A Pairwise Likelihood Procedure for Analyzing Exchangeable Binary Data with Random Cluster Sizes

For the exchangeable binary data with random cluster sizes, we use a pairwise likelihood procedure to give a set of approximately optimal unbiased estimating equations for estimating the mean and variance parameters. Theoretical results are obtained establishing the large sample properties of the solutions to the estimating equations. An application to a developmental toxicity study is given. Simulation results show that the pairwise likelihood procedure is valid and performs better than the GEE procedure for the exchangeable binary data.     

Expected estimating equations to accommodate covariate measurement error

Estimating equations which are not necessarily likelihood-based score equations are becoming increasingly popular for estimating regression model parameters. This paper is concerned with estimation based on general estimating equations when true covariate data are missing for all the study subjects, but surrogate or mismeasured covariates are available instead. The method is motivated by the covariate measurement error problem in marginal or partly conditional regression of longitudinal data. We propose to base estimation on the expectation of the complete data estimating equation conditioned on available data. The regression parameters and other nuisance parameters are estimated simultaneously by solving the resulting estimating equations. The expected estimating equation (EEE) estimator is equal to the maximum likelihood estimator if the complete data scores are likelihood scores and conditioning is with respect to all the available data. A pseudo-EEE estimator, which requires less computation, is also investigated. Asymptotic distribution theory is derived. Small sample simulations are conducted when the error process is an order 1 autoregressive model. Regression calibration is extended to this setting and compared with the EEE approach. We demonstrate the methods on data from a longitudinal study of the relationship between childhood growth and adult obesity.     

Jackknife Empirical Likelihood for the Accelerated Failure Time Model with Censored Data

Kendall and Gehan estimating functions are commonly used to estimate the regression parameter in accelerated failure time model with censored observations in survival analysis. In this paper, we apply the jackknife empirical likelihood method to overcome the computation difficulty about interval estimation. A Wilks’ theorem of jackknife empirical likelihood for U-statistic type estimating equations is established, which is used to construct the confidence intervals for the regression parameter. We carry out an extensive simulation study to compare the Wald-type procedure, the empirical likelihood method, and the jackknife empirical likelihood method. The proposed jackknife empirical likelihood method has a better performance than the existing methods. We also use a real data set to compare the proposed methods.     

Orthogonalized Residuals for Estimation of Marginally Specified Association Parameters in Multivariate Binary Data

Abstract. This paper focuses on marginal regression models for correlated binary responses when estimation of the association structure is of primary interest. A new estimating function approach based on orthogonalized residuals is proposed. A special case of the proposed procedure allows a new representation of the alternating logistic regressions method through marginal residuals. The connections between second‐order generalized estimating equations, alternating logistic regressions, pseudo‐likelihood and other methods are explored. Efficiency comparisons are presented, with emphasis on variable cluster size and on the role of higher‐order assumptions. The new method is illustrated with an analysis of data on impaired pulmonary function.     

Generalized additive models for longitudinal data

We introduce a class of models for longitudinal data by extending the generalized estimating equations approach of Liang and Zeger (1986) to incorporate the flexibility of nonparametric smoothing. The algorithm provides a unified estimation procedure for marginal distributions from the exponential family. We propose pointwise standard-error bands and approximate likelihood-ratio and score tests for inference. The algorithm is formally derived by using the penalized quasilikelihood framework. Convergence of the estimating equations and consistency of the resulting solutions are discussed. We illustrate the algorithm with data on the population dynamics of Colorado potato beetles on potato plants.     

Estimation of conditional cumulative incidence functions under generalized semiparametric regression models with missing covariates,with application to analysis of biomarker correlates in vaccine trials

This article presents generalized semiparametric regression models for conditional cumulative incidence functions with competing risks data when covariates are missing by sampling design or happenstance. A doubly robust augmented inverse probability weighted (AIPW) complete-case approach to estimation and inference is investigated. This approach modifies IPW complete-case estimating equations by exploiting the key features in the relationship between the missing covariates and the phase-one data to improve efficiency. An iterative numerical procedure is derived to solve the nonlinear estimating equations. The asymptotic properties of the proposed estimators are established. A simulation study examining the finite-sample performances of the proposed estimators shows that the AIPW estimators are more efficient than the IPW estimators. The developed method is applied to the RV144 HIV-1 vaccine efficacy trial to investigate vaccine-induced IgG binding antibodies to HIV-1 as correlates of acquisition of HIV-1 infection while taking account of whether the HIV-1 sequences are near or far from the HIV-1 sequences represented in the vaccine construct.     

A working estimating equation for spatial count data

This paper proposes a working estimating equation which is computationally easy to use for spatial count data. The proposed estimating equation is a modification of quasi-likelihood estimating equations without the need of correctly specifying the covariance matrix. Under some regularity conditions, we show that the proposed estimator has consistency and asymptotic normality. A simulation comparison also indicates that the proposed method has competitive performance in dealing with over-dispersion data from a parameter-driven model.     

Partially linear transformation model for length-biased and right-censored data

In this paper, we consider a partially linear transformation model for data subject to length-biasedness and right-censoring which frequently arise simultaneously in biometrics and other fields. The partially linear transformation model can account for nonlinear covariate effects in addition to linear effects on survival time, and thus reconciles a major disadvantage of the popular semiparamnetric linear transformation model. We adopt local linear fitting technique and develop an unbiased global and local estimating equations approach for the estimation of unknown covariate effects. We provide an asymptotic justification for the proposed procedure, and develop an iterative computational algorithm for its practical implementation, and a bootstrap resampling procedure for estimating the standard errors of the estimator. A simulation study shows that the proposed method performs well in finite samples, and the proposed estimator is applied to analyse the Oscar data.     

A semiparametric extended hazard regression model with time-dependent covariates

We introduce a general class of semiparametric hazard regression models, called extended hazard (EH) models, that are designed to accommodate various survival schemes with time-dependent covariates. The EH model contains both the Cox model and the accelerated failure time (AFT) model as its subclasses so that we can use this nested structure to perform model selection between the Cox model and the AFT model. A class of estimating equations using counting process and martingale techniques is developed to estimate the regression parameters of the proposed model. The performance of the estimating procedure and the impact of model misspecification are assessed through simulation studies. Two data examples, Stanford heart transplant data and Mediterranean fruit flies, egg-laying data, are used to demonstrate the usefulness of the EH model.     

Quickly variable selection for varying coefficient models with missing response at random

This paper focuses on the variable selections for a varying coefficient models with missing response at random. A procedure is presented by basis function approximations with smooth-threshold estimating equations. Furthermore, the proposed method selects significant variables and estimates coefficients simultaneously avoiding the problem of solving a convex optimization, which reduced the burden of computation. Compared to existing equation based approaches, our procedure is more efficient and quick. With proper choices the regularization parameter, the resulting estimates perform an oracle property. A cross-validation for tuning parameter selection is also proposed, a numerical study confirms the performance of the proposed method.     

Estimating and testing group effects from type i censored normal samples in experimental design

The maximum likelihood (ML) equations calculated from censored normal samples do not admit explicit solutions. A principle of modification is given and modified maximum likelihood (MML) equations, which admit explicit solutions, are defined. This approach makes it possible to tackle the hitherto unresolved problem of estimating and testing hypotheses about group-effects in one-way classification experimental designs based on Type I censored normal samples. The MML estimators of group-effects are obtained as explicit functions of sample observations and shown to be asymptotically identical with the ML estimators and hence BAN (best asymptotic normal) estimators. A statistic t is defined to test a linear contrast of group-effects and shown to be asymptotically normally distributed. A numerical example is presented which illustrates the procedure.     

A Comparison of Utilized and Theoretical Covariance Weighting Matrices on the Estimation Performance of Quadratic Inference Functions

The quadratic inference function (QIF) method is increasingly popular for the marginal analysis of correlated data due to its advantages over generalized estimating equations. Asymptotic theory is used to derive analytical results from the QIF, and we, therefore, study three asymptotically equivalent weighting matrices in terms of finite-sample parameter estimation. Furthermore, to improve small-sample estimation, we study modifications to the estimation procedure. Examples are presented via simulations and application. Results show that although theoretical weighting matrices work best, the proposed estimation procedure, in which initial estimates are held constant within the matrix of estimated empirical covariances, is preferable in practice.     

Dimension reduction in estimating equations with covariates missing at random

To estimate parameters defined by estimating equations with covariates missing at random, we consider three bias-corrected nonparametric approaches based on inverse probability weighting, regression and augmented inverse probability weighting. However, when the dimension of covariates is not low, the estimation efficiency will be affected due to the curse of dimensionality. To address this issue, we propose a two-stage estimation procedure by using the dimension-reduced kernel estimation in conjunction with bias-corrected estimating equations. We show that the resulting three estimators are asymptotically equivalent and achieve the desirable properties. The impact of dimension reduction in nonparametric estimation of parameters is also investigated. The finite-sample performance of the proposed estimators is studied through simulation, and an application to an automobile data set is also presented.     

Modified SEE variable selection for varying coefficient instrumental variable models

We consider the problem of variable selection for a class of varying coefficient models with instrumental variables. We focus on the case that some covariates are endogenous variables, and some auxiliary instrumental variables are available. An instrumental variable based variable selection procedure is proposed by using modified smooth-threshold estimating equations (SEEs). The proposed procedure can automatically eliminate the irrelevant covariates by setting the corresponding coefficient functions as zero, and simultaneously estimate the nonzero regression coefficients by solving the smooth-threshold estimating equations. The proposed variable selection procedure avoids the convex optimization problem, and is flexible and easy to implement. Simulation studies are carried out to assess the performance of the proposed variable selection method.     

Variable selection for longitudinal data with high-dimensional covariates and dropouts

A new variable selection approach utilizing penalized estimating equations is developed for high-dimensional longitudinal data with dropouts under a missing at random (MAR) mechanism. The proposed method is based on the best linear approximation of efficient scores from the full dataset and does not need to specify a separate model for the missing or imputation process. The coordinate descent algorithm is adopted to implement the proposed method and is computational feasible and stable. The oracle property is established and extensive simulation studies show that the performance of the proposed variable selection method is much better than that of penalized estimating equations dealing with complete data which do not account for the MAR mechanism. In the end, the proposed method is applied to a Lifestyle Education for Activity and Nutrition study and the interaction effect between intervention and time is identified, which is consistent with previous findings.     

Estimation in an empirical bayes model for longitudinal and cross‐sectionally clustered binary data

Some studies generate data that can be grouped into clusters in more than one way. Consider for instance a smoking prevention study in which responses on smoking status are collected over several years in a cohort of students from a number of different schools. This yields longitudinal data, also cross‐sectionaliy clustered in schools. The authors present a model for analyzing binary data of this type, combining generalized estimating equations and estimation of random effects to address the longitudinal and cross‐sectional dependence, respectively. The estimation procedure for this model is discussed, as are the results of a simulation study used to investigate the properties of its estimates. An illustration using data from a smoking prevention trial is given.     

ROBUST NON-PARAMETRIC ESTIMATION OF GENOTYPE–PHENOTYPE RELATIONSHIPS IN HUMAN PEDIGREES

Non‐parametric estimation of functional relationships is an important part of data analysis, particularly in the exploratory stages. This paper considers non‐parametric estimation of the mean functions in family studies using weighted robust estimating equations while retaining a fully parametric model for the covariance structure. The proposed procedure allows an exploratory examination of complex pedigree data that is an invaluable aid in determining appropriate models. This is illustrated by an examination of the relationship between IQ and the level of a particular protein in individuals collected as part of a large family study.     

Building adaptive estimating equations when inverse of covariance estimation is difficult

Summary. To construct an optimal estimating function by weighting a set of score functions, we must either know or estimate consistently the covariance matrix for the individual scores. In problems with high dimensional correlated data the estimated covariance matrix could be unreliable. The smallest eigenvalues of the covariance matrix will be the most important for weighting the estimating equations, but in high dimensions these will be poorly determined. Generalized estimating equations introduced the idea of a working correlation to minimize such problems. However, it can be difficult to specify the working correlation model correctly. We develop an adaptive estimating equation method which requires no working correlation assumptions. This methodology relies on finding a reliable approximation to the inverse of the variance matrix in the quasi-likelihood equations. We apply a multivariate generalization of the conjugate gradient method to find estimating equations that preserve the information well at fixed low dimensions. This approach is particularly useful when the estimator of the covariance matrix is singular or close to singular, or impossible to invert owing to its large size.     

Pseudo-observations for competing risks with covariate dependent censoring

Regression analysis for competing risks data can be based on generalized estimating equations. For the case with right censored data, pseudo-values were proposed to solve the estimating equations. In this article we investigate robustness of the pseudo-values against violation of the assumption that the probability of not being lost to follow-up (un-censored) is independent of the covariates. Modified pseudo-values are proposed which rely on a correctly specified regression model for the censoring times. Bias and efficiency of these methods are compared in a simulation study. Further illustration of the differences is obtained in an application to bone marrow transplantation data and a corresponding sensitivity analysis.     

Estimation of a two-equation panel model with mixed continuous and ordered categorical outcomes and missing data

Summary.  The paper proposes an estimation approach for panel models with mixed continuous and ordered categorical outcomes based on generalized estimating equations for the mean and pseudoscore equations for the covariance parameters. A numerical study suggests that efficiency can be gained in the mean parameter estimators by using individual covariance matrices in the estimating equations for the mean parameters. The approach is applied to estimate the returns to occupational qualification in terms of income and perceived job security in a 9-year period based on the German Socio-Economic Panel. To compensate for missing data, a combined multiple imputation–weighting approach is adopted.