Latent class models for utilisation of health care

This paper explores different approaches to econometric modelling of count measures of health care utilisation, with an emphasis on latent class models. A new model is proposed that combines the features of the two most common approaches: the hurdle model and the finite mixture negative binomial. Additionally, the panel structure of the data is taken into account. The proposed finite mixture hurdle model is shown to fit the data substantially better than the existing models for a particular application to data from the RAND Health Insurance Experiment. The estimation results indicate a higher price effect for low users of health care. It is furthermore found that this results mainly from the difference of the price effects on the probability to visit a doctor, while the price effect on the conditional number of visits does not differ significantly between high and low users.     

Time‐varying effect models for ordinal responses with applications in substance abuse research

Ordinal responses are very common in longitudinal data collected from substance abuse research or other behavioral research. This study develops a new statistical model with free SAS macros that can be applied to characterize time‐varying effects on ordinal responses. Our simulation study shows that the ordinal‐scale time‐varying effects model has very low estimation bias and sometimes offers considerably better performance when fitting data with ordinal responses than a model that treats the response as continuous. Contrary to a common assumption that an ordinal scale with several levels can be treated as continuous, our results indicate that it is not so much the number of levels on the ordinal scale but rather the skewness of the distribution that makes a difference on relative performance of linear versus ordinal models. We use longitudinal data from a well‐known study on youth at high risk for substance abuse as a motivating example to demonstrate that the proposed model can characterize the time‐varying effect of negative peer influences on alcohol use in a way that is more consistent with the developmental theory and existing literature, in comparison with the linear time‐varying effect model. Copyright © 2014 John Wiley & Sons, Ltd.     

Flexible bivariate correlated count data regression

Multivariate count data are common in many disciplines. The variables in such data often exhibit complex positive or negative dependency structures. We propose three Bayesian approaches to modeling bivariate count data by simultaneously considering covariate-dependent means and correlation. A direct approach utilizes a bivariate negative binomial probability mass function developed in Famoye (2010, Journal of Applied Statistics). The second approach fits bivariate count data indirectly using a bivariate Poisson-gamma mixture model. The third approach is a bivariate Gaussian copula model. Based on the results from simulation analyses, the indirect and copula approaches perform better overall than the direct approach in terms of model fitting and identifying covariate-dependent association. The proposed approaches are applied to two RNA-sequencing data sets for studying breast cancer and melanoma (BRCA-US and SKCM-US), respectively, obtained through the International Cancer Genome Consortium.     

A goodness‐of‐fit test for the proportional odds regression model

We examine goodness‐of‐fit tests for the proportional odds logistic regression model—the most commonly used regression model for an ordinal response variable. We derive a test statistic based on the Hosmer–Lemeshow test for binary logistic regression. Using a simulation study, we investigate the distribution and power properties of this test and compare these with those of three other goodness‐of‐fit tests. The new test has lower power than the existing tests; however, it was able to detect a greater number of the different types of lack of fit considered in this study. Moreover, the test allows for the results to be summarized in a contingency table of observed and estimated frequencies, which is a useful supplementary tool to assess model fit. We illustrate the ability of the tests to detect lack of fit using a study of aftercare decisions for psychiatrically hospitalized adolescents. The test proposed in this paper is similar to a recently developed goodness‐of‐fit test for multinomial logistic regression. A unified approach for testing goodness of fit is now available for binary, multinomial, and ordinal logistic regression models. Copyright © 2012 John Wiley & Sons, Ltd.     

L1 penalized continuation ratio models for ordinal response prediction using high-dimensional datasets

Health status and outcomes are frequently measured on an ordinal scale. For high-throughput genomic datasets, the common approach to analyzing ordinal response data has been to break the problem into one or more dichotomous response analyses. This dichotomous response approach does not make use of all available data and therefore leads to loss of power and increases the number of type I errors. Herein we describe an innovative frequentist approach that combines two statistical techniques, L(1) penalization and continuation ratio models, for modeling an ordinal response using gene expression microarray data. We conducted a simulation study to assess the performance of two computational approaches and two model selection criteria for fitting frequentist L(1) penalized continuation ratio models. Moreover, we empirically compared the approaches using three application datasets, each of which seeks to classify an ordinal class using microarray gene expression data as the predictor variables. We conclude that the L(1) penalized constrained continuation ratio model is a useful approach for modeling an ordinal response for datasets where the number of covariates (p) exceeds the sample size (n) and the decision of whether to use Akaike Information Criterion (AIC) or Bayesian Information Criterion (BIC) for selecting the final model should depend upon the similarities between the pathologies underlying the disease states to be classified.     

Identifying and interpreting subgroups in health care utilization data with count mixture regression models

Inpatient care is a large share of total health care spending, making analysis of inpatient utilization patterns an important part of understanding what drives health care spending growth. Common features of inpatient utilization measures such as length of stay and spending include zero inflation, overdispersion, and skewness, all of which complicate statistical modeling. Moreover, latent subgroups of patients may have distinct patterns of utilization and relationships between that utilization and observed covariates. In this work, we apply and compare likelihood-based and parametric Bayesian mixtures of negative binomial and zero-inflated negative binomial regression models. In a simulation, we find that the Bayesian approach finds the true number of mixture components more accurately than using information criteria to select among likelihood-based finite mixture models. When we apply the models to data on hospital lengths of stay for patients with lung cancer, we find distinct subgroups of patients with different means and variances of hospital days, health and treatment covariates, and relationships between covariates and length of stay.     

A Bayesian approach to adjust for diagnostic misclassification between two mortality causes in Poisson regression

Response misclassification of counted data biases and understates the uncertainty of parameter estimators in Poisson regression models. To correct these problems, researchers have devised classical procedures that rely on asymptotic distribution results and supplemental validation data in order to estimate unknown misclassification parameters. We derive a new Bayesian Poisson regression procedure that accounts and corrects for misclassification for a count variable with two categories. Under the Bayesian paradigm, one can use validation data, expert opinion, or a combination of these two approaches to correct for the consequences of misclassification. The Bayesian procedure proposed here yields an operationally effective way to correct and account for misclassification effects in Poisson count regression models. We demonstrate the performance of the model in a simulation study. Additionally, we analyze two real-data examples and compare our new Bayesian inference method that adjusts for misclassification with a similar analysis that ignores misclassification.     

On performance of parametric and distribution‐free models for zero‐inflated and over‐dispersed count responses

Zero‐inflated Poisson (ZIP) and negative binomial (ZINB) models are widely used to model zero‐inflated count responses. These models extend the Poisson and negative binomial (NB) to address excessive zeros in the count response. By adding a degenerate distribution centered at 0 and interpreting it as describing a non‐risk group in the population, the ZIP (ZINB) models a two‐component population mixture. As in applications of Poisson and NB, the key difference between ZIP and ZINB is the allowance for overdispersion by the ZINB in its NB component in modeling the count response for the at‐risk group. Overdispersion arising in practice too often does not follow the NB, and applications of ZINB to such data yield invalid inference. If sources of overdispersion are known, other parametric models may be used to directly model the overdispersion. Such models too are subject to assumed distributions. Further, this approach may not be applicable if information about the sources of overdispersion is unavailable. In this paper, we propose a distribution‐free alternative and compare its performance with these popular parametric models as well as a moment‐based approach proposed by Yu et al. [Statistics in Medicine 2013; 32 : 2390–2405]. Like the generalized estimating equations, the proposed approach requires no elaborate distribution assumptions. Compared with the approach of Yu et al., it is more robust to overdispersed zero‐inflated responses. We illustrate our approach with both simulated and real study data. Copyright © 2015 John Wiley & Sons, Ltd.     

Parametric robust inferences for correlated ordinal data

The aim of this article is to provide asymptotically valid likelihood inferences about regression parameters for correlated ordinal response variables. The legitimacy of this novel approach requires no knowledge of the underlying joint distributions so long as their second moments exist. The efficacy of the proposed parametric approach is demonstrated via simulations and the analyses of two real data sets.     

A goodness‐of‐fit test for the ordered stereotype model

This paper presents a new goodness‐of‐fit test for an ordered stereotype model used for an ordinal response variable. The proposed test is based on the well‐known Hosmer–Lemeshow test and its version for the proportional odds regression model. The latter test statistic is calculated from a grouping scheme assuming that the levels of the ordinal response are equally spaced which might be not true. One of the main advantages of the ordered stereotype model is that it allows us to determine a new uneven spacing of the ordinal response categories, dictated by the data. The proposed test takes the use of this new adjusted spacing to partition data. A simulation study shows good performance of the proposed test under a variety of scenarios. Finally, the results of the application in two examples are presented. Copyright © 2016 John Wiley & Sons, Ltd.     

零膨胀模型在心肌缺血节段数影响因素研究中的应用

目的讨论零膨胀模型在计数资料中的应用。方法应用零膨胀负二项模型分析冠心病患者心肌缺血节段数的影响因素。结果零膨胀负二项模型logit部分结果表明没有家族史、年龄越小、左室收缩末容积越小的患者发生心肌节段缺血的可能性较小;负二项部分结果表明有糖尿病史、有冠心病家族史、左室收缩末容积越大的患者发生心肌缺血节段数越多。结论当计数资料存在过多零计数时,应用零过多模型能够得到很好的拟合效果。     

Marginalized models for longitudinal ordinal data with application to quality of life studies

Random effects are often used in generalized linear models to explain the serial dependence for longitudinal categorical data. Marginalized random effects models (MREMs) for the analysis of longitudinal binary data have been proposed to permit likelihood-based estimation of marginal regression parameters. In this paper, we propose a model to extend the MREM to accommodate longitudinal ordinal data. Maximum marginal likelihood estimation is proposed utilizing quasi-Newton algorithms with Monte Carlo integration of the random effects. Our approach is applied to analyze the quality of life data from a recent colorectal cancer clinical trial. Dropout occurs at a high rate and is often due to tumor progression or death. To deal with events due to progression/death, we used a mixture model for the joint distribution of longitudinal measures and progression/death times and use principal stratification to draw causal inferences about survivors.     

Sample size calculation for comparing two negative binomial rates

Negative binomial model has been increasingly used to model the count data in recent clinical trials. It is frequently chosen over Poisson model in cases of overdispersed count data that are commonly seen in clinical trials. One of the challenges of applying negative binomial model in clinical trial design is the sample size estimation. In practice, simulation methods have been frequently used for sample size estimation. In this paper, an explicit formula is developed to calculate sample size based on the negative binomial model. Depending on different approaches to estimate the variance under null hypothesis, three variations of the sample size formula are proposed and discussed. Important characteristics of the formula include its accuracy and its ability to explicitly incorporate dispersion parameter and exposure time. The performance of the formula with each variation is assessed using simulations. Copyright © 2013 John Wiley & Sons, Ltd.     

Joint modeling of longitudinal ordinal data and competing risks survival times and analysis of the NINDS rt‐PA stroke trial

Existing joint models for longitudinal and survival data are not applicable for longitudinal ordinal outcomes with possible non‐ignorable missing values caused by multiple reasons. We propose a joint model for longitudinal ordinal measurements and competing risks failure time data, in which a partial proportional odds model for the longitudinal ordinal outcome is linked to the event times by latent random variables. At the survival endpoint, our model adopts the competing risks framework to model multiple failure types at the same time. The partial proportional odds model, as an extension of the popular proportional odds model for ordinal outcomes, is more flexible and at the same time provides a tool to test the proportional odds assumption. We use a likelihood approach and derive an EM algorithm to obtain the maximum likelihood estimates of the parameters. We further show that all the parameters at the survival endpoint are identifiable from the data. Our joint model enables one to make inference for both the longitudinal ordinal outcome and the failure times simultaneously. In addition, the inference at the longitudinal endpoint is adjusted for possible non‐ignorable missing data caused by the failure times. We apply the method to the NINDS rt‐PA stroke trial. Our study considers the modified Rankin Scale only. Other ordinal outcomes in the trial, such as the Barthel and Glasgow scales, can be treated in the same way. Copyright © 2009 John Wiley & Sons, Ltd.     

A practical approach to computing power for generalized linear models with nominal, count, or ordinal responses

Data analysts facing study design questions on a regular basis could derive substantial benefit from a straightforward and unified approach to power calculations for generalized linear models. Many current proposals for dealing with binary, ordinal, or count outcomes are conceptually or computationally demanding, limited in terms of accommodating covariates, and/or have not been extensively assessed for accuracy assuming moderate sample sizes. Here, we present a simple method for estimating conditional power that requires only standard software for fitting the desired generalized linear model for a non-continuous outcome. The model is fit to an appropriate expanded data set using easily calculated weights that represent response probabilities given the assumed values of the parameters. The variance-covariance matrix resulting from this fit is then used in conjunction with an established non-central chi square approximation to the distribution of the Wald statistic. Alternatively, the model can be re-fit under the null hypothesis to approximate power based on the likelihood ratio statistic. We provide guidelines for constructing a representative expanded data set to allow close approximation of unconditional power based on the assumed joint distribution of the covariates. Relative to prior proposals, the approach proves particularly flexible for handling one or more continuous covariates without any need for discretizing. We illustrate the method for a variety of outcome types and covariate patterns, using simulations to demonstrate its accuracy for realistic sample sizes.     

A Bayesian analysis of bivariate ordinal data: Wisconsin epidemiologic study of diabetic retinopathy revisited

In many biomedical experiments one may often encounter bivariate data which are component-wise ordinal. The data set of the ophthalmologic experiment of the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) is an example of such data. Several authors considered the analysis of such data from different viewpoints. The present work reviews the existing literature based on the WESDR data and on the basis of some latent variables provide the technique for analysing such data more easily in a Bayesian framework. Computation supports the methodology to a great extent. A comparison between our approach and the likelihood based approach considered by Kim has also been made.     

Sample size calculation for clinical trials with correlated count measurements based on the negative binomial distribution

Statistical inference based on correlated count measurements are frequently performed in biomedical studies. Most of existing sample size calculation methods for count outcomes are developed under the Poisson model. Deviation from the Poisson assumption (equality of mean and variance) has been widely documented in practice, which indicates urgent needs of sample size methods with more realistic assumptions to ensure valid experimental design. In this study, we investigate sample size calculation for clinical trials with correlated count measurements based on the negative binomial distribution. This approach is flexible to accommodate overdispersion and unequal measurement intervals, as well as arbitrary randomization ratios, missing data patterns, and correlation structures. Importantly, the derived sample size formulas have closed forms both for the comparison of slopes and for the comparison of time-averaged responses, which greatly reduces the burden of implementation in practice. We conducted extensive simulation to demonstrate that the proposed method maintains the nominal levels of power and type I error over a wide range of design configurations. We illustrate the application of this approach using a real epileptic trial.     

Marginalized zero‐inflated negative binomial regression with application to dental caries

The zero‐inflated negative binomial regression model (ZINB) is often employed in diverse fields such as dentistry, health care utilization, highway safety, and medicine to examine relationships between exposures of interest and overdispersed count outcomes exhibiting many zeros. The regression coefficients of ZINB have latent class interpretations for a susceptible subpopulation at risk for the disease/condition under study with counts generated from a negative binomial distribution and for a non‐susceptible subpopulation that provides only zero counts. The ZINB parameters, however, are not well‐suited for estimating overall exposure effects, specifically, in quantifying the effect of an explanatory variable in the overall mixture population. In this paper, a marginalized zero‐inflated negative binomial regression (MZINB) model for independent responses is proposed to model the population marginal mean count directly, providing straightforward inference for overall exposure effects based on maximum likelihood estimation. Through simulation studies, the finite sample performance of MZINB is compared with marginalized zero‐inflated Poisson, Poisson, and negative binomial regression. The MZINB model is applied in the evaluation of a school‐based fluoride mouthrinse program on dental caries in 677 children. Copyright © 2015 John Wiley & Sons, Ltd.     

Disease mapping via negative binomial regression M‐quantiles

We introduce a semi‐parametric approach to ecological regression for disease mapping, based on modelling the regression M‐quantiles of a negative binomial variable. The proposed method is robust to outliers in the model covariates, including those due to measurement error, and can account for both spatial heterogeneity and spatial clustering. A simulation experiment based on the well‐known Scottish lip cancer data set is used to compare the M‐quantile modelling approach with a disease mapping approach based on a random effects model. This suggests that the M‐quantile approach leads to predicted relative risks with smaller root mean square error. The paper concludes with an illustrative application of the M‐quantile approach, mapping low birth weight incidence data for English Local Authority Districts for the years 2005–2010. Copyright © 2014 John Wiley & Sons, Ltd.     

A flexible family of transformation cure rate models

In this paper, we introduce a flexible family of cure rate models, mainly motivated by the biological derivation of the classical promotion time cure rate model and assuming that a metastasis‐competent tumor cell produces a detectable‐tumor mass only when a specific number of distinct biological factors affect the cell. Special cases of the new model are, among others, the promotion time (proportional hazards), the geometric (proportional odds), and the negative binomial cure rate model. In addition, our model generalizes specific families of transformation cure rate models and some well‐studied destructive cure rate models. Exact likelihood inference is carried out by the aid of the expectation?maximization algorithm; a profile likelihood approach is exploited for estimating the parameters of the model while model discrimination problem is analyzed by the aid of the likelihood ratio test. A simulation study demonstrates the accuracy of the proposed inferential method. Finally, as an illustration, we fit the proposed model to a cutaneous melanoma data‐set. Copyright © 2017 John Wiley & Sons, Ltd.