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.     

INCOMPLETE DATA IN GENERALIZED LINEAR MODELS WITH CONTINUOUS COVARIATES

This paper proposes a method for estimating the parameters in a generalized linear model with missing covariates. The missing covariates are assumed to come from a continuous distribution, and are assumed to be missing at random. In particular, Gaussian quadrature methods are used on the E-step of the EM algorithm, leading to an approximate EM algorithm. The parameters are then estimated using the weighted EM procedure given in Ibrahim (1990). This approximate EM procedure leads to approximate maximum likelihood estimates, whose standard errors and asymptotic properties are given. The proposed procedure is illustrated on a data set.     

Model selection of generalized partially linear models with missing covariates

In this paper, a generalized partially linear model (GPLM) with missing covariates is studied and a Monte Carlo EM (MCEM) algorithm with penalized-spline (P-spline) technique is developed to estimate the regression coefficients and nonparametric function, respectively. As classical model selection procedures such as Akaike's information criterion become invalid for our considered models with incomplete data, some new model selection criterions for GPLMs with missing covariates are proposed under two different missingness mechanism, say, missing at random (MAR) and missing not at random (MNAR). The most attractive point of our method is that it is rather general and can be extended to various situations with missing observations based on EM algorithm, especially when no missing data involved, our new model selection criterions are reduced to classical AIC. Therefore, we can not only compare models with missing observations under MAR/MNAR settings, but also can compare missing data models with complete-data models simultaneously. Theoretical properties of the proposed estimator, including consistency of the model selection criterions are investigated. A simulation study and a real example are used to illustrate the proposed methodology.     

Cure rate survival models with missing covariates: a simulation study

In this paper we study the cure rate survival model involving a competitive risk structure with missing categorical covariates. A parametric distribution that can be written as a sequence of one-dimensional conditional distributions is specified for the missing covariates. We consider the missing data at random situation so that the missing covariates may depend only on the observed ones. Parameter estimates are obtained by using the EM algorithm via the method of weights. Extensive simulation studies are conducted and reported to compare estimates efficiency with and without missing data. As expected, the estimation approach taking into consideration the missing covariates presents much better efficiency in terms of mean square errors than the complete case situation. Effects of increasing cured fraction and censored observations are also reported. We demonstrate the proposed methodology with two real data sets. One involved the length of time to obtain a BS degree in Statistics, and another about the time to breast cancer recurrence.     

Missing covariates in generalized linear models when the missing data mechanism is non-ignorable

We propose a method for estimating parameters in generalized linear models with missing covariates and a non-ignorable missing data mechanism. We use a multinomial model for the missing data indicators and propose a joint distribution for them which can be written as a sequence of one-dimensional conditional distributions, with each one-dimensional conditional distribution consisting of a logistic regression. We allow the covariates to be either categorical or continuous. The joint covariate distribution is also modelled via a sequence of one-dimensional conditional distributions, and the response variable is assumed to be completely observed. We derive the E- and M-steps of the EM algorithm with non-ignorable missing covariate data. For categorical covariates, we derive a closed form expression for the E- and M-steps of the EM algorithm for obtaining the maximum likelihood estimates (MLEs). For continuous covariates, we use a Monte Carlo version of the EM algorithm to obtain the MLEs via the Gibbs sampler. Computational techniques for Gibbs sampling are proposed and implemented. The parametric form of the assumed missing data mechanism itself is not `testable' from the data, and thus the non-ignorable modelling considered here can be viewed as a sensitivity analysis concerning a more complicated model. Therefore, although a model may have `passed' the tests for a certain missing data mechanism, this does not mean that we have captured, even approximately, the correct missing data mechanism. Hence, model checking for the missing data mechanism and sensitivity analyses play an important role in this problem and are discussed in detail. Several simulations are given to demonstrate the methodology. In addition, a real data set from a melanoma cancer clinical trial is presented to illustrate the methods proposed.     

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.     

Joint regression modeling for missing categorical covariates in generalized linear models

Missing covariates data is a common issue in generalized linear models (GLMs). A model-based procedure arising from properly specifying joint models for both the partially observed covariates and the corresponding missing indicator variables represents a sound and flexible methodology, which lends itself to maximum likelihood estimation as the likelihood function is available in computable form. In this paper, a novel model-based methodology is proposed for the regression analysis of GLMs when the partially observed covariates are categorical. Pair-copula constructions are used as graphical tools in order to facilitate the specification of the high-dimensional probability distributions of the underlying missingness components. The model parameters are estimated by maximizing the weighted log-likelihood function by using an EM algorithm. In order to compare the performance of the proposed methodology with other well-established approaches, which include complete-cases and multiple imputation, several simulation experiments of Binomial, Poisson and Normal regressions are carried out under both missing at random and non-missing at random mechanisms scenarios. The methods are illustrated by modeling data from a stage III melanoma clinical trial. The results show that the methodology is rather robust and flexible, representing a competitive alternative to traditional techniques.     

A SEMIPARAMETRIC REGRESSION MODEL WITH MISSING COVARIATES IN CONTINUOUS-TIME CAPTURE-RECAPTURE STUDIES

Covariate data were missing when a semiparametric regression model was used to study bird abundance in the Mai Po Sanctuary, Hong Kong. This paper proposes an EM‐type algorithm to estimate the regression parameters for that study. Analytical calculation of the expectation in the EM method is difficult, or even impossible, especially when missing covariates are continuous. A Monte Carlo method is used in the EM algorithm to ease the calculation complexity. Asymptotic variances of the parameter estimates are also derived. Properties of the proposed estimators are assessed through numerical simulations and a real example.     

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.     

Incomplete covariates data in generalized linear models

We consider regression analysis when part of covariates are incomplete in generalized linear models. The incomplete covariates could be due to measurement error or missing for some study subjects. We assume there exists a validation sample in which the data is complete and is a simple random subsample from the whole sample. Based on the idea of projection-solution method in Heyde (1997, Quasi-Likelihood and its Applications: A General Approach to Optimal Parameter Estimation. Springer, New York), a class of estimating functions is proposed to estimate the regression coefficients through the whole data. This method does not need to specify a correct parametric model for the incomplete covariates to yield a consistent estimate, and avoids the ‘curse of dimensionality’ encountered in the existing semiparametric method. Simulation results shows that the finite sample performance and efficiency property of the proposed estimates are satisfactory. Also this approach is computationally convenient hence can be applied to daily data analysis.     

Using the EM-algorithm for survival data with incomplete categorical covariates

Incomplete covariate data is a common occurrence in many studies in which the outcome is survival time. With generalized linear models, when the missing covariates are categorical, a useful technique for obtaining parameter estimates is the EM by the method of weights proposed in Ibrahim (1990). In this article, we extend the EM by the method of weights to survival outcomes whose distributions may not fall in the class of generalized linear models. This method requires the estimation of the parameters of the distribution of the covariates. We present a clinical trials example with five covariates, four of which have some missing values.     

Multiple imputation of censored survival data in the presence of missing covariates using restricted mean survival time

Missing covariates data with censored outcomes put a challenge in the analysis of clinical data especially in small sample settings. Multiple imputation (MI) techniques are popularly used to impute missing covariates and the data are then analyzed through methods that can handle censoring. However, techniques based on MI are available to impute censored data also but they are not much in practice. In the present study, we applied a method based on multiple imputation by chained equations to impute missing values of covariates and also to impute censored outcomes using restricted survival time in small sample settings. The complete data were then analyzed using linear regression models. Simulation studies and a real example of CHD data show that the present method produced better estimates and lower standard errors when applied on the data having missing covariate values and censored outcomes than the analysis of the data having censored outcome but excluding cases with missing covariates or the analysis when cases with missing covariate values and censored outcomes were excluded from the data (complete case analysis).     

Estimating Transition Probabilities for Ignorable Intermittent Missing Data in a Discrete-Time Markov Chain

This article considers a discrete-time Markov chain for modeling transition probabilities when multiple successive observations are missing at random between two observed outcomes using three methods: a na\"?ve analog of complete-case analysis using the observed one-step transitions alone, a non data-augmentation method (NL) by solving nonlinear equations, and a data-augmentation method, the Expectation-Maximization (EM) algorithm. The explicit form of the conditional log-likelihood given the observed information as required by the E step is provided, and the iterative formula in the M step is expressed in a closed form. An empirical study was performed to examine the accuracy and precision of the estimates obtained in the three methods under ignorable missing mechanisms of missing completely at random and missing at random. A dataset from the mental health arena was used for illustration. It was found that both data-augmentation and nonaugmentation methods provide accurate and precise point estimation, and that the na\"?ve method resulted in estimates of the transition probabilities with similar bias but larger MSE. The NL method and the EM algorithm in general provide similar results whereas the latter provides conditional expected row margins leading to smaller standard errors.     

Information attainable in some randomly incomplete multivariate response models

In a general parametric setup, a multivariate regression model is considered when responses may be missing at random while the explanatory variables and covariates are completely observed. Asymptotic optimality properties of maximum likelihood estimators for such models are linked to the Fisher information matrix for the parameters. It is shown that the information matrix is well defined for the missing-at-random model and that it plays the same role as in the complete-data linear models. Applications of the methodologic developments in hypothesis-testing problems, without any imputation of missing data, are illustrated. Some simulation results comparing the proposed method with Rubin's multiple imputation method are presented.     

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.     

A cautionary note on generalized linear models for covariance of unbalanced longitudinal data

Missing data in longitudinal studies can create enormous challenges in data analysis when coupled with the positive-definiteness constraint on a covariance matrix. For complete balanced data, the Cholesky decomposition of a covariance matrix makes it possible to remove the positive-definiteness constraint and use a generalized linear model setup to jointly model the mean and covariance using covariates (Pourahmadi, 2000). However, this approach may not be directly applicable when the longitudinal data are unbalanced, as coherent regression models for the dependence across all times and subjects may not exist. Within the existing generalized linear model framework, we show how to overcome this and other challenges by embedding the covariance matrix of the observed data for each subject in a larger covariance matrix and employing the familiar EM algorithm to compute the maximum likelihood estimates of the parameters and their standard errors. We illustrate and assess the methodology using real data sets and simulations.     

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.     

Missing values: sparse inverse covariance estimation and?an?extension to sparse regression

We propose an ℓ ₁-regularized likelihood method for estimating the inverse covariance matrix in the high-dimensional multivariate normal model in presence of missing data. Our method is based on the assumption that the data are missing at random (MAR) which entails also the completely missing at random case. The implementation of the method is non-trivial as the observed negative log-likelihood generally is a complicated and non-convex function. We propose an efficient EM algorithm for optimization with provable numerical convergence properties. Furthermore, we extend the methodology to handle missing values in a sparse regression context. We demonstrate both methods on simulated and real data.     

Empirical likelihood weighted composite quantile regression with partially missing covariates

This paper develops a novel weighted composite quantile regression (CQR) method for estimation of a linear model when some covariates are missing at random and the probability for missingness mechanism can be modelled parametrically. By incorporating the unbiased estimating equations of incomplete data into empirical likelihood (EL), we obtain the EL-based weights, and then re-adjust the inverse probability weighted CQR for estimating the vector of regression coefficients. Theoretical results show that the proposed method can achieve semiparametric efficiency if the selection probability function is correctly specified, therefore the EL weighted CQR is more efficient than the inverse probability weighted CQR. Besides, our algorithm is computationally simple and easy to implement. Simulation studies are conducted to examine the finite sample performance of the proposed procedures. Finally, we apply the new method to analyse the US news College data.     

Incomplete covariates in the Cox model with applications to biological marker data

A common occurrence in clinical trials with a survival end point is missing covariate data. With ignorably missing covariate data, Lipsitz and Ibrahim proposed a set of estimating equations to estimate the parameters of Cox's proportional hazards model. They proposed to obtain parameter estimates via a Monte Carlo EM algorithm. We extend those results to non-ignorably missing covariate data. We present a clinical trials example with three partially observed laboratory markers which are used as covariates to predict survival.