This paper deals with robust marginal estimation under a general regression model when missing data occur in the response and also in some of covariates. The target is a marginal location parameter which is given through an $M-$functional. To obtain robust Fisher--consistent estimators, properly defined marginal distribution function estimators are considered. These estimators avoid the bias due to missing values by assuming a missing at random condition. Three methods are considered to estimate the marginal distribution function which allows to obtain the $M-$location of interest: the well-known inverse probability weighting, a convolution--based method that makes use of the regression model and an augmented inverse probability weighting procedure that prevents against misspecification. The robust proposed estimators and the classical ones are compared through a numerical study under different missing models including clean and contaminated samples. We illustrate the estimators behaviour under a nonlinear model. A real data set is also analysed.
We study problems with multiple missing covariates and partially observed responses. We develop a new framework to handle complex missing covariate scenarios via inverse probability weighting, regression adjustment, and a multiply-robust procedure. We apply our framework to three classical problems: the Cox model from survival analysis, missing response, and binary treatment from causal inference. We also discuss how to handle missing covariates in these scenarios, and develop associated identifying theories and asymptotic theories. We apply our procedure to simulations and an Alzheimer's dise…
Attrition is a common occurrence in cluster randomised trials (CRTs) which leads to missing outcome data. Two approaches for analysing such trials are cluster-level analysis and individual-level analysis. This paper compares the performance of unadjusted cluster-level analysis, baseline covariate adjusted cluster-level analysis and linear mixed model (LMM) analysis, under baseline covariate dependent missingness (CDM) in continuous outcomes, in terms of bias, average estimated standard error and coverage probability. The methods of complete case analysis (CCA) and multiple imputation (MI) are …
Missing outcomes are a commonly occurring problem for cluster randomised trials, which can lead to biased and inefficient inference if ignored or handled inappropriately. Two approaches for analysing such trials are cluster-level analysis and individual-level analysis. In this study, we assessed the performance of unadjusted cluster-level analysis, baseline covariate adjusted cluster-level analysis, random effects logistic regression (RELR) and generalised estimating equations (GEE) when binary outcomes are missing under a baseline covariate dependent missingness mechanism. Missing outcomes we…
In this paper, we propose an empirical likelihood-based weighted estimator of regression parameter in quantile regression model with nonignorable missing covariates. The proposed estimator is computationally simple and achieves semiparametric efficiency if the probability of missingness on the fully observed variables is correctly specified. The efficiency gain of the proposed estimator over the complete-case-analysis estimator is quantified theoretically and illustrated via simulation and a real data application.
Advancements in data collection techniques and the heterogeneity of data resources can yield high percentages of missing observations on variables, such as block-wise missing data. Under missing-data scenarios, traditional methods such as the simple average, $k$-nearest neighbor, multiple, and regression imputations may lead to results that are unstable or unable be computed. Motivated by the concept of semi-supervised learning (see, e.g., Zhu and Goldberg, 2009 and Chapelle et al., 2010), we propose a novel approach with which to fill in missing values in covariates that have high missing rat…
We consider the situation of estimating Cox regression in which some covariates are subject to missing, and there exists additional information (including observed event time, censoring indicator and fully observed covariates) which may be predictive of the missing covariates. We propose to use two working regression models: one for predicting the missing covariates and the other for predicting the missing probabilities. For each missing covariate observation, these two working models are used to define a nearest neighbor imputing set. This set is then used to nonparametrically impute covariat…
In this paper, we present three estimators of the ROC curve when missing observations arise among the biomarkers. Two of the procedures assume that we have covariates that allow to estimate the propensity and the estimators are obtained using an inverse probability weighting method or a smoothed version of it. The other one assumes that the covariates are related to the biomarkers through a regression model which enables us to construct convolution--based estimators of the distribution and quantile functions. Consistency results are obtained under mild conditions. Through a numerical study we …
Randomized Controlled Trials (RCTs) are often considered the gold standard for estimating causal effect, but they may lack external validity when the population eligible to the RCT is substantially different from the target population. Having at hand a sample of the target population of interest allows us to generalize the causal effect. Identifying the treatment effect in the target population requires covariates to capture all treatment effect modifiers that are shifted between the two sets. Standard estimators then use either weighting (IPSW), outcome modeling (G-formula), or combine the tw…
A comparative study of augmented inverse propensity weighted estimators using outcome-oriented covariate selection via penalization with outcome-adaptive lasso
In many applications, survey data are collected from different survey centers in different regions. It happens that in some circumstances, response variables are completely observed while the covariates have missing values. In this paper, we propose a joint spatial regression model for the response variable and missing covariates via a sequence of one-dimensional conditional spatial regression models. We further construct a joint spatial model for missing covariate data mechanisms. The properties of the proposed models are examined and a Markov chain Monte Carlo sampling algorithm is used to s…
Multiple imputation (MI) has become one of the main procedures used to treat missing data, but the guidelines from the methodological literature are not easily transferred to multilevel research. For models including random slopes, proper MI can be difficult, especially when the covariate values are partially missing. In the present article, we discuss applications of MI in multilevel random-coefficient models, theoretical challenges posed by slope variation, and the current limitations of standard MI software. Our findings from three simulation studies suggest that (a) MI is able to recover m…
In longitudinal data a response variable is measured over time, or under different conditions, for a cohort of individuals. In many situations all intended measurements are not available which results in missing values. If the missing value is never followed by an observed measurement, this leads to dropout pattern. The missing values could be in the response variable, the covariates or in both. The missingness mechanism is termed non-random when the probability of missingness depends on the missing value and may be on the observed values. In this case the missing values should be considered i…
Handling incomplete outcomes and covariates in cluster-randomized trials: doubly-robust estimation, efficiency considerations, and sensitivity analysis
In this paper, we consider a weighted local linear estimator based on the inverse selection probability for nonparametric regression with missing covariates at random. The asymptotic distribution of the maximal deviation between the estimator and the true regression function is derived and an asymptotically accurate simultaneous confidence band is constructed. The estimator for the regression function is shown to be oracally efficient in the sense that it is uniformly indistinguishable from that when the selection probabilities are known. Finite sample performance is examined via simulation st…
The standard quantile regression model assumes a linear relationship at the quantile of interest and that all variables are observed. We relax these assumptions by considering a partial linear model while allowing for missing linear covariates. To handle the potential bias caused by missing data we propose a weighted objective function using inverse probability weighting. Our work examines estimators using parametric and nonparametric estimates of the missing probability. For variable selection of the linear terms in the presence of missing data we consider a penalized and weighted objective f…
Missing data is a common problem in clinical data collection, which causes difficulty in the statistical analysis of such data. To overcome problems caused by incomplete data, we propose a new imputation method called projective resampling imputation mean estimation (PRIME), which can also address ``the curse of dimensionality" problem in imputation with less information loss. We use various sample sizes, missing-data rates, covariate correlations, and noise levels in simulation studies, and all results show that PRIME outperformes other methods such as iterative least-squares estimation (ILSE…
Covariate-adaptive randomization schemes such as the minimization and stratified permuted blocks are often applied in clinical trials to balance treatment assignments across prognostic factors. The existing theoretical developments on inference after covariate-adaptive randomization are mostly limited to situations where a correct model between the response and covariates can be specified or the randomization method has well-understood properties. Based on stratification with covariate levels utilized in randomization and a further adjusting for covariates not used in randomization, in this ar…
Semi-parametric methods are often used for the estimation of intervention effects on correlated outcomes in cluster-randomized trials (CRTs). When outcomes are missing at random (MAR), Inverse Probability Weighted (IPW) methods incorporating baseline covariates can be used to deal with informative missingness. Also, augmented generalized estimating equations (AUG) correct for imbalance in baseline covariates but need to be extended for MAR outcomes. However, in the presence of interactions between treatment and baseline covariates, neither method alone produces consistent estimates for the mar…
Propensity score methods are an important tool to help reduce confounding in non-experimental studies. Most propensity score methods assume that covariates are measured without error. However, covariates are often measured with error, which leads to biased causal effect estimates if the true underlying covariates are the actual confounders. Although some studies have investigated the impact of a single mismeasured covariate on estimating a causal effect and proposed methods for handling the measurement error, almost no work exists investigating the case where multiple covariates are mismeasure…
This article focuses on measurement error in covariates in regression analyses in which the aim is to estimate the association between one or more covariates and an outcome, adjusting for confounding. Error in covariate measurements, if ignored, results in biased estimates of parameters representing the associations of interest. Studies with variables measured with error can be considered as studies in which the true variable is missing, for either some or all study participants. We make the link between measurement error and missing data and describe methods for correcting for bias due to cov…
We consider estimating the density of a response conditioning on an error-prone covariate. Motivated by two existing kernel density estimators in the absence of covariate measurement error, we propose a method to correct the existing estimators for measurement error. Asymptotic properties of the resultant estimators under different types of measurement error distributions are derived. Moreover, we adjust bandwidths readily available from existing bandwidth selection methods developed for error-free data to obtain bandwidths for the new estimators. Extensive simulation studies are carried out t…
We propose a general Bayesian nonparametric (BNP) approach to causal inference in the point treatment setting. The joint distribution of the observed data (outcome, treatment, and confounders) is modeled using an enriched Dirichlet process. The combination of the observed data model and causal assumptions allows us to identify any type of causal effect - differences, ratios, or quantile effects, either marginally or for subpopulations of interest. The proposed BNP model is well-suited for causal inference problems, as it does not require parametric assumptions about the distribution of confoun…
Researchers regularly perform conditional prediction using imputed values of missing data. However, applications of imputation often lack a firm foundation in statistical theory. This paper originated when we were unable to find analysis substantiating claims that imputation of missing data has good frequentist properties when data are missing at random (MAR). We focused on the use of observed covariates to impute missing covariates when estimating conditional means of the form E(y|x, w). Here y is an outcome whose realizations are always observed, x is a covariate whose realizations are alway…
In clinical trials, there is potential to improve precision and reduce the required sample size by appropriately adjusting for baseline variables in the statistical analysis. This is called covariate adjustment. Despite recommendations by regulatory agencies in favor of covariate adjustment, it remains underutilized leading to inefficient trials. We address two obstacles that make it challenging to use covariate adjustment. A first obstacle is the incompatibility of many covariate adjusted estimators with commonly used boundaries in group sequential designs (GSDs). A second obstacle is the unc…
Double blind randomized controlled trials are traditionally seen as the gold standard for causal inferences as the difference-in-means estimator is an unbiased estimator of the average treatment effect in the experiment. The fact that this estimator is unbiased over all possible randomizations does not, however, mean that any given estimate is close to the true treatment effect. Similarly, while pre-determined covariates will be balanced between treatment and control groups on average, large imbalances may be observed in a given experiment and the researcher may therefore want to condition on …
Missing data is a common problem in clinical data collection, which causes difficulty in the statistical analysis of such data. In this article, we consider the problem under a framework of a semiparametric partially linear model when observations are subject to missingness with complex patterns. If the correct model structure of the additive partially linear model is available, we propose to use a new imputation method called Partial Replacement IMputation Estimation (PRIME), which can overcome problems caused by incomplete data in the partially linear model. Also, we use PRIME in conjunction…
Logistic regression is a common classification method in supervised learning. Surprisingly, there are very few solutions for performing logistic regression with missing values in the covariates. We suggest a complete approach based on a stochastic approximation version of the EM algorithm to do statistical inference with missing values including the estimation of the parameters and their variance, derivation of confidence intervals and a model selection procedure. We also tackle the problem of prediction for new observations (on a test set) with missing covariate data. The methodology is compu…
Measurement error (ME) and missing values in covariates are often unavoidable in disciplines that deal with data, and both problems have separately received considerable attention during the past decades. However, while most researchers are familiar with methods for treating missing data, accounting for ME in covariates of regression models is less common. In addition, ME and missing data are typically treated as two separate problems, despite practical and theoretical similarities. Here, we exploit the fact that missing data in a continuous covariate is an extreme case of classical ME, allowi…
Linear transformation model provides a general framework for analyzing censored survival data with covariates. The proportional hazards and proportional odds models are special cases of the linear transformation model. In biomedical studies, covariates with measurement error may occur in survival data. In this work, we propose a method to obtain estimators of the regression coefficients in the linear transformation model when the covariates are subject to measurement error. In the proposed method, we assume that instrumental variables are available. We develop counting process based estimating…
Complete randomization allows for consistent estimation of the average treatment effect based on the difference in means of the outcomes without strong modeling assumptions on the outcome-generating process. Appropriate use of the pretreatment covariates can further improve the estimation efficiency. However, missingness in covariates is common in experiments and raises an important question: should we adjust for covariates subject to missingness, and if so, how? The unadjusted difference in means is always unbiased. The complete-covariate analysis adjusts for all completely observed covariate…
In this paper, we propose a data-adaptive empirical likelihood-based approach for treatment effect estimation and inference, which overcomes the obstacle of the traditional empirical likelihood-based approaches in the high-dimensional setting by adopting penalized regression and machine learning methods to model the covariate-outcome relationship. In particular, we show that our procedure successfully recovers the true variance of Zhang's treatment effect estimator (Zhang, 2018) by utilizing a data-splitting technique. Our proposed estimator is proved to be asymptotically normal and semiparame…
Two commonly used methods for improving precision and power in clinical trials are stratified randomization and covariate adjustment. However, many trials do not fully capitalize on the combined precision gains from these two methods, which can lead to wasted resources in terms of sample size and trial duration. We derive consistency and asymptotic normality of model-robust estimators that combine these two methods, and show that these estimators can lead to substantial gains in precision and power. Our theorems cover a class of estimators that handle continuous, binary, and time-to-event outc…
Integrative analysis of datasets generated by multiple cohorts is a widely-used approach for increasing sample size, precision of population estimators, and generalizability of analysis results in epidemiological studies. However, often each individual cohort dataset does not have all variables of interest for an integrative analysis collected as a part of an original study. Such cohort-level missingness poses methodological challenges to the integrative analysis since missing variables have traditionally: (1) been removed from the data for complete case analysis; or (2) been completed by miss…
In many applied fields incomplete covariate vectors are commonly encountered. It is well known that this can be problematic when making inference on model parameters, but its impact on prediction performance is less understood. We develop a method based on covariate dependent partition models that seamlessly handles missing covariates while completely avoiding any type of imputation. The method we develop allows in-sample predictions as well as out-of-sample prediction, even if the missing pattern in the new subjects' incomplete covariate vector was not seen in the training data. Any data type…
Two-stage least squares (TSLS) estimators and variants thereof are widely used to infer the effect of an exposure on an outcome using instrumental variables (IVs). They belong to a wider class of two-stage IV estimators, which are based on fitting a conditional mean model for the exposure, and then using the fitted exposure values along with the covariates as predictors in a linear model for the outcome. We show that standard TSLS estimators enjoy greater robustness to model misspecification than more general two-stage estimators. However, by potentially using a wrong exposure model, e.g. when…
We often seek to estimate the causal effect of an exposure on a particular outcome in both randomized and observational settings. One such estimation method is the covariate-adjusted residuals estimator, which was designed for individually or cluster randomized trials. In this manuscript, we study the properties of this estimator and develop a new estimator that utilizes both covariate adjustment and inverse probability weighting We support our theoretical results with a simulation study and an application in an infectious disease setting. The covariate-adjusted residuals estimator is an effic…
Consider a logistic partially linear model, in which the logit of the mean of a binary response is related to a linear function of some covariates and a nonparametric function of other covariates. We derive simple, doubly robust estimators of coefficient for the covariates in the linear component of the partially linear model. Such estimators remain consistent if either a nuisance model is correctly specified for the nonparametric component, or another nuisance model is correctly specified for the means of the covariates of interest given other covariates and the response at a fixed value. In …
Large-sample properties of multiple imputation estimators for parameters of logistic regression with covariates missing at random separately or simultaneously
研究两组分类协变量分别或同时 MAR 时 logistic 回归 MI 估计量的渐近性质，提出修正方差估计，并通过模拟和逢甲夜市调查数据验证其优势。
The Receiver Operating Characteristic (ROC) curve is a useful tool that measures the discriminating power of a continuous variable or the accuracy of a pharmaceutical or medical test to distinguish between two conditions or classes. In certain situations, the practitioner may be able to measure some covariates related to the diagnostic variable which can increase the discriminating power of the ROC curve. To protect against the existence of atypical data among the observations, a procedure to obtain robust estimators for the ROC curve in presence of covariates is introduced. The considered pro…
