Longitudinal Data Estimating Equations for Dispersion Models

Liang & Zeger's generalized estimating equation approach for analysis of longitudinal data is extended to marginal distributions of dispersion model type. This includes for example the von Mises and simplex distributions, suitable for angles and proportions, respectively. Both modelling of position and joint modelling of position and dispersion is considered, and the method is applied to a set of bird orientation data.     

Local Influence in Generalized Estimating Equations

Abstract.  We investigate the influence of subjects or observations on regression coefficients of generalized estimating equations (GEEs) using local influence. The GEE approach does not require the full multivariate distribution of the response vector. We extend the likelihood displacement to a quasi-likelihood displacement, and propose local influence diagnostics under several perturbation schemes. An illustrative example in GEEs is given and we compare the results using the local influence and deletion methods.     

An Autoregressive Model for Time Series of Circular Data

This article focuses on estimating an autoregressive regression model for circular time series data. Simulation studies have shown the difficulties involved in obtaining good estimates from low concentration data or from small samples. It presents an application using real data.     

Partial Linear Models for Longitudinal Data Based on Quadratic Inference Functions

In this paper, we consider improved estimating equations for semiparametric partial linear models (PLM) for longitudinal data, or clustered data in general. We approximate the non‐parametric function in the PLM by a regression spline, and utilize quadratic inference functions (QIF) in the estimating equations to achieve a more efficient estimation of the parametric part in the model, even when the correlation structure is misspecified. Moreover, we construct a test which is an analogue to the likelihood ratio inference function for inferring the parametric component in the model. The proposed methods perform well in simulation studies and real data analysis conducted in this paper.     

Model Selection Criterion Based on the Multivariate Quasi‐Likelihood for Generalized Estimating Equations

The generalized estimating equations (GEE) approach has attracted considerable interest for the analysis of correlated response data. This paper considers the model selection criterion based on the multivariate quasi‐likelihood (MQL) in the GEE framework. The GEE approach is closely related to the MQL. We derive a necessary and sufficient condition for the uniqueness of the risk function based on the MQL by using properties of differential geometry. Furthermore, we establish a formal derivation of model selection criterion as an asymptotically unbiased estimator of the prediction risk under this condition, and we explicitly take into account the effect of estimating the correlation matrix used in the GEE procedure.     

Sampling Adjusted Analysis of Dynamic Additive Regression Models for Longitudinal Data

We consider a modelling approach to longitudinal data that aims at estimating flexible covariate effects in a model where the sampling probabilities are modelled explicitly. The joint modelling yields simple estimators that are easy to compute and analyse, even if the sampling of the longitudinal responses interacts with the response level. An incorrect model for the sampling probabilities results in biased estimates. Non-representative sampling occurs, for example, if patients with an extreme development (based on extreme values of the response) are called in for additional examinations and measurements. We allow covariate effects to be time-varying or time-constant. Estimates of covariate effects are obtained by solving martingale equations locally for the cumulative regression functions. Using Aalen's additive model for the sampling probabilities, we obtain simple expressions for the estimators and their asymptotic variances. The asymptotic distributions for the estimators of the non-parametric components as well as the parametric components of the model are derived drawing on general martingale results. Two applications are presented. We consider the growth of cystic fibrosis patients and the prothrombin index for liver cirrhosis patients. The conclusion about the growth of the cystic fibrosis patients is not altered when adjusting for a possible non-representativeness in the sampling, whereas we reach substantively different conclusions about the treatment effect for the liver cirrhosis patients.     

Criterion for the Selection of a Working Correlation Structure in the Generalized Estimating Equation Approach for Longitudinal Balanced Data

The generalized estimating equation is a popular method for analyzing correlated response data. It is important to determine a proper working correlation matrix at the time of applying the generalized estimating equation since an improper selection sometimes results in inefficient parameter estimates. We propose a criterion for the selection of an appropriate working correlation structure. The proposed criterion is based on a statistic to test the hypothesis that the covariance matrix equals a given matrix, and also measures the discrepancy between the covariance matrix estimator and the specified working covariance matrix. We evaluated the performance of the proposed criterion through simulation studies assuming that for each subject, the number of observations remains the same. The results revealed that when the proposed criterion was adopted, the proportion of selecting a true correlation structure was generally higher than that when other competing approaches were adopted. The proposed criterion was applied to longitudinal wheeze data, and it was suggested that the resultant correlation structure was the most accurate.     

A Generalized Estimating Equations Approach for Analysis of the Impact of New Technology on a Trawl Fishery

The article describes a generalized estimating equations approach that was used to investigate the impact of technology on vessel performance in a trawl fishery during 1988–96, while accounting for spatial and temporal correlations in the catch-effort data. Robust estimation of parameters in the presence of several levels of clustering depended more on the choice of cluster definition than on the choice of correlation structure within the cluster. Models with smaller cluster sizes produced stable results, while models with larger cluster sizes, that may have had complex within-cluster correlation structures and that had within-cluster covariates, produced estimates sensitive to the correlation structure. The preferred model arising from this dataset assumed that catches from a vessel were correlated in the same years and the same areas, but independent in different years and areas. The model that assumed catches from a vessel were correlated in all years and areas, equivalent to a random effects term for vessel, produced spurious results. This was an unexpected finding that highlighted the need to adopt a systematic strategy for modelling. The article proposes a modelling strategy of selecting the best cluster definition first, and the working correlation structure (within clusters) second. The article discusses the selection and interpretation of the model in the light of background knowledge of the data and utility of the model, and the potential for this modelling approach to apply in similar statistical situations.     

Comparative Study of Generalized Estimating Equations and Logistic Regressions on Different Sample Sizes and Correlation Levels

In this study, it was aimed to determine accuracy of generalized estimating equations versus logistic regressions on different correlation levels and sample sizes. For this aim, two methods were compared with different sample sizes 10, 25, 50 and 100 and correlation levels 0.0, 0.3, 0.5 and 0.8. Result of this study showed that using generalized estimating equations could be preferred versus logistic regression when the sample size is over than 25 and correlation level is higher than 0.3 on data taken from studies with repeated measurements, but logistic regression could be better when the autocorrelations do not exist.     

A Class of Weighted Estimating Equations for Semiparametric Transformation Models with Missing Covariates

In survival analysis, covariate measurements often contain missing observations; ignoring this feature can lead to invalid inference. We propose a class of weighted estimating equations for right‐censored data with missing covariates under semiparametric transformation models. Time‐specific and subject‐specific weights are accommodated in the formulation of the weighted estimating equations. We establish unified results for estimating missingness probabilities that cover both parametric and non‐parametric modelling schemes. To improve estimation efficiency, the weighted estimating equations are augmented by a new set of unbiased estimating equations. The resultant estimator has the so‐called ‘double robustness’ property and is optimal within a class of consistent estimators.     

Efficient Estimation in Marginal Partially Linear Models for Longitudinal/Clustered Data Using Splines

Abstract.  We consider marginal semiparametric partially linear models for longitudinal/clustered data and propose an estimation procedure based on a spline approximation of the non-parametric part of the model and an extension of the parametric marginal generalized estimating equations (GEE). Our estimates of both parametric part and non-parametric part of the model have properties parallel to those of parametric GEE, that is, the estimates are efficient if the covariance structure is correctly specified and they are still consistent and asymptotically normal even if the covariance structure is misspecified. By showing that our estimate achieves the semiparametric information bound, we actually establish the efficiency of estimating the parametric part of the model in a stronger sense than what is typically considered for GEE. The semiparametric efficiency of our estimate is obtained by assuming only conditional moment restrictions instead of the strict multivariate Gaussian error assumption.     

Marginal Correlation in Longitudinal Binary Data Based on Generalized Linear Mixed Models

This work aims at investigating marginal correlation within and between longitudinal data sequences. Useful and intuitive approximate expressions are derived based on generalized linear mixed models. Data from four double-blind randomized clinical trials are used to estimate the intra-class coefficient of reliability for a binary response. Additionally, the correlation between such a binary response and a continuous response is derived to evaluate the criterion validity of the binary response variable and the established continuous response variable.     

Semiparametric Regression Analysis of Longitudinal Skewed Data

In this paper, we develop a semiparametric regression model for longitudinal skewed data. In the new model, we allow the transformation function and the baseline function to be unknown. The proposed model can provide a much broader class of models than the existing additive and multiplicative models. Our estimators for regression parameters, transformation function and baseline function are asymptotically normal. Particularly, the estimator for the transformation function converges to its true value at the rate n ^{? 1 ∕ 2}, the convergence rate that one could expect for a parametric model. In simulation studies, we demonstrate that the proposed semiparametric method is robust with little loss of efficiency. Finally, we apply the new method to a study on longitudinal health care costs.     

Regression Analysis of Longitudinal Data with Time‐Dependent Covariates and Informative Observation Times

Abstract. Longitudinal data frequently occur in many studies, and longitudinal responses may be correlated with observation times. In this paper, we propose a new joint modelling for the analysis of longitudinal data with time‐dependent covariates and possibly informative observation times via two latent variables. For inference about regression parameters, estimating equation approaches are developed and asymptotic properties of the proposed estimators are established. In addition, a lack‐of‐fit test is presented for assessing the adequacy of the model. The proposed method performs well in finite‐sample simulation studies, and an application to a bladder tumour study is provided.     

Estimators Based on Data‐Driven Generalized Weighted Cramér‐von Mises Distances under Censoring – with Applications to Mixture Models

Abstract. Estimators based on data‐driven generalized weighted Cramér‐von Mises distances are defined for data that are subject to a possible right censorship. The function used to measure the distance between the data, summarized by the Kaplan–Meier estimator, and the target model is allowed to depend on the sample size and, for example, on the number of censored items. It is shown that the estimators are consistent and asymptotically multivariate normal for every p dimensional parametric family fulfiling some mild regularity conditions. The results are applied to finite mixtures. Simulation results for finite mixtures indicate that the estimators are useful for moderate sample sizes. Furthermore, the simulation results reveal the usefulness of sample size dependent and censoring sensitive distance functions for moderate sample sizes. Moreover, the estimators for the mixing proportion seem to be fairly robust against a ‘symmetric’ contamination model even when censoring is present.     

Weighted Estimating Equations for Linear Regression Analysis of Clustered Failure Time Data

Estimation of regression parameters in linear survival models is considered in the clustered data setting. One step updates from an initial consistent estimator are proposed. The updates are based on scores that are functions of ranks of the residuals, and that incorporate weight matrices to improve efficiency. Optimal weights are approximated as the solution to a quadratic programming problem, and asymptotic relative efficiencies to various other weights computed. Except under strong dependence, simpler methods are found to be nearly as efficient as the optimal weights. The performance of several practical estimators based on exchangeable and independence working models is explored in simulations.     

An Appraisal of Methods for the Analysis of Longitudinal Ordinal Response Data with Random Dropout Using a Nonhomogeneous Markov Model

There are many methods for analyzing longitudinal ordinal response data with random dropout. These include maximum likelihood (ML), weighted estimating equations (WEEs), and multiple imputations (MI). In this article, using a Markov model where the effect of previous response on the current response is investigated as an ordinal variable, the likelihood is partitioned to simplify the use of existing software. Simulated data, generated to present a three-period longitudinal study with random dropout, are used to compare performance of ML, WEE, and MI methods in terms of standardized bias and coverage probabilities. These estimation methods are applied to a real medical data set.     

A Note on the Large Sample Properties of Estimators Based on Generalized Linear Models for Correlated Pseudo‐observations

Pseudo‐values have proven very useful in censored data analysis in complex settings such as multi‐state models. It was originally suggested by Andersen et al., Biometrika, 90, 2003, 335 who also suggested to estimate standard errors using classical generalized estimating equation results. These results were studied more formally in Graw et al., Lifetime Data Anal., 15, 2009, 241 that derived some key results based on a second‐order von Mises expansion. However, results concerning large sample properties of estimates based on regression models for pseudo‐values still seem unclear. In this paper, we study these large sample properties in the simple setting of survival probabilities and show that the estimating function can be written as a U‐statistic of second order giving rise to an additional term that does not vanish asymptotically. We further show that previously advocated standard error estimates will typically be too large, although in many practical applications the difference will be of minor importance. We show how to estimate correctly the variability of the estimator. This is further studied in some simulation studies.     

Asymptotic Properties of M-estimators Based on Estimating Equations and Censored Data

Properties of Huber's M-estimators based on estimating equations have been studied extensively and are well understood for complete (i.i.d.) data. Although the concepts of M-estimators and influence curves have been extended for some time by Reid (1981) to incomplete data that are subject to right censoring, results on the general behavior of M-estimators based on incomplete data remain scattered and restrictive. This paper establishes a general large sample theory for M-estimators based on censored data. We show how to extend any asymptotic result available for M-estimators based on complete data to the case of censored data. The extensions are usually straightforward and include the multiparameter situation. Both the lifetime and censoring distributions may be discontinuous. We illustrate several extensions which provide simple and tractable sufficient conditions for an M-estimator to be strongly consistent and asymptotically normal. The influence curves and asymptotic variance of the M-estimators are also derived. The applicability of the new sufficient conditions is demonstrated through several examples, including location and scale M-estimators.     

Bayesian Analysis of Nonlinear Reproductive Dispersion Mixed Models for Longitudinal Data with Nonignorable Missing Covariates

This article proposes a Bayesian approach, which can simultaneously obtain the Bayesian estimates of unknown parameters and random effects, to analyze nonlinear reproductive dispersion mixed models (NRDMMs) for longitudinal data with nonignorable missing covariates and responses. The logistic regression model is employed to model the missing data mechanisms for missing covariates and responses. A hybrid sampling procedure combining the Gibber sampler and the Metropolis-Hastings algorithm is presented to draw observations from the conditional distributions. Because missing data mechanism is not testable, we develop the logarithm of the pseudo-marginal likelihood, deviance information criterion, the Bayes factor, and the pseudo-Bayes factor to compare several competing missing data mechanism models in the current considered NRDMMs with nonignorable missing covaraites and responses. Three simulation studies and a real example taken from the paediatric AIDS clinical trial group ACTG are used to illustrate the proposed methodologies. Empirical results show that our proposed methods are effective in selecting missing data mechanism models.