Estimating the average causal effect (ACE) using observational data is a key focus in causal inference for which missing data present an important challenge. Multiple imputation (MI) is a widely used method for handling missing data and can yield unbiased estimates when the imputation is compatible with the substantive analysis. One of the advantages of MI is its scope to include so-called "auxiliary variables", defined as variables associated with incomplete variables that are excluded from the substantive analysis. Although many studies have looked at the use of auxiliary variables in MI for improving precision, the study of auxiliary variables that are necessary for the identifiability (or "recoverability") of the ACE in the presence of missing data has been scant. In this work, we investigate the use of auxiliary variables, both mediators and non-mediators, across a range of typical univariable and multivariable missingness mechanisms depicted by missingness directed acyclic graphs (m-DAGs). For each setting, we derive recoverability results, then evaluate MI-based and complete-case methods for estimating the ACE using correctly specified g-computation, considering different strategies for incorporating auxiliary variables and varying degrees of compatibility for MI models. Based on findings from the simulation studies, we provide practical guidance, highlighting that distinguishing appropriately between mediator and non-mediator auxiliary variables is important to avoid bias as is the use of compatible and flexible (non-parametric) MI methods that incorporate these variables.
A method using multiple imputation and bootstrap for dealing with missing data in mediation analysis is introduced and implemented in SAS. Through simulation studies, it is shown that the method performs well for both MCAR and MAR data without and with auxiliary variables. It is also shown that the method works equally well for MNAR data if auxiliary variables related to missingness are included. The application of the method is demonstrated through the analysis of a subset of data from the National Longitudinal Survey of Youth.
The problem of missingness in observational data is ubiquitous. When the confounders are missing at random, multiple imputation is commonly used; however, the method requires congeniality conditions for valid inferences, which may not be satisfied when estimating average causal treatment effects. Alternatively, fractional imputation, proposed by Kim 2011, has been implemented to handling missing values in regression context. In this article, we develop fractional imputation methods for estimating the average treatment effects with confounders missing at random. We show that the fractional impu…
Multiple imputation is widely used to handle missing data. Although Rubin's combining rule is simple, it is not clear whether or not the standard multiple imputation inference is consistent when coupled with the commonly-used full sample estimators. This article establishes a unified martingale representation of multiple imputation for a wide class of asymptotically linear full sample estimators. This representation invokes the wild bootstrap inference to provide consistent variance estimation under the correct specification of the imputation models. As a motivating application, we illustrate …
Multiple imputation (MI) is a popular method for handling missing data. Auxiliary variables can be added to the imputation model(s) to improve MI estimates. However, the choice of which auxiliary variables to include in the imputation model is not always straightforward. Including too few may lead to important information being discarded, but including too many can cause problems with convergence of the estimation procedures for imputation models. Several data-driven auxiliary variable selection strategies have been proposed. This paper uses a simulation study and a case study to provide a com…
Imputation models sometimes use auxiliary variables that, though not part of the planned analysis, can improve the accuracy of imputed values and the efficiency of point estimates. A recent article, using evidence from simulations, argued that the use of auxiliary variables in imputation did not improve efficiency. We review the simulation results and find that the use of auxiliary variables did improve efficiency; under some conditions the efficiency gain was equivalent to increasing the sample size by a quarter. We give an example from our own research where the efficiency gained from auxili…
Multiple imputation is a well-established general technique for analyzing data with missing values. A convenient way to implement multiple imputation is sequential regression multiple imputation (SRMI), also called chained equations multiple imputation. In this approach, we impute missing values using regression models for each variable, conditional on the other variables in the data. This approach, however, assumes that the missingness mechanism is missing at random, and it is not well-justified under not-at-random missingness without additional modification. In this paper, we describe how we…
This article introduces the Python package gcimpute for missing data imputation. gcimpute can impute missing data with many different variable types, including continuous, binary, ordinal, count, and truncated values, by modeling data as samples from a Gaussian copula model. This semiparametric model learns the marginal distribution of each variable to match the empirical distribution, yet describes the interactions between variables with a joint Gaussian that enables fast inference, imputation with confidence intervals, and multiple imputation. The package also provides specialized extensions…
Item nonresponse is frequently encountered in practice. Ignoring missing data can lose efficiency and lead to misleading inference. Fractional imputation is a frequentist approach of imputation for handling missing data. However, the parametric fractional imputation of \cite{kim2011parametric} may be subject to bias under model misspecification. In this paper, we propose a novel semiparametric fractional imputation method using Gaussian mixture models. The proposed method is computationally efficient and leads to robust estimation. The proposed method is further extended to incorporate the cat…
Return-to-baseline is an important method to impute missing values or unobserved potential outcomes when certain hypothetical strategies are used to handle intercurrent events in clinical trials. Current return-to-baseline approaches seen in literature and in practice inflate the variability of the "complete" dataset after imputation and lead to biased mean estimators {when the probability of missingness depends on the observed baseline and/or postbaseline intermediate outcomes}. In this article, we first provide a set of criteria a return-to-baseline imputation method should satisfy. Under th…
This paper presents a new methodology to solve problems resulting from missing data in large-scale item performance behavioral databases. Useful statistics corrected for missing data are described, and a new method of imputation for missing data is proposed. This methodology is applied to the DLP database recently published by Keuleers et al. (2010), which allows us to conclude that this database fulfills the conditions of use of the method recently proposed by Courrieu et al. (2011) to test item performance models. Two application programs in Matlab code are provided for the imputation of mis…
Background: Existing guidelines for handling missing data are generally not consistent with the goals of prediction modelling, where missing data can occur at any stage of the model pipeline. Multiple imputation (MI), often heralded as the gold standard approach, can be challenging to apply in the clinic. Clearly, the outcome cannot be used to impute data at prediction time. Regression imputation (RI) may offer a pragmatic alternative in the prediction context, that is simpler to apply in the clinic. Moreover, the use of missing indicators can handle informative missingness, but it is currentl…
Missing data theory deals with the statistical methods in the occurrence of missing data. Missing data occurs when some values are not stored or observed for variables of interest. However, most of the statistical theory assumes that data is fully observed. An alternative to deal with incomplete databases is to fill in the spaces corresponding to the missing information based on some criteria, this technique is called imputation. We introduce a new imputation methodology for databases with univariate missing patterns based on additional information from fully-observed auxiliary variables. We a…
Objective: Researchers often use model-based multiple imputation to handle missing at random data to minimize bias while making the best use of all available data. However, there are sometimes constraints within the data that make model-based imputation difficult and may result in implausible values. In these contexts, we describe how to use random hot deck imputation to allow for plausible multiple imputation in longitudinal studies. Study Design and Setting: We illustrate random hot deck multiple imputation using The Childhood Health, Activity, and Motor Performance School Study Denmark (CHA…
We outline a framework for multiple imputation of nonignorable item nonresponse when the marginal distributions of some of the variables with missing values are known. In particular, our framework ensures that (i) the completed datasets result in design-based estimates of totals that are plausible, given the margins, and (ii) the completed datasets maintain associations across variables as posited in the imputation models. To do so, we propose an additive nonignorable model for nonresponse, coupled with a rejection sampling step. The rejection sampling step favors completed datasets that resul…
Not-at-random missingness presents a challenge in addressing missing data in many health research applications. In this paper, we propose a new approach to account for not-at-random missingness after multiple imputation through weighted analysis of stacked multiple imputations. The weights are easily calculated as a function of the imputed data and assumptions about the not-at-random missingness. We demonstrate through simulation that the proposed method has excellent performance when the missingness model is correctly specified. In practice, the missingness mechanism will not be known. We sho…
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…
We present an approach for imputation of missing items in multivariate categorical data nested within households. The approach relies on a latent class model that (i) allows for household level and individual level variables, (ii) ensures that impossible household configurations have zero probability in the model, and (iii) can preserve multivariate distributions both within households and across households. We present a Gibbs sampler for estimating the model and generating imputations. We also describe strategies for improving the computational efficiency of the model estimation. We illustrat…
Many real-world datasets contain missing entries and mixed data types including categorical and ordered (e.g. continuous and ordinal) variables. Imputing the missing entries is necessary, since many data analysis pipelines require complete data, but this is challenging especially for mixed data. This paper proposes a probabilistic imputation method using an extended Gaussian copula model that supports both single and multiple imputation. The method models mixed categorical and ordered data using a latent Gaussian distribution. The unordered characteristics of categorical variables is explicitl…
Many imputation methods are based on statistical models that assume that the variable of interest is a noisy observation of a function of the auxiliary variables or covariates. Misspecification of this model may lead to severe errors in estimates and to misleading conclusions. A new imputation method for item nonresponse in surveys is proposed based on a nonparametric estimation of the functional dependence between the variable of interest and the auxiliary variables. We consider the use of smoothing spline estimation within an additive model framework to flexibly build an imputation model in …
Missing data imputation forms the first critical step of many data analysis pipelines. The challenge is greatest for mixed data sets, including real, Boolean, and ordinal data, where standard techniques for imputation fail basic sanity checks: for example, the imputed values may not follow the same distributions as the data. This paper proposes a new semiparametric algorithm to impute missing values, with no tuning parameters. The algorithm models mixed data as a Gaussian copula. This model can fit arbitrary marginals for continuous variables and can handle ordinal variables with many levels, …
Electronic health records (EHRs) are increasingly used for clinical and comparative effectiveness research, but suffer from missing data. Motivated by health services research on diabetes care, we seek to increase the quality of EHRs by focusing on missing values of longitudinal glycosylated hemoglobin (A1c), a key risk factor for diabetes complications and adverse events. Under the framework of multiple imputation (MI), we propose an individualized Bayesian latent profiling approach to capture A1c measurement trajectories subject to missingness. The proposed method is applied to EHRs of adult…
Missing observations are common in cluster randomised trials. Approaches taken to handling such missing data include: complete case analysis, single-level multiple imputation that ignores the clustering, multiple imputation with a fixed effect for each cluster and multilevel multiple imputation. We conducted a simulation study to assess the performance of these approaches, in terms of confidence interval coverage and empirical bias in the estimated treatment effects. Missing-at-random clustered data scenarios were simulated following a full-factorial design. An Analysis of Variance was carried…
We propose a copula based method to handle missing values in multivariate data of mixed types in multilevel data sets. Building upon the extended rank likelihood of \cite{hoff2007extending} and the multinomial probit model, our model is a latent variable model which is able to capture the relationship among variables of different types as well as accounting for the clustering structure. We fit the model by approximating the posterior distribution of the parameters and the missing values through a Gibbs sampling scheme. We use the multiple imputation procedure to incorporate the uncertainty due…
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…
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…
Missing data is a common problem in medical research, and is commonly addressed using multiple imputation. Although traditional imputation methods allow for valid statistical inference when data are missing at random (MAR), their implementation is problematic when the presence of missingness depends on unobserved variables, i.e. the data are missing not at random (MNAR). Unfortunately, this MNAR situation is rather common, in observational studies, registries and other sources of real-world data. While several imputation methods have been proposed for addressing individual studies when data ar…
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…
Missing data are frequently encountered in high-dimensional problems, but they are usually difficult to deal with using standard algorithms, such as the expectation-maximization (EM) algorithm and its variants. To tackle this difficulty, some problem-specific algorithms have been developed in the literature, but there still lacks a general algorithm. This work is to fill the gap: we propose a general algorithm for high-dimensional missing data problems. The proposed algorithm works by iterating between an imputation step and a consistency step. At the imputation step, the missing data are impu…
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…
This paper presents an impact assessment for the imputation of missing data. The data set used is HIV Seroprevalence data from an antenatal clinic study survey performed in 2001. Data imputation is performed through five methods: Random Forests, Autoassociative Neural Networks with Genetic Algorithms, Autoassociative Neuro-Fuzzy configurations, and two Random Forest and Neural Network based hybrids. Results indicate that Random Forests are superior in imputing missing data in terms both of accuracy and of computation time, with accuracy increases of up to 32% on average for certain variables w…
Missing data are ubiquitous in the era of big data and, if inadequately handled, are known to lead to biased findings and have deleterious impact on data-driven decision makings. To mitigate its impact, many missing value imputation methods have been developed. However, the fairness of these imputation methods across sensitive groups has not been studied. In this paper, we conduct the first known research on fairness of missing data imputation. By studying the performance of imputation methods in three commonly used datasets, we demonstrate that unfairness of missing value imputation widely ex…
Clinical decision support using data mining techniques offers more intelligent way to reduce the decision error in the last few years. However, clinical datasets often suffer from high missingness, which adversely impacts the quality of modelling if handled improperly. Imputing missing values provides an opportunity to resolve the issue. Conventional imputation methods adopt simple statistical analysis, such as mean imputation or discarding missing cases, which have many limitations and thus degrade the performance of learning. This study examines a series of machine learning based imputation …
Missing data is a common problem which has consistently plagued statisticians and applied analytical researchers. While replacement methods like mean-based or hot deck imputation have been well researched, emerging imputation techniques enabled through improved computational resources have had limited formal assessment. This study formally considers five more recently developed imputation methods: Amelia, Mice, mi, Hmisc and missForest - compares their performances using RMSE against actual values and against the well-established mean-based replacement approach. The RMSE measure was consolidat…
Imputation of missing data is a common application in various classification problems where the feature training matrix has missingness. A widely used solution to this imputation problem is based on the lazy learning technique, $k$-nearest neighbor (kNN) approach. However, most of the previous work on missing data does not take into account the presence of the class label in the classification problem. Also, existing kNN imputation methods use variants of Minkowski distance as a measure of distance, which does not work well with heterogeneous data. In this paper, we propose a novel iterative k…
Multiple imputation (MI) is an established technique to handle missing data in observational studies. Joint modeling (JM) and fully conditional specification (FCS) are commonly used methods for imputing multilevel clustered data. However, MI approaches for ordinal clustered outcome variables have not been well studied, especially when there is informative cluster size (ICS). The purpose of this study is to describe different imputation and analysis strategies for the multilevel ordinal outcome when ICS exists. We conducted comprehensive Monte Carlo simulation studies to compare five different …
Although approaches for handling missing data from longitudinal studies are well-developed when the patterns of missingness are monotone, fewer methods are available for non-monotone missingness. Moreover, the conventional missing at random (MAR) assumption -- a natural benchmark for monotone missingness -- does not model realistic beliefs about non-monotone missingness processes (Robins and Gill, 1997). This has provided the impetus for alternative non-monotone missing not at random (MNAR) mechanisms. The "no self-censoring" (NSC) model is such a mechanism and assumes the probability an outco…
Missing data are ubiquitous in real world applications and, if not adequately handled, may lead to the loss of information and biased findings in downstream analysis. Particularly, high-dimensional incomplete data with a moderate sample size, such as analysis of multi-omics data, present daunting challenges. Imputation is arguably the most popular method for handling missing data, though existing imputation methods have a number of limitations. Single imputation methods such as matrix completion methods do not adequately account for imputation uncertainty and hence would yield improper statist…
Genomic data arising from a genome-wide association study (GWAS) are often not only of large-scale, but also incomplete. A specific form of their incompleteness is missing values with non-ignorable missingness mechanism. The intrinsic complications of genomic data present significant challenges in developing an unbiased and informative procedure of phenotype-genotype association analysis by a statistical variable selection approach. In this paper we develop a coherent procedure of categorical phenotype-genotype association analysis, in the presence of missing values with non-ignorable missingn…
Missing data on response variables are common in clinical studies. Corresponding to the uncertainty of missing mechanism, theoretical frameworks on controlled imputation have been developed. In practice, it is recommended to conduct a statistically valid analysis under the primary assumptions on missing data, followed by sensitivity analysis under alternative assumptions to assess the robustness of results. Due to the availability of software, controlled multiple imputation (MI) procedures, including delta-based and reference-based approaches, have become popular for analyzing continuous varia…
Gary and Mary West Health Institute（加里与玛丽·韦斯特健康研究所）
Although data may be abundant, complete data is less so, due to missing columns or rows. This missingness undermines the performance of downstream data products that either omit incomplete cases or create derived completed data for subsequent processing. Appropriately managing missing data is required in order to fully exploit and correctly use data. We propose a Multiple Imputation model using Denoising Autoencoders to learn the internal representation of data. Furthermore, we use the novel mechanisms of Metamorphic Truth and Imputation Feedback to maintain statistical integrity of attributes…
