Marginal regression models with a time to event outcome and discrete multiple source predictors

Information from multiple informants is frequently used to assess psychopathology. We consider marginal regression models with multiple informants as discrete predictors and a time to event outcome. We fit these models to data from the Stirling County Study; specifically, the models predict mortality from self report of psychiatric disorders and also predict mortality from physician report of psychiatric disorders. Previously, Horton et al. found little relationship between self and physician reports of psychopathology, but that the relationship of self report of psychopathology with mortality was similar to that of physician report of psychopathology with mortality. Generalized estimating equations (GEE) have been used to fit marginal models with multiple informant covariates; here we develop a maximum likelihood (ML) approach and show how it relates to the GEE approach. In a simple setting using a saturated model, the ML approach can be constructed to provide estimates that match those found using GEE. We extend the ML technique to consider multiple informant predictors with missingness and compare the method to using inverse probability weighted (IPW) GEE. Our simulation study illustrates that IPW GEE loses little efficiency compared with ML in the presence of monotone missingness. Our example data has non-monotone missingness; in this case, ML offers a modest decrease in variance compared with IPW GEE, particularly for estimating covariates in the marginal models. In more general settings, e.g., categorical predictors and piecewise exponential models, the likelihood parameters from the ML technique do not have the same interpretation as the GEE. Thus, the GEE is recommended to fit marginal models for its flexibility, ease of interpretation and comparable efficiency to ML in the presence of missing data.     

Least squares estimation of regression parameters in mixed effects models with unmeasured covariates

We consider mixed effects models for longitudinal, repeated measures or clustered data. Unmeasured or omitted covariates in such models may be correlated with the included covanates, and create model violations when not taken into account. Previous research and experience with longitudinal data sets suggest a general form of model which should be considered when omitted covariates are likely, such as in observational studies. We derive the marginal model between the response variable and included covariates, and consider model fitting using the ordinary and weighted least squares methods, which require simple non-iterative computation and no assumptions on the distribution of random covariates or error terms, Asymptotic properties of the least squares estimators are also discussed. The results shed light on the structure of least squares estimators in mixed effects models, and provide large sample procedures for statistical inference and prediction based on the marginal model. We present an example of the relationship between fluid intake and output in very low birth weight infants, where the model is found to have the assumed structure.     

Marginal methods for clustered longitudinal binary data with incomplete covariates

Many analyses for incomplete longitudinal data are directed to examining the impact of covariates on the marginal mean responses. We consider the setting in which longitudinal responses are collected from individuals nested within clusters. We discuss methods for assessing covariate effects on the mean and association parameters when covariates are incompletely observed. Weighted first and second order estimating equations are constructed to obtain consistent estimates of mean and association parameters when covariates are missing at random. Empirical studies demonstrate that estimators from the proposed method have negligible finite sample biases in moderate samples. An application to the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) demonstrates the utility of the proposed method.     

A Bayesian model for measurement and misclassification errors alongside missing data,with an application to higher education participation in Australia

In this paper we consider the impact of both missing data and measurement errors on a longitudinal analysis of participation in higher education in Australia. We develop a general method for handling both discrete and continuous measurement errors that also allows for the incorporation of missing values and random effects in both binary and continuous response multilevel models. Measurement errors are allowed to be mutually dependent and their distribution may depend on further covariates. We show that our methodology works via two simple simulation studies. We then consider the impact of our measurement error assumptions on the analysis of the real data set.     

Markov structure based logistic regression for repeated measures: An application to diabetes mellitus data

In longitudinal studies, as repeated observations are made on the same individual the response variables will usually be correlated. In analyzing such data, this dependence must be taken into account to avoid misleading inferences. The focus of this paper is to apply a logistic marginal model with Markovian dependence proposed by Azzalini [A. Azzalini, Logistic regression for autocorrelated data with application to repeated measures, Biometrika 81 (1994) 767–775] to the study of the influence of time-dependent covariates on the marginal distribution of the binary response in serially correlated binary data. We have shown how to construct the model so that the covariates relate only to the mean value of the process, independent of the association parameters. After formulating the proposed model for repeated measures data, the same approach is applied to missing data. An application is provided to the diabetes mellitus data of registered patients at the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) in 1984, using both time stationary and time varying covariates.     

Restricted alternatives tests in a bivariate exponential model with covariates

This paper is about the analysis of paired survival data using the exponential bivariate model of Sarkar for the underlying survival times, (X,Y), subject to censoring. Under this parametric model we test parameters in the presence of covariates. We consider first, tests of hypotheses of independence and equality of survival marginals, and second, test of hypotheses of covariate effects and survival superiority of one marginal over the other are considered. For this last question we applied a statistical test based on the Union-intersection principle.     

Modeling the Agreement of Discrete Bivariate Survival Times using Kappa Coefficient

Using local kappa coefficients, we develop a method to assess the agreement between two discrete survival times that are measured on the same subject by different raters or methods. We model the marginal distributions for the two event times and local kappa coefficients in terms of covariates. An estimating equation is used for modeling the marginal distributions and a pseudo-likelihood procedure is used to estimate the parameters in the kappa model. The performance of the estimation procedure is examined through simulations. The proposed method can be extended to multivariate discrete survival distributions.     

Vector-borne infectious disease mapping with stochastic difference equations: an analysis of dengue disease in Malaysia

Few publications consider the estimation of relative risk for vector-borne infectious diseases. Most of these articles involve exploratory analysis that includes the study of covariates and their effects on disease distribution and the study of geographic information systems to integrate patient-related information. The aim of this paper is to introduce an alternative method of relative risk estimation based on discrete time–space stochastic SIR-SI models (susceptible–infective–recovered for human populations; susceptible–infective for vector populations) for the transmission of vector-borne infectious diseases, particularly dengue disease. First, we describe deterministic compartmental SIR-SI models that are suitable for dengue disease transmission. We then adapt these to develop corresponding discrete time–space stochastic SIR-SI models. Finally, we develop an alternative method of estimating the relative risk for dengue disease mapping based on these models and apply them to analyse dengue data from Malaysia. This new approach offers a better model for estimating the relative risk for dengue disease mapping compared with the other common approaches, because it takes into account the transmission process of the disease while allowing for covariates and spatial correlation between risks in adjacent regions.     

Bayesian analysis for zero-or-one inflated proportion data using quantile regression

In this paper, we propose the use of Bayesian quantile regression for the analysis of proportion data. We also consider the case when the data present a zero-or-one inflation using a two-part model approach. For the latter scheme, we assume that the response variable is generated by a mixed discrete–continuous distribution with a point mass at zero or one. Quantile regression is then used to explain the conditional distribution of the continuous part between zero and one, while the mixture probability is also modelled as a function of the covariates. We check the performance of these models with two simulation studies. We illustrate the method with data about the proportion of households with access to electricity in Brazil.     

Cure rate survival models with missing covariates: a simulation study

In this paper we study the cure rate survival model involving a competitive risk structure with missing categorical covariates. A parametric distribution that can be written as a sequence of one-dimensional conditional distributions is specified for the missing covariates. We consider the missing data at random situation so that the missing covariates may depend only on the observed ones. Parameter estimates are obtained by using the EM algorithm via the method of weights. Extensive simulation studies are conducted and reported to compare estimates efficiency with and without missing data. As expected, the estimation approach taking into consideration the missing covariates presents much better efficiency in terms of mean square errors than the complete case situation. Effects of increasing cured fraction and censored observations are also reported. We demonstrate the proposed methodology with two real data sets. One involved the length of time to obtain a BS degree in Statistics, and another about the time to breast cancer recurrence.     

Adaptive Isotonic Estimation of the Minimum Effective and Peak Doses in the Presence of Covariates

We consider a problem of estimating the minimum effective and peak doses in the presence of covariates. We propose a sequential strategy for subject assignment that includes an adaptive randomization component to balance the allocation to placebo and active doses with respect to covariates. We conclude that either adjusting for covariates in the model or balancing allocation with respect to covariates is required to avoid bias in the target dose estimation. We also compute optimal allocation to estimate the minimum effective and peak doses in discrete dose space using isotonic regression.     

On maximum likelihood estimation in parametric regression with missing covariates

We consider parametric regression problems with some covariates missing at random. It is shown that the regression parameter remains identifiable under natural conditions. When the always observed covariates are discrete, we propose a semiparametric maximum likelihood method, which does not require parametric specification of the missing data mechanism or the covariate distribution. The global maximum likelihood estimator (MLE), which maximizes the likelihood over the whole parameter set, is shown to exist under simple conditions. For ease of computation, we also consider a restricted MLE which maximizes the likelihood over covariate distributions supported by the observed values. Under regularity conditions, the two MLEs are asymptotically equivalent and strongly consistent for a class of topologies on the parameter set.     

A more general methodology for fitting global cross-ratio models for discrete longitudinal responses

In this paper, we focus on repeated measurement problems, comprising an interesting research area in statistics. We study longitudinal data which arise when outcomes are observed repeatedly on each experimental subject at several points. We focus on a marginal approach for this type of data with lack of independence among the observations proposed by Dale [Global cross-ratio models for bivariate, discrete, ordered responses. Biometrics. 1986;42(4):909–917] for bivariate, discrete, ordered responses. We propose an alternative estimation based on divergence measures to the full likelihood method proposed in that paper. Finally, a wide simulation study and a data example that illustrates the new methodology is provided.     

Variable selection in heterogeneous panel data models with cross-sectional dependence

This paper studies the Bridge estimator for a high-dimensional panel data model with heterogeneous varying coefficients, where the random errors are assumed to be serially correlated and cross-sectionally dependent. We establish oracle efficiency and the asymptotic distribution of the Bridge estimator, when the number of covariates increases to infinity with the sample size in both dimensions. A BIC-type criterion is also provided for tuning parameter selection. We further generalise the marginal Bridge estimator for our model to asymptotically correctly identify the covariates with zero coefficients even when the number of covariates is greater than the sample size under a partial orthogonality condition. The finite sample performance of the proposed estimator is demonstrated by simulated data examples, and an empirical application with the US stock dataset is also provided.     

Identification of average marginal effects under misspecification when covariates are normal

A previously known result in the econometrics literature is that when covariates of an underlying data generating process are jointly normally distributed, estimates from a nonlinear model that is misspecified as linear can be interpreted as average marginal effects. This has been shown for models with exogenous covariates and separability between covariates and errors. In this paper, we extend this identification result to a variety of more general cases, in particular for combinations of separable and nonseparable models under both exogeneity and endogeneity. So long as the underlying model belongs to one of these large classes of data generating processes, our results show that nothing else must be known about the true DGP—beyond normality of observable data, a testable assumption—in order for linear estimators to be interpretable as average marginal effects. We use simulation to explore the performance of these estimators using a misspecified linear model and show they perform well when the data are normal but can perform poorly when this is not the case.     

Identification of longitudinal biomarkers for survival by a score test derived from a joint model of longitudinal and competing risks data

In this paper, we consider joint modelling of repeated measurements and competing risks failure time data. For competing risks time data, a semiparametric mixture model in which proportional hazards model are specified for failure time models conditional on cause and a multinomial model for the marginal distribution of cause conditional on covariates. We also derive a score test based on joint modelling of repeated measurements and competing risks failure time data to identify longitudinal biomarkers or surrogates for a time to event outcome in competing risks data.     

Double robust estimation in longitudinal marginal structural models

In this article we consider estimation of causal parameters in a marginal structural model for the discrete intensity of the treatment specific counting process (e.g. hazard of a treatment specific survival time) based on longitudinal observational data on treatment, covariates and survival. We define three estimators: the inverse probability of treatment weighted (IPTW) estimator, the maximum likelihood estimator (MLE), and a double robust (DR) estimator. The DR estimator is obtained by following a general methodology for constructing double robust estimating functions in censored data models as described in van der Laan and Robins (Unified Methods for Censored Longitudinal Data and Causality, 2002). The double-robust estimator is consistent and asymptotically linear when either the treatment mechanism or the partial likelihood of the observed data is consistently estimated. We illustrate the superiority of the DR estimator relative to the IPTW and ML estimators in a simulation study. The proposed methodology is also applied to estimate the causal effect of exercise on physical functioning in a longitudinal study of seniors in Sonoma County.     

Semiparametric efficient estimation for the auxiliary outcome problem with the conditional mean model

The authors consider semiparametric efficient estimation of parameters in the conditional mean model for a simple incomplete data structure in which the outcome of interest is observed only for a random subset of subjects but covariates and surrogate (auxiliary) outcomes are observed for all. They use optimal estimating function theory to derive the semiparametric efficient score in closed form. They show that when covariates and auxiliary outcomes are discrete, a Horvitz‐Thompson type estimator with empirically estimated weights is semiparametric efficient. The authors give simulation studies validating the finite‐sample behaviour of the semiparametric efficient estimator and its asymptotic variance; they demonstrate the efficiency of the estimator in realistic settings.     

Marginal Regression of Gaps Between Recurrent Events

Recurrent event data typically exhibit the phenomenon of intra-individual correlation, owing to not only observed covariates but also random effects. In many applications, the population may be reasonably postulated as a heterogeneous mixture of individual renewal processes, and the inference of interest is the effect of individual-level covariates. In this article, we suggest and investigate a marginal proportional hazards model for gaps between recurrent events. A connection is established between observed gap times and clustered survival data with informative cluster size. We subsequently construct a novel and general inference procedure for the latter, based on a functional formulation of standard Cox regression. Large-sample theory is established for the proposed estimators. Numerical studies demonstrate that the procedure performs well with practical sample sizes. Application to the well-known bladder tumor data is given as an illustration.     

Regression in a copula model for bivariate count data

In many cases of modeling bivariate count data, the interest lies on studying the association rather than the marginal properties. We form a flexible regression copula-based model where covariates are used not only for the marginal but also for the copula parameters. Since copula measures the association, the use of covariates in its parameters allow for direct modeling of association. A real-data application related to transaction market basket data is used. Our goal is to refine and understand whether the association between the number of purchases of certain product categories depends on particular demographic customers’ characteristics. Such information is important for decision making for marketing purposes.