Robust modified profile estimating function with application to the generalized estimating equation

We consider methods for reducing the effect of fitting nuisance parameters on a general estimating function, when the estimating function depends on not only a vector of parameters of interest, θ$\theta$, but also on a vector of nuisance parameters, λ$\lambda$. We propose a class of modified profile estimating functions with plug-in bias reduced by two orders. A robust version of the adjustment term does not require any information about the probability mechanism beyond that required by the original estimating function. An important application of this method is bias correction for the generalized estimating equation in analyzing stratified longitudinal data, where the stratum-specific intercepts are considered as fixed nuisance parameters, the dependence of the expected outcome on the covariates is of interest, and the intracluster correlation structure is unknown. Furthermore, when the quasi-scores for θ$\theta$ and λ$\lambda$ are available, we propose an additional multiplicative adjustment term such that the modified profile estimating function is approximately information unbiased. This multiplicative adjustment term can serve as an optimal weight in the analysis of stratified studies. A brief simulation study shows that the proposed method considerably reduces the impact of the nuisance parameters.     

Asymptotic properties of a conditional maximum-likelihood estimator

Inference for a scalar interest parameter in the presence of nuisance parameters is considered in terms of the conditional maximum-likelihood estimator developed by Cox and Reid (1987). Parameter orthogonality is assumed throughout. The estimator is analyzed by means of stochastic asymptotic expansions in three cases: a scalar nuisance parameter, m nuisance parameters from m independent samples, and a vector nuisance parameter. In each case, the expansion for the conditional maximum-likelihood estimator is compared with that for the usual maximum-likelihood estimator. The means and variances are also compared. In each of the cases, the bias of the conditional maximum-likelihood estimator is unaffected by the nuisance parameter to first order. This is not so for the maximum-likelihood estimator. The assumption of parameter orthogonality is crucial in attaining this result. Regardless of parametrization, the difference in the two estimators is first-order and is deterministic to this order.     

Sequential estimation for a family of counting processes in the nuisance parameter case

The paper deals with the problem of sequential estimation for stochastic processes in the presence of a nuisance parameter. Using the approach to estimation through estimating equations, optimum estimating functions based on a random observation time are investigated in some models for processes appearing in reliability systems theory.     

Bounded Estimation in the Presence of Nuisance Parameters

The aim of this paper is to extend in a natural fashion the results on the treatment of nuisance parameters from the profile likelihood theory to the field of robust statistics. Similarly to what happens when there are no nuisance parameters, the attempt is to derive a bounded estimating function for a parameter of interest in the presence of nuisance parameters. The proposed method is based on a classical truncation argument of the theory of robustness applied to a generalized profile score function. By means of comparative studies, we show that this robust procedure for inference in the presence of a nuisance parameter can be used successfully in a parametric setting.     

Inference about regression parameters using highly stratified survey count data with over-dispersion and repeated measurements

We study methods to estimate regression and variance parameters for over-dispersed and correlated count data from highly stratified surveys. Our application involves counts of fish catches from stratified research surveys and we propose a novel model in fisheries science to address changes in survey protocols. A challenge with this model is the large number of nuisance parameters which leads to computational issues and biased statistical inferences. We use a computationally efficient profile generalized estimating equation method and compare it to marginal maximum likelihood (MLE) and restricted MLE (REML) methods. We use REML to address bias and inaccurate confidence intervals because of many nuisance parameters. The marginal MLE and REML approaches involve intractable integrals and we used a new R package that is designed for estimating complex nonlinear models that may include random effects. We conclude from simulation analyses that the REML method provides more reliable statistical inferences among the three methods we investigated.     

A simple approach to analyzing clustered longitudinal data

When modeling correlated binary data in the presence of informative cluster sizes, generalized estimating equations with either resampling or inverse-weighting, are often used to correct for estimation bias. However, existing methods for the clustered longitudinal setting assume constant cluster sizes over time. We present a subject-weighted generalized estimating equations scheme that provides valid parameter estimation for the clustered longitudinal setting while allowing cluster sizes to change over time. We compare, via simulation, the performance of existing methods to our subject-weighted approach. The subject-weighted approach was the only method that showed negligible bias, with excellent coverage, for all model parameters.     

Estimated estimating equations: semiparametric inference for clustered and longitudinal data

Summary.  We introduce a flexible marginal modelling approach for statistical inference for clustered and longitudinal data under minimal assumptions. This estimated estimating equations approach is semiparametric and the proposed models are fitted by quasi-likelihood regression, where the unknown marginal means are a function of the fixed effects linear predictor with unknown smooth link, and variance–covariance is an unknown smooth function of the marginal means. We propose to estimate the nonparametric link and variance–covariance functions via smoothing methods, whereas the regression parameters are obtained via the estimated estimating equations. These are score equations that contain nonparametric function estimates. The proposed estimated estimating equations approach is motivated by its flexibility and easy implementation. Moreover, if data follow a generalized linear mixed model, with either a specified or an unspecified distribution of random effects and link function, the model proposed emerges as the corresponding marginal (population-average) version and can be used to obtain inference for the fixed effects in the underlying generalized linear mixed model, without the need to specify any other components of this generalized linear mixed model. Among marginal models, the estimated estimating equations approach provides a flexible alternative to modelling with generalized estimating equations. Applications of estimated estimating equations include diagnostics and link selection. The asymptotic distribution of the proposed estimators for the model parameters is derived, enabling statistical inference. Practical illustrations include Poisson modelling of repeated epileptic seizure counts and simulations for clustered binomial responses.     

Variance function in regression analysis of longitudinal data using the generalized estimating equation approach

Longitudinal or clustered response data arise in many applications such as biostatistics, epidemiology and environmental studies. The repeated responses cannot in general be assumed to be independent. One method of analysing such data is by using the generalized estimating equations (GEE) approach. The current GEE method for estimating regression effects in longitudinal data focuses on the modelling of the working correlation matrix assuming a known variance function. However, correct choice of the correlation structure may not necessarily improve estimation efficiency for the regression parameters if the variance function is misspecified [Wang YG, Lin X. Effects of variance-function misspecification in analysis of longitudinal data. Biometrics. 2005;61:413–421]. In this connection two problems arise: finding a correct variance function and estimating the parameters of the chosen variance function. In this paper, we study the problem of estimating the parameters of the variance function assuming that the form of the variance function is known and then the effect of a misspecified variance function on the estimates of the regression parameters. We propose a GEE approach to estimate the parameters of the variance function. This estimation approach borrows the idea of Davidian and Carroll [Variance function estimation. J Amer Statist Assoc. 1987;82:1079–1091] by solving a nonlinear regression problem where residuals are regarded as the responses and the variance function is regarded as the regression function. A limited simulation study shows that the proposed method performs at least as well as the modified pseudo-likelihood approach developed by Wang and Zhao [A modified pseudolikelihood approach for analysis of longitudinal data. Biometrics. 2007;63:681–689]. Both these methods perform better than the GEE approach.     

Mimicking Cox-Regression

Abstract

A class of objective functions, related to the Cox partial likelihood, that generates unbiased estimating equations is proposed. These equations allow for estimation of interest parameters when nuisance parameters are proportional to expectations. Examples of the objective functions are applied to binary data with a log-link in three situations: independent observations, independent groups of observations with common random intercept and discrete survival data. It is pointed out that the Peto–Breslow approximation to the partial likelihood with discrete failure times fits a conditional model with a log-link.     

Modified quasi-profile likelihoods from estimating functions

We discuss higher-order adjustments for a quasi-profile likelihood for a scalar parameter of interest, in order to alleviate some of the problems inherent to the presence of nuisance parameters, such as bias and inconsistency. Indeed, quasi-profile score functions for the parameter of interest have bias of order O(1)$\mathrm{O}(1)$, and such bias can lead to poor inference on the parameter of interest. The higher-order adjustments are obtained so that the adjusted quasi-profile score estimating function is unbiased and its variance is the negative expected derivative matrix of the adjusted profile estimating equation. The modified quasi-profile likelihood is then obtained as the integral of the adjusted profile estimating function. We discuss two methods for the computation of the modified quasi-profile likelihoods: a bootstrap simulation method and a first-order asymptotic expression, which can be simplified under an orthogonality assumption. Examples in the context of generalized linear models and of robust inference are provided, showing that the use of a modified quasi-profile likelihood ratio statistic may lead to coverage probabilities more accurate than those pertaining to first-order Wald-type confidence intervals.     

Estimating generalized semiparametric additive models using parameter cascading

Elimination of nuisance parameters is a central but difficult problem in statistical inference. We propose the parameter cascading method to estimate statistical models that involve nuisance parameters, structural parameters, and complexity parameters. The parameter cascading method has several unique aspects. First, we consider functional relationships between parameters, quantitatively described using analytical derivatives. These functional relationships can be explicit or implicit, and in the latter case the Implicit Function Theorem is applied to obtain the required derivatives. Second, we can express the gradients and Hessian matrices analytically, which is essential for fast and stable computation. Third, we develop the unconditional variance estimates for parameters, which include the uncertainty coming from other parameter estimates. The parameter cascading method is demonstrated by estimating generalized semiparametric additive models (GSAMs), where the response variable is allowed to be from any distribution. The practical necessity and empirical performance of the parameter cascading method are illustrated through a simulation study, and two applied example, one on finding the effect of air pollution on public health, and the other on the management of a retirement fund. The results demonstrate that the parameter cascading method is a good alternative to traditional methods.     

Semiparametric Estimation in Copulas with the Same Marginals

We consider semiparametric multivariate data models based on copula representation of the common distribution function. A copula is characterized by a parameter of association and marginal distribution functions. This parameter and the marginal distributions are unknown. In this article, we study the estimator of the parameter of association in copulas with the marginal distribution functions assumed as nuisance parameters restricted by the assumption that the components are identically distributed. Results of this work could be used to construct special kinds of tests of homogeneity for random vectors having dependent components.     

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.     

Targeted estimation of state occupation probabilities for the non-Markov illness-death model

We use semi-parametric efficiency theory to derive a class of estimators for the state occupation probabilities of the continuous-time irreversible illness-death model. We consider both the setting with and without additional baseline information available, where we impose no specific functional form on the intensity functions of the model. We show that any estimator in the class is asymptotically linear under suitable assumptions about the estimators of the intensity functions. In particular, the assumptions are weak enough to allow the use of data-adaptive methods, which is important for making the identifying assumption of coarsening at random plausible in realistic settings. We suggest a flexible method for estimating the transition intensity functions of the illness-death model based on penalized Poisson regression. We apply this method to estimate the nuisance parameters of an illness-death model in a simulation study and a real-world application.     

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.     

A Comparison of Correlation Structure Selection Penalties for Generalized Estimating Equations

Correlated data are commonly analyzed using models constructed using population-averaged generalized estimating equations (GEEs). The specification of a population-averaged GEE model includes selection of a structure describing the correlation of repeated measures. Accurate specification of this structure can improve efficiency, whereas the finite-sample estimation of nuisance correlation parameters can inflate the variances of regression parameter estimates. Therefore, correlation structure selection criteria should penalize, or account for, correlation parameter estimation. In this article, we compare recently proposed penalties in terms of their impacts on correlation structure selection and regression parameter estimation, and give practical considerations for data analysts. Supplementary materials for this article are available online.     

Efficient estimation in partially linear single‐index models for longitudinal data

In this paper, we consider the estimation of both the parameters and the nonparametric link function in partially linear single‐index models for longitudinal data that may be unbalanced. In particular, a new three‐stage approach is proposed to estimate the nonparametric link function using marginal kernel regression and the parametric components with generalized estimating equations. The resulting estimators properly account for the within‐subject correlation. We show that the parameter estimators are asymptotically semiparametrically efficient. We also show that the asymptotic variance of the link function estimator is minimized when the working error covariance matrices are correctly specified. The new estimators are more efficient than estimators in the existing literature. These asymptotic results are obtained without assuming normality. The finite‐sample performance of the proposed method is demonstrated by simulation studies. In addition, two real‐data examples are analyzed to illustrate the methodology.     

A robust approach to longitudinal data analysis

The author introduces robust techniques for estimation, inference and variable selection in the analysis of longitudinal data. She first addresses the problem of the robust estimation of the regression and nuisance parameters, for which she derives the asymptotic distribution. She uses weighted estimating equations to build robust quasi‐likelihood functions. These functions are then used to construct a class of test statistics for variable selection. She derives the limiting distribution of these tests and shows its robustness properties in terms of stability of the asymptotic level and power under contamination. An application to a real data set allows her to illustrate the benefits of a robust analysis.     

ASYMPTOTIC DISTRIBUTIONS OF SEMIPARAMETRIC MAXIMUM LIKELIHOOD ESTIMATORS WITH ESTIMATING EQUATIONS FOR GROUP-CENSORED DATA

Semiparametric maximum likelihood estimation with estimating equations (SMLE) is more flexible than traditional methods; it has fewer restrictions on distributions and regression models. The required information about distribution and regression structures is incorporated in estimating equations of the SMLE to improve the estimation quality of non‐parametric methods. The likelihood of SMLE for censored data involves complicated implicit functions without closed‐form expressions, and the first derivatives of the log‐profile‐likelihood cannot be expressed as summations of independent and identically distributed random variables; it is challenging to derive asymptotic properties of the SMLE for censored data. For group‐censored data, the paper shows that all the implicit functions are well defined and obtains the asymptotic distributions of the SMLE for model parameters and lifetime distributions. With several examples the paper compares the SMLE, the regular non‐parametric likelihood estimation method and the parametric MLEs in terms of their asymptotic efficiencies, and illustrates application of SMLE. Various asymptotic distributions of the likelihood ratio statistics are derived for testing the adequacy of estimating equations and a partial set of parameters equal to some known values.     

On comparing two methods for approximate conditional inference

Approximate conditional inference for a real parameter in the presence of nuisance parameters was examined from a sample-space differential viewpoint in Fraser and Reid (1988) and a conditional inference procedure was proposed. Conditional likelihood-based inference in the same setting was discussed in Cox and Reid (1987), where emphasis was placed on orthogonalizing the nuisance parameter to the parameter of interest. In this paper the sample-space partitions of the two methods are examined for the case that the minimal sufficient statistic has the same dimension as the parameter space. The methods are identical if observed and expected information gives the same orthogonality; an example indicates how they can differ more generally. A specially chosen reparameterization provides some geometrical insight to the methods and allows a comparison in terms of score functions and locally defined orthogonal parameters.