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 sample from the posterior distribution. In addition, the Bayesian model comparison criteria, the modified Deviance Information Criterion (mDIC) and the modified Logarithm of the Pseudo-Marginal Likelihood (mLPML), are developed to assess the fit of spatial regression models for spatial data. Extensive simulation studies are carried out to examine empirical performance of the proposed methods. We further apply the proposed methodology to analyze a real data set from a Chinese Health and Nutrition Survey (CHNS) conducted in 2011.
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…
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…
Missing values in covariates due to censoring by signal interference or lack of sensitivity in the measuring devices are common in industrial problems. We propose a full Bayesian solution to the prediction problem with an efficient Markov Chain Monte Carlo (MCMC) algorithm that updates all the censored covariate values jointly in a random scan Gibbs sampler. We show that the joint updating of missing covariate values can be at least two orders of magnitude more efficient than univariate updating. This increased efficiency is shown to be crucial for quickly learning the missing covariate values…
An important task in drug development is to identify patients, which respond better or worse to an experimental treatment. Identifying predictive covariates, which influence the treatment effect and can be used to define subgroups of patients, is a key aspect of this task. Analyses of treatment effect heterogeneity are however known to be challenging, since the number of possible covariates or subgroups is often large, while samples sizes in earlier phases of drug development are often small. In addition, distinguishing predictive covariates from prognostic covariates, which influence the resp…
MIT CSAIL（麻省理工学院计算机科学与人工智能实验室）；Broad Institute（博德研究所）
Hierarchical Bayesian methods enable information sharing across multiple related regression problems. While standard practice is to model regression parameters (effects) as (1) exchangeable across datasets and (2) correlated to differing degrees across covariates, we show that this approach exhibits poor statistical performance when the number of covariates exceeds the number of datasets. For instance, in statistical genetics, we might regress dozens of traits (defining datasets) for thousands of individuals (responses) on up to millions of genetic variants (covariates). When an analyst has mo…
In this paper we recast the problem of missing values in the covariates of a regression model as a latent Gaussian Markov random field (GMRF) model in a fully Bayesian framework. Our proposed approach is based on the definition of the covariate imputation sub-model as a latent effect with a GMRF structure. We show how this formulation works for continuous covariates and provide some insight on how this could be extended to categorical covariates. The resulting Bayesian hierarchical model naturally fits within the integrated nested Laplace approximation (INLA) framework, which we use for model …
Aalto University（阿尔托大学）；University of Helsinki（赫尔辛基大学）；Bayer Pharmaceuticals（拜耳制药）
Conditional variational autoencoders (CVAEs) are versatile deep generative models that extend the standard VAE framework by conditioning the generative model with auxiliary covariates. The original CVAE model assumes that the data samples are independent, whereas more recent conditional VAE models, such as the Gaussian process (GP) prior VAEs, can account for complex correlation structures across all data samples. While several methods have been proposed to learn standard VAEs from partially observed datasets, these methods fall short for conditional VAEs. In this work, we propose a method to …
We introduce Bayesian hierarchical models for predicting high-dimensional tabular survey data which can be distributed from one or multiple classes of distributions (e.g., Gaussian, Poisson, Binomial, etc.). We adopt a Bayesian implementation of a Hierarchical Generalized Transformation (HGT) model to deal with the non-conjugacy of non-Gaussian data models when estimated using a Latent Gaussian Process (LGP) model. Survey data are usually prone to a high degree of sampling error, and we use covariates that are prone to measurement error as well as those free of any such error. A classical meas…
Gaussian graphical models typically assume a homogeneous structure across all subjects, which is often restrictive in applications. In this article, we propose a weighted pseudo-likelihood approach for graphical modeling which allows different subjects to have different graphical structures depending on extraneous covariates. The pseudo-likelihood approach replaces the joint distribution by a product of the conditional distributions of each variable. We cast the conditional distribution as a heteroscedastic regression problem, with covariate-dependent variance terms, to enable information borr…
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 …
We investigate use of two or more linked registers, or lists, for both population size estimation and to investigate the relationship between variables appearing on all or only some registers. This relationship is usually not fully known because some individuals appear in only some registers, and some are not in any register. These two problems have been solved simultaneously using the EM algorithm. We extend this approach to estimate the size of the indigenous Māori population in New Zealand, leading to several innovations: (1) the approach is extended to four registers (including the populat…
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…
We consider the problem of variable selection in high-dimensional settings with missing observations among the covariates. To address this relatively understudied problem, we propose a new synergistic procedure -- adaptive Bayesian SLOPE -- which effectively combines the SLOPE method (sorted $l_1$ regularization) together with the Spike-and-Slab LASSO method. We position our approach within a Bayesian framework which allows for simultaneous variable selection and parameter estimation, despite the missing values. As with the Spike-and-Slab LASSO, the coefficients are regarded as arising from a …
In this dissertation, we develop nonparametric Bayesian models for biomedical data analysis. In particular, we focus on inference for tumor heterogeneity and inference for missing data. First, we present a Bayesian feature allocation model for tumor subclone reconstruction using mutation pairs. The key innovation lies in the use of short reads mapped to pairs of proximal single nucleotide variants (SNVs). In contrast, most existing methods use only marginal reads for unpaired SNVs. In the same context of using mutation pairs, in order to recover the phylogenetic relationship of subclones, we t…
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…
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…
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-kn…
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…
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…
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…
Tuberculosis poses a global health risk and Brazil is among the top twenty countries by absolute mortality. However, this epidemiological burden is masked by under-reporting, which impairs planning for effective intervention. We present a comprehensive investigation and application of a Bayesian hierarchical approach to modelling and correcting under-reporting in tuberculosis counts, a general problem arising in observational count data. The framework is applicable to fully under-reported data, relying only on an informative prior distribution for the mean reporting rate to supplement the part…
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…
