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.     

A unified approach to estimating association measures via a joint generalized linear model for paired binary data

Paired binary data arise frequently in biomedical studies with unique features of their own. For instance, in clinical studies involving pairs such as ears, eyes etc., often both the intrapair association parameter and the event probability are of interest. In addition, we may be interested in the dependence of the association parameter on certain covariates as well. Although various methods have been proposed to model paired binary data, this paper proposes a unified approach for estimating various intrapair measures under a generalized linear model with simultaneous maximum likelihood estimates of the marginal probabilities and the intrapair association. The methods are illustrated with a twin morbidity study.     

Logistic regression and other discrete data models for serially correlated observations

Summary We consider the analysis of discrete serially correlated data in the presence of time dependent covariates. If the interest is to relate the covariates to the marginal distribution of the data, Markov chains are an obvious tool to consider, but their use is complicated by the fact that they are expressed in terms of transitional rather than marginal probabilities. We show how to parametrize the transition matrix in a suitable way so that interpretation is as desired. The focus is on binary and Poisson data, but the methodology can be adopted also with other discrete data distributions.     

A generalized linear mixed model for longitudinal binary data with a marginal logit link function

Longitudinal studies of a binary outcome are common in the health, social, and behavioral sciences. In general, a feature of random effects logistic regression models for longitudinal binary data is that the marginal functional form, when integrated over the distribution of the random effects, is no longer of logistic form. Recently, Wang and Louis (2003) proposed a random intercept model in the clustered binary data setting where the marginal model has a logistic form. An acknowledged limitation of their model is that it allows only a single random effect that varies from cluster to cluster. In this paper, we propose a modification of their model to handle longitudinal data, allowing separate, but correlated, random intercepts at each measurement occasion. The proposed model allows for a flexible correlation structure among the random intercepts, where the correlations can be interpreted in terms of Kendall's τ. For example, the marginal correlations among the repeated binary outcomes can decline with increasing time separation, while the model retains the property of having matching conditional and marginal logit link functions. Finally, the proposed method is used to analyze data from a longitudinal study designed to monitor cardiac abnormalities in children born to HIV-infected women.     

A generalized bivariate Bernoulli model with covariate dependence

Dependence in outcome variables may pose formidable difficulty in analyzing data in longitudinal studies. In the past, most of the studies made attempts to address this problem using the marginal models. However, using the marginal models alone, it is difficult to specify the measures of dependence in outcomes due to association between outcomes as well as between outcomes and explanatory variables. In this paper, a generalized approach is demonstrated using both the conditional and marginal models. This model uses link functions to test for dependence in outcome variables. The estimation and test procedures are illustrated with an application to the mobility index data from the Health and Retirement Survey and also simulations are performed for correlated binary data generated from the bivariate Bernoulli distributions. The results indicate the usefulness of the proposed method.     

Regression analysis of longitudinal data with time-dependent covariates in the presence of informative observation and censoring times

In longitudinal observational studies, repeated measures are often correlated with observation times as well as censoring time. This article proposes joint modeling and analysis of longitudinal data with time-dependent covariates in the presence of informative observation and censoring times via a latent variable. Estimating equation approaches are developed for parameter estimation and asymptotic properties of the proposed estimators are established. In addition, a generalization of the semiparametric model with time-varying coefficients for the longitudinal response is considered. Furthermore, a lack-of-fit test is provided for assessing the adequacy of the model, and some tests are presented for investigating whether or not covariate effects vary with time. The finite-sample behavior of the proposed methods is examined in simulation studies, and an application to a bladder cancer study is illustrated.     

Marginalized transition random effect models for multivariate longitudinal binary data

Generalized linear models with random effects and/or serial dependence are commonly used to analyze longitudinal data. However, the computation and interpretation of marginal covariate effects can be difficult. This led Heagerty (1999, 2002) to propose models for longitudinal binary data in which a logistic regression is first used to explain the average marginal response. The model is then completed by introducing a conditional regression that allows for the longitudinal, within‐subject, dependence, either via random effects or regressing on previous responses. In this paper, the authors extend the work of Heagerty to handle multivariate longitudinal binary response data using a triple of regression models that directly model the marginal mean response while taking into account dependence across time and across responses. Markov Chain Monte Carlo methods are used for inference. Data from the Iowa Youth and Families Project are used to illustrate the methods.     

A copula-based Markov chain model for the analysis of binary longitudinal data

A fully parametric first-order autoregressive (AR(1)) model is proposed to analyse binary longitudinal data. By using a discretized version of a copula, the modelling approach allows one to construct separate models for the marginal response and for the dependence between adjacent responses. In particular, the transition model that is focused on discretizes the Gaussian copula in such a way that the marginal is a Bernoulli distribution. A probit link is used to take into account concomitant information in the behaviour of the underlying marginal distribution. Fixed and time-varying covariates can be included in the model. The method is simple and is a natural extension of the AR(1) model for Gaussian series. Since the approach put forward is likelihood-based, it allows interpretations and inferences to be made that are not possible with semi-parametric approaches such as those based on generalized estimating equations. Data from a study designed to reduce the exposure of children to the sun are used to illustrate the methods.     

Marginal and association regression models for longitudinal binary data with drop‐outs: A likelihood‐based approach

Longitudinal data often contain missing observations, and it is in general difficult to justify particular missing data mechanisms, whether random or not, that may be hard to distinguish. The authors describe a likelihood‐based approach to estimating both the mean response and association parameters for longitudinal binary data with drop‐outs. They specify marginal and dependence structures as regression models which link the responses to the covariates. They illustrate their approach using a data set from the Waterloo Smoking Prevention Project They also report the results of simulation studies carried out to assess the performance of their technique under various circumstances.     

Rank repeated measures analysis of covariance

When analyzing a response variable at the presence of both factors and covariates, with potentially correlated responses and violated assumptions of the normal residual or the linear relationship between the response and the covariates, rank-based tests can be an option for inferential procedures instead of the parametric repeated measures analysis of covariance (ANCOVA) models. This article derives a rank-based method for multi-way ANCOVA models with correlated responses. The generalized estimating equations (GEE) technique is employed to construct the proposed rank tests. Asymptotic properties of the proposed tests are derived. Simulation studies confirmed the performance of the proposed tests.     

Multilevel models for repeated binary outcomes: attitudes and voting over the electoral cycle

Models for fitting longitudinal binary responses are explored by using a panel study of voting intentions. A standard multilevel repeated measures logistic model is shown to be inadequate owing to a substantial proportion of respondents who maintain a constant response over time. A multivariate binary response model is shown to be a better fit to the data.     

Hierarchical marginal models with latent uncertainty

In responding to a rating question, an individual may give answers either according to his/her knowledge/awareness or to his/her level of indecision/uncertainty, typically driven by a response style. As ignoring this dual behavior may lead to misleading results, we define a multivariate model for ordinal rating responses by introducing, for every item and every respondent, a binary latent variable that discriminates aware from uncertain responses. Some independence assumptions among latent and observable variables characterize the uncertain behavior and make the model easier to interpret. Uncertain responses are modeled by specifying probability distributions that can depict different response styles. A marginal parameterization allows a simple and direct interpretation of the parameters in terms of association among aware responses and their dependence on explanatory factors. The effectiveness of the proposed model is attested through an application to real data and supported by a Monte Carlo study.     

Exponential class of dynamic binary choice panel data models with fixed effects

ABSTRACT

This paper proposes an exponential class of dynamic binary choice panel data models for the analysis of short T (time dimension) large N (cross section dimension) panel data sets that allow for unobserved heterogeneity (fixed effects) to be arbitrarily correlated with the covariates. The paper derives moment conditions that are invariant to the fixed effects which are then used to identify and estimate the parameters of the model. Accordingly, generalized method of moments (GMM) estimators are proposed that are consistent and asymptotically normally distributed at the root-N rate. We also study the conditional likelihood approach and show that under exponential specification, it can identify the effect of state dependence but not the effects of other covariates. Monte Carlo experiments show satisfactory finite sample performance for the proposed estimators and investigate their robustness to misspecification.     

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.     

Inference in generalized additive mixed modelsby using smoothing splines

Generalized additive mixed models are proposed for overdispersed and correlated data, which arise frequently in studies involving clustered, hierarchical and spatial designs. This class of models allows flexible functional dependence of an outcome variable on covariates by using nonparametric regression, while accounting for correlation between observations by using random effects. We estimate nonparametric functions by using smoothing splines and jointly estimate smoothing parameters and variance components by using marginal quasi-likelihood. Because numerical integration is often required by maximizing the objective functions, double penalized quasi-likelihood is proposed to make approximate inference. Frequentist and Bayesian inferences are compared. A key feature of the method proposed is that it allows us to make systematic inference on all model components within a unified parametric mixed model framework and can be easily implemented by fitting a working generalized linear mixed model by using existing statistical software. A bias correction procedure is also proposed to improve the performance of double penalized quasi-likelihood for sparse data. We illustrate the method with an application to infectious disease data and we evaluate its performance through simulation.     

Marginal Analysis For Clustered Failure Time Data

Clustered failure time data are commonly encountered in biomedical research where the study subjects from the same cluster (e.g., family) share the common genetic and/or environmental factors such that the failure times within the same cluster are correlated. Two approaches that are commonly used to account for the intra-cluster association are frailty models and marginal models. In this paper, we study the marginal proportional hazards model, where the structure of dependence between individuals within a cluster is unspecified. An estimation procedure is developed based on a pseudo-likelihood approach, and a risk set sampling method is proposed for the formulation of the pseudo-likelihood. The asymptotic properties of the proposed estimators are studied, and the related issues regarding the statistical efficiencies are discussed. The performances of the proposed estimator are demonstrated by the simulation studies. A data example from a child vitamin A supplementation trial in Nepal (Nepal Nutrition Intervention Project-Sarlahi, or NNIPS) is used to illustrate this methodology.     

Estimation of dependence between paired correlated failure times in the presence of covariate measurement error

Summary. In many biomedical studies, covariates are subject to measurement error. Although it is well known that the regression coefficients estimators can be substantially biased if the measurement error is not accommodated, there has been little study of the effect of covariate measurement error on the estimation of the dependence between bivariate failure times. We show that the dependence parameter estimator in the Clayton–Oakes model can be considerably biased if the measurement error in the covariate is not accommodated. In contrast with the typical bias towards the null for marginal regression coefficients, the dependence parameter can be biased in either direction. We introduce a bias reduction technique for the bivariate survival function in copula models while assuming an additive measurement error model and replicated measurement for the covariates, and we study the large and small sample properties of the dependence parameter estimator proposed.     

Marginal Projected Multivariate Linear Models for Clustered Angular Data

Among the diverse frameworks that have been proposed for regression analysis of angular data, the projected multivariate linear model provides a particularly appealing and tractable methodology. In this model, the observed directional responses are assumed to correspond to the angles formed by latent bivariate normal random vectors that are assumed to depend upon covariates through a linear model. This implies an angular normal distribution for the observed angles, and incorporates a regression structure through a familiar and convenient relationship. In this paper we extend this methodology to accommodate clustered data (e.g., longitudinal or repeated measures data) by formulating a marginal version of the model and basing estimation on an EM‐like algorithm in which correlation among within‐cluster responses is taken into account by incorporating a working correlation matrix into the M step. A sandwich estimator is used for the parameter estimates’ covariance matrix. The methodology is motivated and illustrated using an example involving clustered measurements of microbril angle on loblolly pine (Pinus taeda L.) Simulation studies are presented that evaluate the finite sample properties of the proposed fitting method. In addition, the relationship between within‐cluster correlation on the latent Euclidean vectors and the corresponding correlation structure for the observed angles is explored.     

Feature screening for case‐cohort studies with failure time outcome

Case‐cohort design has been demonstrated to be an economical and efficient approach in large cohort studies when the measurement of some covariates on all individuals is expensive. Various methods have been proposed for case‐cohort data when the dimension of covariates is smaller than sample size. However, limited work has been done for high‐dimensional case‐cohort data which are frequently collected in large epidemiological studies. In this paper, we propose a variable screening method for ultrahigh‐dimensional case‐cohort data under the framework of proportional model, which allows the covariate dimension increases with sample size at exponential rate. Our procedure enjoys the sure screening property and the ranking consistency under some mild regularity conditions. We further extend this method to an iterative version to handle the scenarios where some covariates are jointly important but are marginally unrelated or weakly correlated to the response. The finite sample performance of the proposed procedure is evaluated via both simulation studies and an application to a real data from the breast cancer study.