A pseudo likelihood approach to analyze rate difference of binary response data in longitudinal factorial studies

Although Fan showed that the mixed-effects model for repeated measures (MMRM) is appropriate to analyze complete longitudinal binary data in terms of the rate difference, they focused on using the generalized estimating equations (GEE) to make statistical inference. The current article emphasizes validity of the MMRM when the normal-distribution-based pseudo likelihood approach is used to make inference for complete longitudinal binary data. For incomplete longitudinal binary data with missing at random missing mechanism, however, the MMRM, using either the GEE or the normal-distribution-based pseudo likelihood inferential procedure, gives biased results in general and should not be used for analysis.     

Regression models for analyzing clustered binary and continuous outcomes under an assumption of exchangeability

Scientific experiments commonly result in clustered discrete and continuous data. Existing methods for analyzing such data include the use of quasi-likelihood procedures and generalized estimating equations to estimate marginal mean response parameters. In applications to areas such as developmental toxicity studies, where discrete and continuous measurements are recorded on each fetus, or clinical ophthalmologic trials, where different types of observations are made on each eye, the assumption that data within cluster are exchangeable is often very reasonable. We use this assumption to formulate fully parametric regression models for clusters of bivariate data with binary and continuous components. The regression models proposed have marginal interpretations and reproducible model structures. Tractable expressions for likelihood equations are derived and iterative schemes are given for computing efficient estimates (MLEs) of the marginal mean, correlations, variances and higher moments. We demonstrate the use the ‘exchangeable’ procedure with an application to a developmental toxicity study involving fetal weight and malformation data.     

Composite conditional likelihood for sparse clustered data

Summary.  Sparse clustered data arise in finely stratified genetic and epidemiologic studies and pose at least two challenges to inference. First, it is difficult to model and interpret the full joint probability of dependent discrete data, which limits the utility of full likelihood methods. Second, standard methods for clustered data, such as pairwise likelihood and the generalized estimating function approach, are unsuitable when the data are sparse owing to the presence of many nuisance parameters. We present a composite conditional likelihood for use with sparse clustered data that provides valid inferences about covariate effects on both the marginal response probabilities and the intracluster pairwise association. Our primary focus is on sparse clustered binary data, in which case the method proposed utilizes doubly discordant quadruplets drawn from each stratum to conduct inference about the intracluster pairwise odds ratios.     

Efficiency of generalized estimating equations for binary responses

Summary.  Using standard correlation bounds, we show that in generalized estimation equations (GEEs) the so-called 'working correlation matrix' R ( α ) for analysing binary data cannot in general be the true correlation matrix of the data. Methods for estimating the correlation param-eter in current GEE software for binary responses disregard these bounds. To show that the GEE applied on binary data has high efficiency, we use a multivariate binary model so that the covariance matrix from estimating equation theory can be compared with the inverse Fisher information matrix. But R ( α ) should be viewed as the weight matrix, and it should not be confused with the correlation matrix of the binary responses. We also do a comparison with more general weighted estimating equations by using a matrix Cauchy–Schwarz inequality. Our analysis leads to simple rules for the choice of α in an exchangeable or autoregressive AR(1) weight matrix R ( α ), based on the strength of dependence between the binary variables. An example is given to illustrate the assessment of dependence and choice of α .     

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.     

Resistant fits for regression with correlated outcomes an estimating equations approach

The generalized estimating equations procedure of Liang and Zeger (1986) can be highly influenced by the presence of unusual data points. A generalization is introduced which yields parameter estimates and fitted values resistant to influential data. A diagonal weight matrix for each cluster is incorporated into the estimating equations which downweights the multivariate response vector element-wise. Efficiency of the procedure is investigated, including the case of correlated binary outcomes.     

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.     

Robust binary regression

Robust procedures increase the reliability of the results of a data analysis. We studied such a robust procedure for binary regression models based on the criterion of least absolute deviation. The resulting estimating equation consists in a simple modification of the familiar maximum likelihood equation. This estimator is easy to compute with existing computational procedures and gives a high degree of protection.     

A note on empirical likelihoods derived from pairwise score functions

Pairwise likelihood functions are convenient surrogates for the ordinary likelihood, useful when the latter is too difficult or even impractical to compute. One drawback of pairwise likelihood inference is that, for a multidimensional parameter of interest, the pairwise likelihood analogue of the likelihood ratio statistic does not have the standard chi-square asymptotic distribution. Invoking the theory of unbiased estimating functions, this paper proposes and discusses a computationally and theoretically attractive approach based on the derivation of empirical likelihood functions from the pairwise scores. This approach produces alternatives to the pairwise likelihood ratio statistic, which allow reference to the usual asymptotic chi-square distribution and which are useful when the elements of the Godambe information are troublesome to evaluate or in the presence of large data sets with relative small sample sizes. Two Monte Carlo studies are performed in order to assess the finite-sample performance of the proposed empirical pairwise likelihoods.     

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.     

Analyzing multivariate longitudinal binary data: A generalized estimating equations approach

The authors consider regression analysis for binary data collected repeatedly over time on members of numerous small clusters of individuals sharing a common random effect that induces dependence among them. They propose a mixed model that can accommodate both these structural and longitudinal dependencies. They estimate the parameters of the model consistently and efficiently using generalized estimating equations. They show through simulations that their approach yields significant gains in mean squared error when estimating the random effects variance and the longitudinal correlations, while providing estimates of the fixed effects that are just as precise as under a generalized penalized quasi‐likelihood approach. Their method is illustrated using smoking prevention data.     

On the application of extended quasi‐likelihood to the clustered data case

The author describes the relationship between the extended generalized estimating equations (EGEEs) of Hall & Severini (1998) and various similar methods. He proposes a true extended quasi‐likelihood approach for the clustered data case and explores restricted maximum likelihood‐like versions of the EGEE and extended quasi‐likelihood estimating equations. He also presents simulation results comparing the various estimators in terms of mean squared error of estimation based on three moderate sample size, discrete data situations.     

A two-stage estimation in the Clayton–Oakes model with marginal linear transformation models for multivariate failure time data

This paper considers the analysis of multivariate survival data where the marginal distributions are specified by semiparametric transformation models, a general class including the Cox model and the proportional odds model as special cases. First, consideration is given to the situation where the joint distribution of all failure times within the same cluster is specified by the Clayton–Oakes model (Clayton, Biometrika 65:141–151, l978; Oakes, J R Stat Soc B 44:412–422, 1982). A two-stage estimation procedure is adopted by first estimating the marginal parameters under the independence working assumption, and then the association parameter is estimated from the maximization of the full likelihood function with the estimators of the marginal parameters plugged in. The asymptotic properties of all estimators in the semiparametric model are derived. For the second situation, the third and higher order dependency structures are left unspecified, and interest focuses on the pairwise correlation between any two failure times. Thus, the pairwise association estimate can be obtained in the second stage by maximizing the pairwise likelihood function. Large sample properties for the pairwise association are also derived. Simulation studies show that the proposed approach is appropriate for practical use. To illustrate, a subset of the data from the Diabetic Retinopathy Study is used.     

Multiple imputation compared with restricted pseudo‐likelihood and generalized estimating equations for analysis of binary repeated measures in clinical studies

Non‐likelihood‐based methods for repeated measures analysis of binary data in clinical trials can result in biased estimates of treatment effects and associated standard errors when the dropout process is not completely at random. We tested the utility of a multiple imputation approach in reducing these biases. Simulations were used to compare performance of multiple imputation with generalized estimating equations and restricted pseudo‐likelihood in five representative clinical trial profiles for estimating (a) overall treatment effects and (b) treatment differences at the last scheduled visit. In clinical trials with moderate to high (40–60%) dropout rates with dropouts missing at random, multiple imputation led to less biased and more precise estimates of treatment differences for binary outcomes based on underlying continuous scores. Copyright © 2005 John Wiley & Sons, Ltd.     

Analysis of longitudinal multiple-source binary data using generalized estimating equations

Summary.  We present a multivariate logistic regression model for the joint analysis of longitudinal multiple-source binary data. Longitudinal multiple-source binary data arise when repeated binary measurements are obtained from two or more sources, with each source providing a measure of the same underlying variable. Since the number of responses on each subject is relatively large, the empirical variance estimator performs poorly and cannot be relied on in this setting. Two methods for obtaining a parsimonious within-subject association structure are considered. An additional complication arises with estimation, since maximum likelihood estimation may not be feasible without making unrealistically strong assumptions about third- and higher order moments. To circumvent this, we propose the use of a generalized estimating equations approach. Finally, we present an analysis of multiple-informant data obtained longitudinally from a psychiatric interventional trial that motivated the model developed in the paper.     

A new sequential approximation method

A sequential method for estimating the expected value of a random variable is proposed. Using a parametric model, the updating formula is based on the maximum likelihood estimators of the roots of the expected value function. Under certain conditions, it is demonstrated that the estimators of the roots are consistent, when a two-parameter logit model version of the procedure is used for binary data. In addition, the estimators of the logit parameters have an asymptotic normal distribution. A simulation study is performed to evaluate the effectiveness of the new method for small to medium sample sizes. Compared to other sequential approximation methods, the proposed method performed well, especially when estimating several roots simultaneously.     

Semi-parametric modelling and likelihood estimation with estimating equations

This paper proposes a semi-parametric modelling and estimating method for analysing censored survival data. The proposed method uses the empirical likelihood function to describe the information in data, and formulates estimating equations to incorporate knowledge of the underlying distribution and regression structure. The method is more flexible than the traditional methods such as the parametric maximum likelihood estimation (MLE), Cox's (1972) proportional hazards model, accelerated life test model, quasi-likelihood (Wedderburn, 1974) and generalized estimating equations (Liang & Zeger, 1986). This paper shows the existence and uniqueness of the proposed semi-parametric maximum likelihood estimates (SMLE) with estimating equations. The method is validated with known cases studied in the literature. Several finite sample simulation and large sample efficiency studies indicate that when the sample size is larger than 100 the SMLE is compatible with the parametric MLE; and in all case studies, the SMLE is about 15% better than the parametric MLE with a mis-specified underlying distribution.     

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.     

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.     

A robust pairwise likelihood method for incomplete longitudinal binary data arising in clusters

Clustered longitudinal data feature cross‐sectional associations within clusters, serial dependence within subjects, and associations between responses at different time points from different subjects within the same cluster. Generalized estimating equations are often used for inference with data of this sort since they do not require full specification of the response model. When data are incomplete, however, they require data to be missing completely at random unless inverse probability weights are introduced based on a model for the missing data process. The authors propose a robust approach for incomplete clustered longitudinal data using composite likelihood. Specifically, pairwise likelihood methods are described for conducting robust estimation with minimal model assumptions made. The authors also show that the resulting estimates remain valid for a wide variety of missing data problems including missing at random mechanisms and so in such cases there is no need to model the missing data process. In addition to describing the asymptotic properties of the resulting estimators, it is shown that the method performs well empirically through simulation studies for complete and incomplete data. Pairwise likelihood estimators are also compared with estimators obtained from inverse probability weighted alternating logistic regression. An application to data from the Waterloo Smoking Prevention Project is provided for illustration. The Canadian Journal of Statistics 39: 34–51; 2011 © 2010 Statistical Society of Canada