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.     

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.     

A PRESS statistic for working correlation structure selection in generalized estimating equations

Generalized estimating equations (GEE) is one of the most commonly used methods for regression analysis of longitudinal data, especially with discrete outcomes. The GEE method accounts for the association among the responses of a subject through a working correlation matrix and its correct specification ensures efficient estimation of the regression parameters in the marginal mean regression model. This study proposes a predicted residual sum of squares (PRESS) statistic as a working correlation selection criterion in GEE. A simulation study is designed to assess the performance of the proposed GEE PRESS criterion and to compare its performance with its counterpart criteria in the literature. The results show that the GEE PRESS criterion has better performance than the weighted error sum of squares SC criterion in all cases but is surpassed in performance by the Gaussian pseudo-likelihood criterion. Lastly, the working correlation selection criteria are illustrated with data from the Coronary Artery Risk Development in Young Adults study.     

固定效应部分线性变系数面板模型的快速有效估计

本文将最小二乘支持向量机(LSSVM) 和二次推断函数法(QIF) 相结合，为个体内具有相关结构的固定效应部分线性变系数面板模型提供了一种新的快速估计方法；在一定的正则条件下，论证了参数估计量的渐近正态性和非参数估计量的收敛速度；采用Monte Carlo模拟考察了估计方法在有限样本下的表现并将估计技术应用于现实数据分析。该方法不仅保证了估计的有效性和统计推断力，而且程序运行速度得到较大幅度提升。     

The performances of several modified CIC criteria for working intra-cluster correlation structure selection in GEE analysis

Based on various improved robust covariance estimators in the literature, several modified versions of the well-known correlated information criterion (CIC) for working intra-cluster correlation structure (ICS) selection are proposed. Performances of these modified criteria are examined and compared to the CIC via simulations. When the response is Gaussian, binary, or Poisson, the modified criteria are demonstrated to have higher detection rates when the true ICS is exchangeable, while the CIC would perform better when the true ICS is AR(1). An application of the criteria is made to a real dataset.     

Conditional mix-GEE models for longitudinal data with unspecified random-effects distributions

In the longitudinal studies, the mixture generalized estimation equation (mix-GEE) was proposed to improve the efficiency of the fixed-effects estimator for addressing the working correlation structure misspecification. When the subject-specific effect is one of interests, mixed-effects models were widely used to analyze longitudinal data. However, most of the existing approaches assume a normal distribution for the random effects, and this could affect the efficiency of the fixed-effects estimator. In this article, a conditional mixture generalized estimating equation (cmix-GEE) approach based on the advantage of mix-GEE and conditional quadratic inference function (CQIF) method is developed. The advantage of our new approach is that it does not require the normality assumption for random effects and can accommodate the serial correlation between observations within the same cluster. The feature of our proposed approach is that the estimators of the regression parameters are more efficient than CQIF even if the working correlation structure is not correctly specified. In addition, according to the estimates of some mixture proportions, the true working correlation matrix can be identified. We establish the asymptotic results for the fixed-effects parameter estimators. Simulation studies were conducted to evaluate our proposed method.     

Some Properties of the Liang-Zeger Method Applied to Clustered Binary Regression

The Generalized Estimating Equation (GEE) method popularized by Liang and Zeger provides a very general method for fitting regression models to observations that occur in clusters. Features of the method are the specification of a 'working correlation' (a guess at the true correlation structure of the data) which is used to improve efficiency in estimating the regression coefficients, and the 'information sandwich' which provides a way of consistently estimating the standard errors of the estimated regression coefficients even if (as we might expect) the working correlation is wrong. This paper develops asymptotic expressions for the bias and efficiency both of the regression coefficient estimates and of the sandwich estimate, and uses them to study the behaviour of the estimates.
It looks at the effect of the choice of the working correlation on the estimate and also examines the effect of different cluster sizes and different degrees of correlation between the covariates. The performance of these methods is found to be excellent, particularly when the degree of correlation in the responses and covariates is small to moderate.     

Variable selection in generalized estimating equations via empirical likelihood and Gaussian pseudo-likelihood

AIC and BIC based on either empirical likelihood (EAIC and EBIC) or Gaussian pseudo-likelihood (GAIC and GBIC) are proposed to select variables in longitudinal data analysis. Their performances are evaluated in the framework of the generalized estimating equations via intensive simulation studies. Our findings are: (i) GAIC and GBIC outperform other existing methods in selecting variables; (ii) EAIC and EBIC are effective in selecting covariates only when the working correlation structure is correctly specified; (iii) GAIC and GBIC perform well regardless the working correlation structure is correctly specified or not. A real dataset is also provided to illustrate the findings.     

P-value adjustment for multiple binary endpoints

The p-value-based adjustment of individual endpoints and the global test for an overall inference are the two general approaches for the analysis of multiple endpoints. Statistical procedures developed for testing multivariate outcomes often assume that the multivariate endpoints are either independent or normally distributed. This paper presents a general approach for the analysis of multivariate binary data under the framework of generalized linear models. The generalized estimating equations (GEE) approach is applied to estimate the correlation matrix of the test statistics using the identity and exchangeable working correlation matrices with the model-based as well as robust estimators. The objectives of the approaches are the adjustment of p-values of individual endpoints to identify the affected endpoints as well as the global test of an overall effect. A Monte Carlo simulation was conducted to evaluate the overall family wise error (FWE) rates of the single-step down p-value adjustment approach from two adjustment methods to three global test statistics. The p-value adjustment approach seems to control the FWE better than the global approach Applications of the proposed methods are illustrated by analyzing a carcinogenicity experiment designed to study the dose response trend for 10 tumor sites, and a developmental toxicity experiment with three malformation types: external, visceral, and skeletal.     

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.     

Consistent model selection and data-driven smooth tests for longitudinal data in the estimating equations approach

Summary.  Model selection for marginal regression analysis of longitudinal data is challenging owing to the presence of correlation and the difficulty of specifying the full likelihood, particularly for correlated categorical data. The paper introduces a novel Bayesian information criterion type model selection procedure based on the quadratic inference function, which does not require the full likelihood or quasi-likelihood. With probability approaching 1, the criterion selects the most parsimonious correct model. Although a working correlation matrix is assumed, there is no need to estimate the nuisance parameters in the working correlation matrix; moreover, the model selection procedure is robust against the misspecification of the working correlation matrix. The criterion proposed can also be used to construct a data-driven Neyman smooth test for checking the goodness of fit of a postulated model. This test is especially useful and often yields much higher power in situations where the classical directional test behaves poorly. The finite sample performance of the model selection and model checking procedures is demonstrated through Monte Carlo studies and analysis of a clinical trial data set.     

Power and sample size for GEE analysis of incomplete paired outcomes in 2 × 2 crossover trials

The 2 × 2 crossover trial uses subjects as their own control to reduce the intersubject variability in the treatment comparison, and typically requires fewer subjects than a parallel design. The generalized estimating equations (GEE) methodology has been commonly used to analyze incomplete discrete outcomes from crossover trials. We propose a unified approach to the power and sample size determination for the Wald Z-test and t-test from GEE analysis of paired binary, ordinal and count outcomes in crossover trials. The proposed method allows misspecification of the variance and correlation of the outcomes, missing outcomes, and adjustment for the period effect. We demonstrate that misspecification of the working variance and correlation functions leads to no or minimal efficiency loss in GEE analysis of paired outcomes. In general, GEE requires the assumption of missing completely at random. For bivariate binary outcomes, we show by simulation that the GEE estimate is asymptotically unbiased or only minimally biased, and the proposed sample size method is suitable under missing at random (MAR) if the working correlation is correctly specified. The performance of the proposed method is illustrated with several numerical examples. Adaption of the method to other paired outcomes is discussed.     

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.     

Parametric Analysis for Matched Pair Survival Data

Hougaard's (1986) bivariate Weibull distribution with positive stable frailties is applied to matched pairs survival data when either or both components of the pair may be censored and covariate vectors may be of arbitrary fixed length. When there is no censoring, we quantify the corresponding gain in Fisher information over a fixed-effects analysis. With the appropriate parameterization, the results take a simple algebraic form. An alternative marginal (independence working model) approach to estimation is also considered. This method ignores the correlation between the two survival times in the derivation of the estimator, but provides a valid estimate of standard error. It is shown that when both the correlation between the two survival times is high, and the ratio of the within-pair variability to the between-pair variability of the covariates is high, the fixed-effects analysis captures most of the information about the regression coefficient but the independence working model does badly. When the correlation is low, and/or most of the variability of the covariates occurs between pairs, the reverse is true. The random effects model is applied to data on skin grafts, and on loss of visual acuity among diabetics. In conclusion some extensions of the methods are indicated and they are placed in a wider context of Generalized Estimating Equation methodology.     

Pseudo-Likelihood Methodology for Hierarchical Count Data

Generalized Estimating Equations (GEE) are a widespread tool for modeling correlated data, based on properly formulating a marginal regression function, combined with working assumptions about the correlation function. Should interest be placed in addition on the correlation function, then, apart from second-order GEE, pseudo-likelihood (PL) also provides an attractive alternative, especially in its pairwise form, where the covariance between each pair of the response vector is modeled as well. An elegant PL approach is formulated in this paper, based on a flexible bivariate Poisson model. The performance of the PL-method is studied, relative to GEE, using simulations. Data on repeated counts of epileptic seizures in a two-arm clinical trial are analyzed. A macro has been developed by the authors and made available on their web pages.     

Effect of neglected deterministic seasonality on unit root tests

Whenever deterministic seasonality is ignored, the distribution of the Dickey-Fuller test is shifted to the left, with lower dispersion at the same time. When accounting for serial correlation, the distortions become less predictable. A Monte Carlo study confirms that the (augmented) Dickey-Fuller test without seasonal dummies is oversized and has little power at the same time, due to the need of lag augmentation. The effect of neglecting seasonal deterministics on the KPSS test for stationarity depends on the way the long-run variance is estimated. This is a shorter version of a working paper containing additional experimental evidence and the proofs of the propositions. The working paper is available online under http://www.wiwi.uni-frankfurt.de/~deme/ends_urt.pdf.     

系统性风险度量CoES的建模和检验

本文结合极值理论(Extreme Value Theory,EVT)和新的动态混合Copula(Dynamic Mixture Copula,DM-Copula)函数,提出了一种新的CoES估计方法DM-Copula-EVT。在EVT建模中,本文改进了阈值的选取方法以避免选择的主观性,并提出了一系列新的动态混合Copula以更好地刻画金融市场日益复杂的尾部关联性。此外,本文首次提出了检验CoES模型设定正确性的后验分析方法,包括无条件覆盖性检验和条件覆盖性检验。将本文建模和检验方法应用于我国金融市场,研究发现:相对于传统使用的t分布,EVT能更好地拟合指数的尾部分布;新的动态混合Copula函数能更好地刻画金融部门与系统之间的复杂关联性。     

Self-selection and direct estimation of across-regime correlation parameter

A direct maximum likelihood (ML) procedure to estimate the ‘generally unidentified’ across-regime correlation parameter in a two-regime endogenous switching model is here provided. The results of a Monte Carlo experiment confirm consistency of our direct ML procedure, and its relative efficiency over widely applied models and methods. As an empirical application, we estimate a two-regime simultaneous equation model of domestic work of Italian married women in which the two regimes are given by their working status (employed or unemployed).