Covariate Decomposition Methods for Longitudinal Missing‐at‐Random Data and Predictors Associated with Subject‐Specific Effects

Investigators often gather longitudinal data to assess changes in responses over time within subjects and to relate these changes to within‐subject changes in predictors. Missing data are common in such studies and predictors can be correlated with subject‐specific effects. Maximum likelihood methods for generalized linear mixed models provide consistent estimates when the data are ‘missing at random’ (MAR) but can produce inconsistent estimates in settings where the random effects are correlated with one of the predictors. On the other hand, conditional maximum likelihood methods (and closely related maximum likelihood methods that partition covariates into between‐ and within‐cluster components) provide consistent estimation when random effects are correlated with predictors but can produce inconsistent covariate effect estimates when data are MAR. Using theory, simulation studies, and fits to example data this paper shows that decomposition methods using complete covariate information produce consistent estimates. In some practical cases these methods, that ostensibly require complete covariate information, actually only involve the observed covariates. These results offer an easy‐to‐use approach to simultaneously protect against bias from both cluster‐level confounding and MAR missingness in assessments of change.     

Sparse Functional Principal Component Analysis via Regularized Basis Expansions and Its Application

This article introduces principal component analysis for multidimensional sparse functional data, utilizing Gaussian basis functions. Our multidimensional model is estimated by maximizing a penalized log-likelihood function, while previous mixed-type models were estimated by maximum likelihood methods for one-dimensional data. The penalized estimation performs well for our multidimensional model, while maximum likelihood methods yield unstable parameter estimates and some of the parameter estimates are infinite. Numerical experiments are conducted to investigate the effectiveness of our method for some types of missing data. The proposed method is applied to handwriting data, which consist of the XY coordinates values in handwritings.     

A Profile Conditional Likelihood Approach for the Semiparametric Transformation Regression Model with Missing Covariates

We propose a profile conditional likelihood approach to handle missing covariates in the general semiparametric transformation regression model. The method estimates the marginal survival function by the Kaplan-Meier estimator, and then estimates the parameters of the survival model and the covariate distribution from a conditional likelihood, substituting the Kaplan-Meier estimator for the marginal survival function in the conditional likelihood. This method is simpler than full maximum likelihood approaches, and yields consistent and asymptotically normally distributed estimator of the regression parameter when censoring is independent of the covariates. The estimator demonstrates very high relative efficiency in simulations. When compared with complete-case analysis, the proposed estimator can be more efficient when the missing data are missing completely at random and can correct bias when the missing data are missing at random. The potential application of the proposed method to the generalized probit model with missing continuous covariates is also outlined.     

Robust methods for generalized linear models with nonignorable missing covariates

The EM algorithm is often used for finding the maximum likelihood estimates in generalized linear models with incomplete data. In this article, the author presents a robust method in the framework of the maximum likelihood estimation for fitting generalized linear models when nonignorable covariates are missing. His robust approach is useful for downweighting any influential observations when estimating the model parameters. To avoid computational problems involving irreducibly high‐dimensional integrals, he adopts a Metropolis‐Hastings algorithm based on a Markov chain sampling method. He carries out simulations to investigate the behaviour of the robust estimates in the presence of outliers and missing covariates; furthermore, he compares these estimates to the classical maximum likelihood estimates. Finally, he illustrates his approach using data on the occurrence of delirium in patients operated on for abdominal aortic aneurysm.     

Bias correction in logistic regression with missing categorical covariates

Logistic regression plays an important role in many fields. In practice, we often encounter missing covariates in different applied sectors, particularly in biomedical sciences. Ibrahim (1990) proposed a method to handle missing covariates in generalized linear model (GLM) setup. It is well known that logistic regression estimates using small or medium sized missing data are biased. Considering the missing data that are missing at random, in this paper we have reduced the bias by two methods; first we have derived a closed form bias expression using Cox and Snell (1968), and second we have used likelihood based modification similar to Firth (1993). Here we have analytically shown that the Firth type likelihood modification in Ibrahim led to the second order bias reduction. The proposed methods are simple to apply on an existing method, need no analytical work, with the exception of a little change in the optimization function. We have carried out extensive simulation studies comparing the methods, and our simulation results are also supported by a real world data.     

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     

Latent class based multiple imputation approach for missing categorical data

In this paper we propose a latent class based multiple imputation approach for analyzing missing categorical covariate data in a highly stratified data model. In this approach, we impute the missing data assuming a latent class imputation model and we use likelihood methods to analyze the imputed data. Via extensive simulations, we study its statistical properties and make comparisons with complete case analysis, multiple imputation, saturated log-linear multiple imputation and the Expectation–Maximization approach under seven missing data mechanisms (including missing completely at random, missing at random and not missing at random). These methods are compared with respect to bias, asymptotic standard error, type I error, and 95% coverage probabilities of parameter estimates. Simulations show that, under many missingness scenarios, latent class multiple imputation performs favorably when jointly considering these criteria. A data example from a matched case–control study of the association between multiple myeloma and polymorphisms of the Inter-Leukin 6 genes is considered.     

Analysis of ordinal outcomes with longitudinal covariates subject to missingness

We propose a mixture model for data with an ordinal outcome and a longitudinal covariate that is subject to missingness. Data from a tailored telephone delivered, smoking cessation intervention for construction laborers are used to illustrate the method, which considers as an outcome a categorical measure of smoking cessation, and evaluates the effectiveness of the motivational telephone interviews on this outcome. We propose two model structures for the longitudinal covariate, for the case when the missing data are missing at random, and when the missing data mechanism is non-ignorable. A generalized EM algorithm is used to obtain maximum likelihood estimates.     

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.     

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.     

Parametric fractional imputation for nonignorable missing data

Parameter estimation with missing data is a frequently encountered problem in statistics. Imputation is often used to facilitate the parameter estimation by simply applying the complete-sample estimators to the imputed dataset.In this article, we consider the problem of parameter estimation with nonignorable missing data using the approach of parametric fractional imputation proposed by Kim (2011). Using the fractional weights, the E-step of the EM algorithm can be approximated by the weighted mean of the imputed data likelihood where the fractional weights are computed from the current value of the parameter estimates. Calibration fractional imputation is also considered as a way for improving the Monte Carlo approximation in the fractional imputation. Variance estimation is also discussed. Results from two simulation studies are presented to compare the proposed method with the existing methods. A real data example from the Korea Labor and Income Panel Survey (KLIPS) is also presented.     

Inference on unknown parameters of a Burr distribution under hybrid censoring

Based on hybrid censored data, the problem of making statistical inference on parameters of a two parameter Burr Type XII distribution is taken up. The maximum likelihood estimates are developed for the unknown parameters using the EM algorithm. Fisher information matrix is obtained by applying missing value principle and is further utilized for constructing the approximate confidence intervals. Some Bayes estimates and the corresponding highest posterior density intervals of the unknown parameters are also obtained. Lindley’s approximation method and a Markov Chain Monte Carlo (MCMC) technique have been applied to evaluate these Bayes estimates. Further, MCMC samples are utilized to construct the highest posterior density intervals as well. A numerical comparison is made between proposed estimates in terms of their mean square error values and comments are given. Finally, two data sets are analyzed using proposed methods.     

Inference based on progressive Type I interval censored data from log-normal distribution

This article considers inference for the log-normal distribution based on progressive Type I interval censored data by both frequentist and Bayesian methods. First, the maximum likelihood estimates (MLEs) of the unknown model parameters are computed by expectation-maximization (EM) algorithm. The asymptotic standard errors (ASEs) of the MLEs are obtained by applying the missing information principle. Next, the Bayes’ estimates of the model parameters are obtained by Gibbs sampling method under both symmetric and asymmetric loss functions. The Gibbs sampling scheme is facilitated by adopting a similar data augmentation scheme as in EM algorithm. The performance of the MLEs and various Bayesian point estimates is judged via a simulation study. A real dataset is analyzed for the purpose of illustration.     

Cox Regression with Incomplete Covariate Measurements using the EM-algorithm

Ibrahim (1990) used the EM-algorithm to obtain maximum likelihood estimates of the regression parameters in generalized linear models with partially missing covariates. The technique was termed EM by the method of weights. In this paper, we generalize this technique to Cox regression analysis with missing values in the covariates. We specify a full model letting the unobserved covariate values be random and then maximize the observed likelihood. The asymptotic covariance matrix is estimated by the inverse information matrix. The missing data are allowed to be missing at random but also the non-ignorable non-response situation may in principle be considered. Simulation studies indicate that the proposed method is more efficient than the method suggested by Paik & Tsai (1997). We apply the procedure to a clinical trials example with six covariates with three of them having missing values.     

Approximate bounded influence estimation for longitudinal data with outliers and measurement errors

Mixed effects models or random effects models are popular for the analysis of longitudinal data. In practice, longitudinal data are often complex since there may be outliers in both the response and the covariates and there may be measurement errors. The likelihood method is a common approach for these problems but it can be computationally very intensive and sometimes may even be computationally infeasible. In this article, we consider approximate robust methods for nonlinear mixed effects models to simultaneously address outliers and measurement errors. The approximate methods are computationally very efficient. We show the consistency and asymptotic normality of the approximate estimates. The methods can also be extended to missing data problems. An example is used to illustrate the methods and a simulation is conducted to evaluate the methods.     

The em algorithm for the quasi-likelihood regression model

The objective of this paper is to present a method which can accommodate certain types of missing data by using the quasi-likelihood function for the complete data. This method can be useful when we can make first and second moment assumptions only; in addition, it can be helpful when the EM algorithm applied to the actual likelihood becomes overly complicated. First we derive a loss function for the observed data using an exponential family density which has the same mean and variance structure of the complete data. This loss function is the counterpart of the quasi-deviance for the observed data. Then the loss function is minimized using the EM algorithm. The use of the EM algorithm guarantees a decrease in the loss function at every iteration. When the observed data can be expressed as a deterministic linear transformation of the complete data, or when data are missing completely at random, the proposed method yields consistent estimators. Examples are given for overdispersed polytomous data, linear random effects models, and linear regression with missing covariates. Simulation results for the linear regression model with missing covariates show that the proposed estimates are more efficient than estimates based on completely observed units, even when outcomes are bimodal or skewed.     

Some asymptotic results for semiparametric nonlinear mixed-effects models with incomplete data

In modeling complex longitudinal data, semiparametric nonlinear mixed-effects (SNLME) models are very flexible and useful. Covariates are often introduced in the models to partially explain the inter-individual variations. In practice, data are often incomplete in the sense that there are often measurement errors and missing data in longitudinal studies. The likelihood method is a standard approach for inference for these models but it can be computationally very challenging, so computationally efficient approximate methods are quite valuable. However, the performance of these approximate methods is often based on limited simulation studies, and theoretical results are unavailable for many approximate methods. In this article, we consider a computationally efficient approximate method for a class of SNLME models with incomplete data and investigate its theoretical properties. We show that the estimates based on the approximate method are consistent and asymptotically normally distributed.     

Missing data techniques for multilevel data: implications of model misspecification

When modeling multilevel data, it is important to accurately represent the interdependence of observations within clusters. Ignoring data clustering may result in parameter misestimation. However, it is not well established to what degree parameter estimates are affected by model misspecification when applying missing data techniques (MDTs) to incomplete multilevel data. We compare the performance of three MDTs with incomplete hierarchical data. We consider the impact of imputation model misspecification on the quality of parameter estimates by employing multiple imputation under assumptions of a normal model (MI/NM) with two-level cross-sectional data when values are missing at random on the dependent variable at rates of 10%, 30%, and 50%. Five criteria are used to compare estimates from MI/NM to estimates from MI assuming a linear mixed model (MI/LMM) and maximum likelihood estimation to the same incomplete data sets. With 10% missing data (MD), techniques performed similarly for fixed-effects estimates, but variance components were biased with MI/NM. Effects of model misspecification worsened at higher rates of MD, with the hierarchical structure of the data markedly underrepresented by biased variance component estimates. MI/LMM and maximum likelihood provided generally accurate and unbiased parameter estimates but performance was negatively affected by increased rates of MD.     

Use of Orthogonal Polynomial Approximations for Inference in Exponential Distribution Based on K-Sample Doubly Type-II Censored Data

In this article, an EM algorithm approach to obtain the maximum likelihood estimates of parameters for analyzing bivariate skew normal data with non monotone missing values is presented. A simulation study is implemented to investigate the performance of the presented algorithm. Results of an application are also reported where a Bootstrap approach is used to find the variances of the parameter estimates.     

The factoring likelihood method for non-monotone missing data

We address the problem of parameter estimation in multivariate distributions under ignorable non-monotone missing data. The factoring likelihood method for monotone missing data, termed by Rubin (1974), is applied to a more general case of non-monotone missing data. The proposed method is asymptotically equivalent to the Fisher scoring method from the observed likelihood, but avoids the burden of computing the first and second partial derivatives of the observed likelihood. Instead, the maximum likelihood estimates and their information matrices for each partition of the data set are computed separately and combined naturally using the generalized least squares method. A numerical example is presented to illustrate the method.