computationally efficient for implementation. This provides a generalization of the Mann–Whitney approach for comparing two populations by taking covariate effects into account. The authors derive asymptotic properties for the AUC estimators in both settings, including asymptotic normality, optimal strong uniform convergence rates and mean squared error (MSE) consistency. The MSE of the AUC estimators was also assessed in smaller samples by simulation. Data from an agricultural study were used to illustrate the methods of analysis. The Canadian Journal of Statistics 38:27–46; 2010 © 2009 Statistical Society of Canada     

A Bayesian Adjustment for Covariate Misclassification with Correlated Binary Outcome Data

Estimated associations between an outcome variable and misclassified covariates tend to be biased when the methods of estimation that ignore the classification error are applied. Available methods to account for misclassification often require the use of a validation sample (i.e. a gold standard). In practice, however, such a gold standard may be unavailable or impractical. We propose a Bayesian approach to adjust for misclassification in a binary covariate in the random effect logistic model when a gold standard is not available. This Markov Chain Monte Carlo (MCMC) approach uses two imperfect measures of a dichotomous exposure under the assumptions of conditional independence and non-differential misclassification. A simulated numerical example and a real clinical example are given to illustrate the proposed approach. Our results suggest that the estimated log odds of inpatient care and the corresponding standard deviation are much larger in our proposed method compared with the models ignoring misclassification. Ignoring misclassification produces downwardly biased estimates and underestimate uncertainty.     

The estimation of gross flows in the presence of measurement error using auxiliary variables

Classification error can lead to substantial biases in the estimation of gross flows from longitudinal data. We propose a method to adjust flow estimates for bias, based on fitting separate multinomial logistic models to the classification error probabilities and the true state transition probabilities using values of auxiliary variables. Our approach has the advantages that it does not require external information on misclassification rates, it permits the identification of factors that are related to misclassification and true transitions and it does not assume independence between classification errors at successive points in time. Constraining the prediction of the stocks to agree with the observed stocks protects against model misspecification. We apply the approach to data on women from the Panel Study of Income Dynamics with three categories of labour force status. The model fitted is shown to have interpretable coefficient estimates and to provide a good fit. Simulation results indicate good performance of the model in predicting the true flows and robustness against departures from the model postulated.     

Variable selection for semiparametric regression models with iterated penalization

Semiparametric regression models with multiple covariates are commonly encountered. When there are covariates not associated with response variable, variable selection may lead to sparser models, more lucid interpretations and more accurate estimation. In this study, we adopt a sieve approach for the estimation of nonparametric covariate effects in semiparametric regression models. We adopt a two-step iterated penalization approach for variable selection. In the first step, a mixture of the Lasso and group Lasso penalties are employed to conduct the first-round variable selection and obtain the initial estimate. In the second step, a mixture of the weighted Lasso and weighted group Lasso penalties, with weights constructed using the initial estimate, are employed for variable selection. We show that the proposed iterated approach has the variable selection consistency property, even when number of unknown parameters diverges with sample size. Numerical studies, including simulation and analysis of a diabetes dataset, show satisfactory performance of the proposed approach.     

Hazards regression for freemium products and services: a competing risks approach

We propose a competing risks approach to analyse customer behaviours in freemium products and services. The event of interest is when a customer starts to pay for additional features or functionalities. The observation of such an event may be preempted by an event where the customer quits using the product before paying and consuming the additional features or functionalities. One such freemium service is the online game category. The Fine-Gray regression model was implemented for an online game player activity data to study how covariates affect the paying hazard. Some covariates are hypothesized to have different discrete effects at multiple change points. We extend the model to allow for possible change points in the analysis.