Disaggregated spatial modelling for areal unit categorical data

Summary.  We consider joint spatial modelling of areal multivariate categorical data assuming a multiway contingency table for the variables, modelled by using a log-linear model, and connected across units by using spatial random effects. With no distinction regarding whether variables are response or explanatory, we do not limit inference to conditional probabilities, as in customary spatial logistic regression. With joint probabilities we can calculate arbitrary marginal and conditional probabilities without having to refit models to investigate different hypotheses. Flexible aggregation allows us to investigate subgroups of interest; flexible conditioning enables not only the study of outcomes given risk factors but also retrospective study of risk factors given outcomes. A benefit of joint spatial modelling is the opportunity to reveal disparities in health in a richer fashion, e.g. across space for any particular group of cells, across groups of cells at a particular location, and, hence, potential space–group interaction. We illustrate with an analysis of birth records for the state of North Carolina and compare with spatial logistic regression.     

Multivariate generalized linear mixed models with random intercepts to analyze cardiovascular risk markers in type-1 diabetic patients

Statistical approaches tailored to analyzing longitudinal data that have multiple outcomes with different distributions are scarce. This paucity is due to the non-availability of multivariate distributions that jointly model outcomes with different distributions other than the multivariate normal. A plethora of research has been done on the specific combination of binary-Gaussian bivariate outcomes but a more general approach that allows other mixtures of distributions for multiple longitudinal outcomes has not been thoroughly demonstrated and examined. Here, we study a multivariate generalized linear mixed models approach that jointly models multiple longitudinal outcomes with different combinations of distributions and incorporates the correlations between the various outcomes through separate yet correlated random intercepts. Every outcome is linked to the set of covariates through a proper link function that allows the incorporation and joint modeling of different distributions. A novel application was demonstrated on a cohort study of Type-1 diabetic patients to jointly model a mix of longitudinal cardiovascular outcomes and to explore for the first time the effect of glycemic control treatment, plasma prekallikrein biomarker, gender and age on cardiovascular risk factors collectively.     

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.     

A general joint model for longitudinal measurements and competing risks survival data with heterogeneous random effects

This article studies a general joint model for longitudinal measurements and competing risks survival data. The model consists of a linear mixed effects sub-model for the longitudinal outcome, a proportional cause-specific hazards frailty sub-model for the competing risks survival data, and a regression sub-model for the variance–covariance matrix of the multivariate latent random effects based on a modified Cholesky decomposition. The model provides a useful approach to adjust for non-ignorable missing data due to dropout for the longitudinal outcome, enables analysis of the survival outcome with informative censoring and intermittently measured time-dependent covariates, as well as joint analysis of the longitudinal and survival outcomes. Unlike previously studied joint models, our model allows for heterogeneous random covariance matrices. It also offers a framework to assess the homogeneous covariance assumption of existing joint models. A Bayesian MCMC procedure is developed for parameter estimation and inference. Its performances and frequentist properties are investigated using simulations. A real data example is used to illustrate the usefulness of the approach.     

An endemic–epidemic beta model for time series of infectious disease proportions

Time series of proportions of infected patients or positive specimens are frequently encountered in disease control and prevention. Since proportions are bounded and often asymmetrically distributed, conventional Gaussian time series models only apply to suitably transformed proportions. Here we borrow both from beta regression and from the well-established HHH model for infectious disease counts to propose an endemic–epidemic beta model for proportion time series. It accommodates the asymmetric shape and heteroskedasticity of proportion distributions and is consistent for complementary proportions. Coefficients can be interpreted in terms of odds ratios. A multivariate formulation with spatial power-law weights enables the joint estimation of model parameters from multiple regions. In our application to a flu activity index in the USA, we find that the endemic–epidemic beta model provides a better fit than a seasonal ARIMA model for the logit-transformed proportions. Furthermore, a multivariate approach can improve regional forecasts and reduce model complexity in comparison to univariate beta models stratified by region.     

The probabilistic reduction approach to specifying multinomial logistic regression models in health outcomes research

The paper provides a novel application of the probabilistic reduction (PR) approach to the analysis of multi-categorical outcomes. The PR approach, which systematically takes account of heterogeneity and functional form concerns, can improve the specification of binary regression models. However, its utility for systematically enriching the specification of and inference from models of multi-categorical outcomes has not been examined, while multinomial logistic regression models are commonly used for inference and, increasingly, prediction. Following a theoretical derivation of the PR-based multinomial logistic model (MLM), we compare functional specification and marginal effects from a traditional specification and a PR-based specification in a model of post-stroke hospital discharge disposition and find that the traditional MLM is misspecified. Results suggest that the impact on the reliability of substantive inferences from a misspecified model may be significant, even when model fit statistics do not suggest a strong lack of fit compared with a properly specified model using the PR approach. We identify situations under which a PR-based MLM specification can be advantageous to the applied researcher.     

Multivariate regression models for discrete and continuous repeated measurements

A general class of multivariate regression models is considered for repeated measurements with discrete and continuous outcome variables. The proposed model is based on the seemingly unrelated regression model (Zellner, 1962) and an extension of the model of Park and Woolson(1992). The regression parameters of the model are consistently estimated using the two-stage least squares method. When the out come variables are multivariate normal, the two-stage estimator reduces to Zellner’s two-stage estimator. As a special case, we consider the marginal distribution described by Liang and Zeger (1986). Under this this distributional assumption, we show that the two-stage estimator has similar asymptotic properties and comparable small sample properties to Liang and Zeger's estimator. Since the proposed approach is based on the least squares method, however, any distributional assumption is not required for variables outcome variables. As a result, the proposed estimator is more robust to the marginal distribution of outcomes.     

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.     

Errors-in-variables beta regression models

Beta regression models provide an adequate approach for modeling continuous outcomes limited to the interval (0, 1). This paper deals with an extension of beta regression models that allow for explanatory variables to be measured with error. The structural approach, in which the covariates measured with error are assumed to be random variables, is employed. Three estimation methods are presented, namely maximum likelihood, maximum pseudo-likelihood and regression calibration. Monte Carlo simulations are used to evaluate the performance of the proposed estimators and the naïve estimator. Also, a residual analysis for beta regression models with measurement errors is proposed. The results are illustrated in a real data set.     

Joint models with multiple longitudinal outcomes and a time-to-event outcome: a corrected two-stage approach

Joint models for longitudinal and survival data have gained a lot of attention in recent years, with the development of myriad extensions to the basic model, including those which allow for multivariate longitudinal data, competing risks and recurrent events. Several software packages are now also available for their implementation. Although mathematically straightforward, the inclusion of multiple longitudinal outcomes in the joint model remains computationally difficult due to the large number of random effects required, which hampers the practical application of this extension. We present a novel approach that enables the fitting of such models with more realistic computational times. The idea behind the approach is to split the estimation of the joint model in two steps: estimating a multivariate mixed model for the longitudinal outcomes and then using the output from this model to fit the survival submodel. So-called two-stage approaches have previously been proposed and shown to be biased. Our approach differs from the standard version, in that we additionally propose the application of a correction factor, adjusting the estimates obtained such that they more closely resemble those we would expect to find with the multivariate joint model. This correction is based on importance sampling ideas. Simulation studies show that this corrected two-stage approach works satisfactorily, eliminating the bias while maintaining substantial improvement in computational time, even in more difficult settings.

     

Small Area Estimation via Multivariate Fay–Herriot Models with Latent Spatial Dependence

The Fay–Herriot model is a standard model for direct survey estimators in which the true quantity of interest, the superpopulation mean, is latent and its estimation is improved through the use of auxiliary covariates. In the context of small area estimation, these estimates can be further improved by borrowing strength across spatial regions or by considering multiple outcomes simultaneously. We provide here two formulations to perform small area estimation with Fay–Herriot models that include both multivariate outcomes and latent spatial dependence. We consider two model formulations. In one of these formulations the outcome‐by‐space dependence structure is separable. The other accounts for the cross dependence through the use of a generalized multivariate conditional autoregressive (GMCAR) structure. The GMCAR model is shown, in a state‐level example, to produce smaller mean square prediction errors, relative to equivalent census variables, than the separable model and the state‐of‐the‐art multivariate model with unstructured dependence between outcomes and no spatial dependence. In addition, both the GMCAR and the separable models give smaller mean squared prediction error than the state‐of‐the‐art model when conducting small area estimation on county level data from the American Community Survey.     

Structural equation models for area health outcomes with model selection

Recent analyses seeking to explain variation in area health outcomes often consider the impact on them of latent measures (i.e. unobserved constructs) of population health risk. The latter are typically obtained by forms of multivariate analysis, with a small set of latent constructs derived from a collection of observed indicators, and a few recent area studies take such constructs to be spatially structured rather than independent over areas. A confirmatory approach is often applicable to the model linking indicators to constructs, based on substantive knowledge of relevant risks for particular diseases or outcomes. In this paper, population constructs relevant to a particular set of health outcomes are derived using an integrated model containing all the manifest variables, namely health outcome variables, as well as indicator variables underlying the latent constructs. A further feature of the approach is the use of variable selection techniques to select significant loadings and factors (especially in terms of effects of constructs on health outcomes), so ensuring parsimonious models are selected. A case study considers suicide mortality and self-harm contrasts in the East of England in relation to three latent constructs: deprivation, fragmentation and urbanicity.     

General location multivariate latent variable models for mixed correlated bounded continuous,ordinal, and nominal responses with non-ignorable missing data

Using a multivariate latent variable approach, this article proposes some new general models to analyze the correlated bounded continuous and categorical (nominal or/and ordinal) responses with and without non-ignorable missing values. First, we discuss regression methods for jointly analyzing continuous, nominal, and ordinal responses that we motivated by analyzing data from studies of toxicity development. Second, using the beta and Dirichlet distributions, we extend the models so that some bounded continuous responses are replaced for continuous responses. The joint distribution of the bounded continuous, nominal and ordinal variables is decomposed into a marginal multinomial distribution for the nominal variable and a conditional multivariate joint distribution for the bounded continuous and ordinal variables given the nominal variable. We estimate the regression parameters under the new general location models using the maximum-likelihood method. Sensitivity analysis is also performed to study the influence of small perturbations of the parameters of the missing mechanisms of the model on the maximal normal curvature. The proposed models are applied to two data sets: BMI, Steatosis and Osteoporosis data and Tehran household expenditure budgets.     

Bayesian density regression for discrete outcomes

We develop Bayesian models for density regression with emphasis on discrete outcomes. The problem of density regression is approached by considering methods for multivariate density estimation of mixed scale variables, and obtaining conditional densities from the multivariate ones. The approach to multivariate mixed scale outcome density estimation that we describe represents discrete variables, either responses or covariates, as discretised versions of continuous latent variables. We present and compare several models for obtaining these thresholds in the challenging context of count data analysis where the response may be over‐ and/or under‐dispersed in some of the regions of the covariate space. We utilise a nonparametric mixture of multivariate Gaussians to model the directly observed and the latent continuous variables. The paper presents a Markov chain Monte Carlo algorithm for posterior sampling, sufficient conditions for weak consistency, and illustrations on density, mean and quantile regression utilising simulated and real datasets.     

Semiparametric Regression Estimation in Copula Models

We consider some methods of semiparametric regression estimation in multivariate models when the common distribution function is represented using a copula and the marginals satisfy a generalized regression model using a transfer functional. Sufficient conditions for consistency and joint asymptotic normality of the finite-dimensional parameters are obtained.     

Accounting for uncertainty in extremal dependence modeling using Bayesian model averaging techniques

Modeling the joint tail of an unknown multivariate distribution can be characterized as modeling the tail of each marginal distribution and modeling the dependence structure between the margins. Classical methods for modeling multivariate extremes are based on the class of multivariate extreme value distributions. However, such distributions do not allow for the possibility of dependence at finite levels that vanishes in the limit. Alternative models have been developed that account for this asymptotic independence, but inferential statistical procedures seeking to combine the classes of asymptotically dependent and asymptotically independent models have been of limited use. We overcome these difficulties by employing Bayesian model averaging to account for both types of asymptotic behavior, and for subclasses within the asymptotically independent framework. Our approach also allows for the calculation of posterior probabilities of different classes of models, allowing for direct comparison between them. We demonstrate the use of joint tail models based on our broader methodology using two oceanographic datasets and a brief simulation study.     

Robust estimation for longitudinal data under outcome‐dependent visit processes

In longitudinal data where the timing and frequency of the measurement of outcomes may be associated with the value of the outcome, significant bias can occur. Previous results depended on correct specification of the outcome process and a somewhat unrealistic visit process model. In practice, this will never exactly be the case, so it is important to understand to what degree the results hold when those assumptions are violated in order to guide practical use of the methods. This paper presents theory and the results of simulation studies to extend our previous work to more realistic visit process models, as well as Poisson outcomes. We also assess the effects of several types of model misspecification. The estimated bias in these new settings generally mirrors the theoretical and simulation results of our previous work and provides confidence in using maximum likelihood methods in practice. Even when the assumptions about the outcome process did not hold, mixed effects models fit by maximum likelihood produced at most small bias in estimated regression coefficients, illustrating the robustness of these methods. This contrasts with generalised estimating equations approaches where bias increased in the settings of this paper. The analysis of data from a study of change in neurological outcomes following microsurgery for a brain arteriovenous malformation further illustrate the results.     

Analyzing dependence in incidence of diabetes and heart problem using generalized bivariate geometric models with covariates

For analyzing incidence data on diabetes and health problems, the bivariate geometric probability distribution is a natural choice but remained unexplored largely due to lack of models linking covariates with the probabilities of bivariate incidence of correlated outcomes. In this paper, bivariate geometric models are proposed for two correlated incidence outcomes. The extended generalized linear models are developed to take into account covariate dependence of the bivariate probabilities of correlated incidence outcomes for diabetes and heart diseases for the elderly population. The estimation and test procedures are illustrated using the Health and Retirement Study data. Two models are shown in this paper, one based on conditional-marginal approach and the other one based on the joint probability distribution with an association parameter. The joint model with association parameter appears to be a very good choice for analyzing the covariate dependence of the joint incidence of diabetes and heart diseases. Bootstrapping is performed to measure the accuracy of estimates and the results indicate very small bias.     

A fuzzy robust regression approach applied to bedload transport data

Fuzzy least-square regression can be very sensitive to unusual data (e.g., outliers). In this article, we describe how to fit an alternative robust-regression estimator in fuzzy environment, which attempts to identify and ignore unusual data. The proposed approach concerns classical robust regression and estimation methods that are insensitive to outliers. In this regard, based on the least trimmed square estimation method, an estimation procedure is proposed for determining the coefficients of the fuzzy regression model for crisp input-fuzzy output data. The investigated fuzzy regression model is applied to bedload transport data forecasting suspended load by discharge based on a real world data. The accuracy of the proposed method is compared with the well-known fuzzy least-square regression model. The comparison results reveal that the fuzzy robust regression model performs better than the other models in suspended load estimation for the particular dataset. This comparison is done based on a similarity measure between fuzzy sets. The proposed model is general and can be used for modeling natural phenomena whose available observations are reported as imprecise rather than crisp.     

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.