Goodness-of-fit tests for general linear models with covariates missed at random

In this paper, we consider a model checking problem for general linear models with randomly missing covariates. Two types of score type tests with inverse probability weight, which is estimated by parameter and nonparameter methods respectively, are proposed to this goodness of fit problem. The asymptotic properties of the test statistics are developed under the null and local alternative hypothesis. Simulation study is carried out to present the performance of the sizes and powers of the tests. We illustrate the proposed method with a data set on monozygotic twins.     

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.     

Methods for missing covariates in logistic regression

Various methods have been suggested in the literature to handle a missing covariate in the presence of surrogate covariates. These methods belong to one of two paradigms. In the imputation paradigm, Pepe and Fleming (1991) and Reilly and Pepe (1995) suggested filling in missing covariates using the empirical distribution of the covariate obtained from the observed data. We can proceed one step further by imputing the missing covariate using nonparametric maximum likelihood estimates (NPMLE) of the density of the covariate. Recently Murphy and Van der Vaart (1998a) showed that such an approach yields a consistent, asymptotically normal, and semiparametric efficient estimate for the logistic regression coefficient. In the weighting paradigm, Zhao and Lipsitz (1992) suggested an estimating function using completely observed records after weighting inversely by the probability of observation. An extension of this weighting approach designed to achieve semiparametric efficient bound is considered by Robins, Hsieh and Newey (RHN) (1995). The two ends of each paradigm (NPMLE and RHN) attain the efficiency bound and are asymptotically equivalent. However, both require a substantial amount of computation. A question arises whether and when, in practical situations, this extensive computation is worthwhile. In this paper we investigate the performance of single and multiple imputation estimates, weighting estimates, semiparametric efficient estimates, and two new imputation estimates. Simulation studies suggest that the sample size should be substantially large (e.g. n=2000) for NPMLE and RHN to be more efficient than simpler imputation estimates. When the sample size is moderately large (n≤ 1500), simpler imputation estimates have as small a variance as semiparametric efficient estimates.     

Estimation of the additive hazards model with interval-censored data and missing covariates

The additive hazards model is one of the most commonly used regression models in the analysis of failure time data and many methods have been developed for its inference in various situations. However, no established estimation procedure exists when there are covariates with missing values and the observed responses are interval-censored; both types of complications arise in various settings including demographic, epidemiological, financial, medical and sociological studies. To address this deficiency, we propose several inverse probability weight-based and reweighting-based estimation procedures for the situation where covariate values are missing at random. The resulting estimators of regression model parameters are shown to be consistent and asymptotically normal. The numerical results that we report from a simulation study suggest that the proposed methods work well in practical situations. An application to a childhood cancer survival study is provided. The Canadian Journal of Statistics 48: 499–517; 2020 © 2020 Statistical Society of Canada     

Regression analysis under non-standard situations: a pairwise pseudolikelihood approach

Regression analysis is one of the most used statistical methods for data analysis. There are, however, many situations in which one cannot base inference solely on f ( y ∣ x ; β), the conditional probability (density) function for the response variable Y , given x , the covariates. Examples include missing data where the missingness is non-ignorable, sampling surveys in which subjects are selected on the basis of the Y -values and meta-analysis where published studies are subject to 'selection bias'. The conventional approaches require the correct specification of the missingness mechanism, sampling probability and probability for being published respectively. In this paper, we propose an alternative estimating procedure for β based on an idea originated by Kalbfleisch. The novelty of this method is that no assumption on the missingness probability mechanisms etc. mentioned above is required to be specified. Asymptotic efficiency calculations and simulation studies were conducted to compare the method proposed with the two existing methods: the conditional likelihood and the weighted estimating function approaches.     

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).     

Efficient inverse probability weighting method for quantile regression with nonignorable missing data

Quantitle regression (QR) is a popular approach to estimate functional relations between variables for all portions of a probability distribution. Parameter estimation in QR with missing data is one of the most challenging issues in statistics. Regression quantiles can be substantially biased when observations are subject to missingness. We study several inverse probability weighting (IPW) estimators for parameters in QR when covariates or responses are subject to missing not at random. Maximum likelihood and semiparametric likelihood methods are employed to estimate the respondent probability function. To achieve nice efficiency properties, we develop an empirical likelihood (EL) approach to QR with the auxiliary information from the calibration constraints. The proposed methods are less sensitive to misspecified missing mechanisms. Asymptotic properties of the proposed IPW estimators are shown under general settings. The efficiency gain of EL-based IPW estimator is quantified theoretically. Simulation studies and a data set on the work limitation of injured workers from Canada are used to illustrated our proposed methodologies.     

Bayesian Methods for Missing Covariates in Cure Rate Models

We propose methods for Bayesian inference for missing covariate data with a novel class of semi-parametric survival models with a cure fraction. We allow the missing covariates to be either categorical or continuous and specify a parametric distribution for the covariates that is written as a sequence of one dimensional conditional distributions. We assume that the missing covariates are missing at random (MAR) throughout. We propose an informative class of joint prior distributions for the regression coefficients and the parameters arising from the covariate distributions. The proposed class of priors are shown to be useful in recovering information on the missing covariates especially in situations where the missing data fraction is large. Properties of the proposed prior and resulting posterior distributions are examined. Also, model checking techniques are proposed for sensitivity analyses and for checking the goodness of fit of a particular model. Specifically, we extend the Conditional Predictive Ordinate (CPO) statistic to assess goodness of fit in the presence of missing covariate data. Computational techniques using the Gibbs sampler are implemented. A real data set involving a melanoma cancer clinical trial is examined to demonstrate the methodology.     

Calibrating covariate informed product partition models

Covariate informed product partition models incorporate the intuitively appealing notion that individuals or units with similar covariate values a priori have a higher probability of co-clustering than those with dissimilar covariate values. These methods have been shown to perform well if the number of covariates is relatively small. However, as the number of covariates increase, their influence on partition probabilities overwhelm any information the response may provide in clustering and often encourage partitions with either a large number of singleton clusters or one large cluster resulting in poor model fit and poor out-of-sample prediction. This same phenomenon is observed in Bayesian nonparametric regression methods that induce a conditional distribution for the response given covariates through a joint model. In light of this, we propose two methods that calibrate the covariate-dependent partition model by capping the influence that covariates have on partition probabilities. We demonstrate the new methods’ utility using simulation and two publicly available datasets.     

Semiparametric predictive mean matching

Predictive mean matching is an imputation method that combines parametric and nonparametric techniques. It imputes missing values by means of the Nearest Neighbor Donor with distance based on the expected values of the missing variables conditional on the observed covariates, instead of computing the distance directly on the values of the covariates. In ordinary predictive mean matching the expected values are computed through a linear regression model. In this paper a generalization of the original predictive mean matching is studied. Here the expected values used for computing the distance are estimated through an approach based on Gaussian mixture models. This approach includes as a special case the original predictive mean matching but allows one to deal also with nonlinear relationships among the variables. In order to assess its performance, an empirical evaluation based on simulations is carried out.     

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.     

Semiparametric methods for response-selective and missing data problems in regression

Suppose that data are generated according to the model f ( y | x ; θ ) g ( x ), where y is a response and x are covariates. We derive and compare semiparametric likelihood and pseudolikelihood methods for estimating θ for situations in which units generated are not fully observed and in which it is impossible or undesirable to model the covariate distribution. The probability that a unit is fully observed may depend on y , and there may be a subset of covariates which is observed only for a subsample of individuals. Our key assumptions are that the probability that a unit has missing data depends only on which of a finite number of strata that ( y , x ) belongs to and that the stratum membership is observed for every unit. Applications include case–control studies in epidemiology, field reliability studies and broad classes of missing data and measurement error problems. Our results make fully efficient estimation of θ feasible, and they generalize and provide insight into a variety of methods that have been proposed for specific problems.     

Combining Inverse Probability Weighting and Multiple Imputation to Improve Robustness of Estimation

Inverse probability weighting (IPW) and multiple imputation are two widely adopted approaches dealing with missing data. The former models the selection probability, and the latter models data distribution. Consistent estimation requires correct specification of corresponding models. Although the augmented IPW method provides an extra layer of protection on consistency, it is usually not sufficient in practice as the true data‐generating process is unknown. This paper proposes a method combining the two approaches in the same spirit of calibration in sampling survey literature. Multiple models for both the selection probability and data distribution can be simultaneously accounted for, and the resulting estimator is consistent if any model is correctly specified. The proposed method is within the framework of estimating equations and is general enough to cover regression analysis with missing outcomes and/or missing covariates. Results on both theoretical and numerical investigation are provided.     

The competing risks Cox model with auxiliary case covariates under weaker missing-at-random cause of failure

In the analysis of time-to-event data with multiple causes using a competing risks Cox model, often the cause of failure is unknown for some of the cases. The probability of a missing cause is typically assumed to be independent of the cause given the time of the event and covariates measured before the event occurred. In practice, however, the underlying missing-at-random assumption does not necessarily hold. Motivated by colorectal cancer molecular pathological epidemiology analysis, we develop a method to conduct valid analysis when additional auxiliary variables are available for cases only. We consider a weaker missing-at-random assumption, with missing pattern depending on the observed quantities, which include the auxiliary covariates. We use an informative likelihood approach that will yield consistent estimates even when the underlying model for missing cause of failure is misspecified. The superiority of our method over naive methods in finite samples is demonstrated by simulation study results. We illustrate the use of our method in an analysis of colorectal cancer data from the Nurses’ Health Study cohort, where, apparently, the traditional missing-at-random assumption fails to hold.     

Estimation of conditional cumulative incidence functions under generalized semiparametric regression models with missing covariates,with application to analysis of biomarker correlates in vaccine trials

This article presents generalized semiparametric regression models for conditional cumulative incidence functions with competing risks data when covariates are missing by sampling design or happenstance. A doubly robust augmented inverse probability weighted (AIPW) complete-case approach to estimation and inference is investigated. This approach modifies IPW complete-case estimating equations by exploiting the key features in the relationship between the missing covariates and the phase-one data to improve efficiency. An iterative numerical procedure is derived to solve the nonlinear estimating equations. The asymptotic properties of the proposed estimators are established. A simulation study examining the finite-sample performances of the proposed estimators shows that the AIPW estimators are more efficient than the IPW estimators. The developed method is applied to the RV144 HIV-1 vaccine efficacy trial to investigate vaccine-induced IgG binding antibodies to HIV-1 as correlates of acquisition of HIV-1 infection while taking account of whether the HIV-1 sequences are near or far from the HIV-1 sequences represented in the vaccine construct.     

Penalized inverse probability weighted estimators for weighted rank regression with missing covariates

Abstract

In this article, we study the variable selection and estimation for linear regression models with missing covariates. The proposed estimation method is almost as efficient as the popular least-squares-based estimation method for normal random errors and empirically shown to be much more efficient and robust with respect to heavy tailed errors or outliers in the responses and covariates. To achieve sparsity, a variable selection procedure based on SCAD is proposed to conduct estimation and variable selection simultaneously. The procedure is shown to possess the oracle property. To deal with the covariates missing, we consider the inverse probability weighted estimators for the linear model when the selection probability is known or unknown. It is shown that the estimator by using estimated selection probability has a smaller asymptotic variance than that with true selection probability, thus is more efficient. Therefore, the important Horvitz-Thompson property is verified for penalized rank estimator with the covariates missing in the linear model. Some numerical examples are provided to demonstrate the performance of the estimators.     

Probability density estimation with data missing at random when covariables are present

This paper addresses the problem of the probability density estimation in the presence of covariates when data are missing at random (MAR). The inverse probability weighted method is used to define a nonparametric and a semiparametric weighted probability density estimators. A regression calibration technique is also used to define an imputed estimator. It is shown that all the estimators are asymptotically normal with the same asymptotic variance as that of the inverse probability weighted estimator with known selection probability function and weights. Also, we establish the mean squared error (MSE) bounds and obtain the MSE convergence rates. A simulation is carried out to assess the proposed estimators in terms of the bias and standard error.     

Bayesian variable selection for the Cox regression model with missing covariates

In this paper, we develop Bayesian methodology and computational algorithms for variable subset selection in Cox proportional hazards models with missing covariate data. A new joint semi-conjugate prior for the piecewise exponential model is proposed in the presence of missing covariates and its properties are examined. The covariates are assumed to be missing at random (MAR). Under this new prior, a version of the Deviance Information Criterion (DIC) is proposed for Bayesian variable subset selection in the presence of missing covariates. Monte Carlo methods are developed for computing the DICs for all possible subset models in the model space. A Bone Marrow Transplant (BMT) dataset is used to illustrate the proposed methodology.     

Using number of failed contact attempts to adjust for non-ignorable non-response

Summary.  We present a general method of adjustment for non-ignorable non-response in studies where one or more further attempts are made to contact initial non-responders. A logistic regression model relates the probability of response at each contact attempt to covariates and outcomes of interest. We assume that the effect of these covariates and outcomes on the probability of response is the same at all contact attempts. Knowledge of the number of contact attempts enables estimation of the model by using only information from the respondents and the number of non-responders. Three approaches for fitting the response models and estimating parameters of substantive interest and their standard errors are compared: a modified conditional likelihood method in which the fitted inverse probabilities of response are used in weighted analyses for the outcomes of interest, an EM procedure with the Louis formula and a Bayesian approach using Markov chain Monte Carlo methods. We further propose the creation of several sets of weights to incorporate uncertainty in the probability weights in subsequent analyses. Our methods are applied as a sensitivity analysis to a postal survey of symptoms in Persian Gulf War veterans and other servicemen.     

Validity and efficiency in analyzing ordinal responses with missing observations

This article addresses issues in creating public-use data files in the presence of missing ordinal responses and subsequent statistical analyses of the dataset by users. The authors propose a fully efficient fractional imputation (FI) procedure for ordinal responses with missing observations. The proposed imputation strategy retrieves the missing values through the full conditional distribution of the response given the covariates and results in a single imputed data file that can be analyzed by different data users with different scientific objectives. Two most critical aspects of statistical analyses based on the imputed data set,  validity  and  efficiency, are examined through regression analysis involving the ordinal response and a selected set of covariates. It is shown through both theoretical development and simulation studies that, when the ordinal responses are missing at random, the proposed FI procedure leads to valid and highly efficient inferences as compared to existing methods. Variance estimation using the fractionally imputed data set is also discussed. The Canadian Journal of Statistics 48: 138–151; 2020 © 2019 Statistical Society of Canada