Missing data methods for arbitrary missingness with small samples

Missing data are a prevalent and widespread data analytic issue and previous studies have performed simulations to compare the performance of missing data methods in various contexts and for various models; however, one such context that has yet to receive much attention in the literature is the handling of missing data with small samples, particularly when the missingness is arbitrary. Prior studies have either compared methods for small samples with monotone missingness commonly found in longitudinal studies or have investigated the performance of a single method to handle arbitrary missingness with small samples but studies have yet to compare the relative performance of commonly implemented missing data methods for small samples with arbitrary missingness. This study conducts a simulation study to compare and assess the small sample performance of maximum likelihood, listwise deletion, joint multiple imputation, and fully conditional specification multiple imputation for a single-level regression model with a continuous outcome. Results showed that, provided assumptions are met, joint multiple imputation unanimously performed best of the methods examined in the conditions under study.     

A multiple imputation method for incomplete correlated ordinal data using multivariate probit models

The multiple imputation technique has proven to be a useful tool in missing data analysis. We propose a Markov chain Monte Carlo method to conduct multiple imputation for incomplete correlated ordinal data using the multivariate probit model. We conduct a thorough simulation study to compare the performance of our proposed method with two available imputation methods – multivariate normal-based and chain equation methods for various missing data scenarios. For illustration, we present an application using the data from the smoking cessation treatment study for low-income community corrections smokers.     

MIMCA: multiple imputation for categorical variables with multiple correspondence analysis

We propose a multiple imputation method to deal with incomplete categorical data. This method imputes the missing entries using the principal component method dedicated to categorical data: multiple correspondence analysis (MCA). The uncertainty concerning the parameters of the imputation model is reflected using a non-parametric bootstrap. Multiple imputation using MCA (MIMCA) requires estimating a small number of parameters due to the dimensionality reduction property of MCA. It allows the user to impute a large range of data sets. In particular, a high number of categories per variable, a high number of variables or a small number of individuals are not an issue for MIMCA. Through a simulation study based on real data sets, the method is assessed and compared to the reference methods (multiple imputation using the loglinear model, multiple imputation by logistic regressions) as well to the latest works on the topic (multiple imputation by random forests or by the Dirichlet process mixture of products of multinomial distributions model). The proposed method provides a good point estimate of the parameters of the analysis model considered, such as the coefficients of a main effects logistic regression model, and a reliable estimate of the variability of the estimators. In addition, MIMCA has the great advantage that it is substantially less time consuming on data sets of high dimensions than the other multiple imputation methods.     

Efficient ways to impute incomplete panel data

We find that existing multiple imputation procedures that are currently implemented in major statistical packages and that are available to the wide majority of data analysts are limited with regard to handling incomplete panel data. We review various missing data methods that we deem useful for the analysis of incomplete panel data and discuss, how some of the shortcomings of existing procedures can be overcome. In a simulation study based on real panel data, we illustrate these procedures’ quality and outline fruitful avenues of future research.     

An Empirical Comparison of Multiple Imputation Methods for Categorical Data

Multiple imputation is a common approach for dealing with missing values in statistical databases. The imputer fills in missing values with draws from predictive models estimated from the observed data, resulting in multiple, completed versions of the database. Researchers have developed a variety of default routines to implement multiple imputation; however, there has been limited research comparing the performance of these methods, particularly for categorical data. We use simulation studies to compare repeated sampling properties of three default multiple imputation methods for categorical data, including chained equations using generalized linear models, chained equations using classification and regression trees, and a fully Bayesian joint distribution based on Dirichlet process mixture models. We base the simulations on categorical data from the American Community Survey. In the circumstances of this study, the results suggest that default chained equations approaches based on generalized linear models are dominated by the default regression tree and Bayesian mixture model approaches. They also suggest competing advantages for the regression tree and Bayesian mixture model approaches, making both reasonable default engines for multiple imputation of categorical data. Supplementary material for this article is available online.     

Multiple imputation of missing data with ante-dependence covariance structure

A controlled clinical trial was conducted to investigate the efficacy effect of a chemical compound in the treatment of Premenstrual Dysphoric Disorder (PMDD). The data from the trial showed a non-monotone pattern of missing data and an ante-dependence covariance structure. A new analytical method for imputing the missing data with the ante-dependence covariance is proposed. The PMDD data are analysed by the non-imputation method and two imputation methods: the proposed method and the MCMC method.     

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).     

Multiple imputation compared with restricted pseudo‐likelihood and generalized estimating equations for analysis of binary repeated measures in clinical studies

Non‐likelihood‐based methods for repeated measures analysis of binary data in clinical trials can result in biased estimates of treatment effects and associated standard errors when the dropout process is not completely at random. We tested the utility of a multiple imputation approach in reducing these biases. Simulations were used to compare performance of multiple imputation with generalized estimating equations and restricted pseudo‐likelihood in five representative clinical trial profiles for estimating (a) overall treatment effects and (b) treatment differences at the last scheduled visit. In clinical trials with moderate to high (40–60%) dropout rates with dropouts missing at random, multiple imputation led to less biased and more precise estimates of treatment differences for binary outcomes based on underlying continuous scores. Copyright © 2005 John Wiley & Sons, Ltd.     

Use of multiple imputation in supersampled nested case-control and case-cohort studies

Nested case-control and case-cohort studies are useful for studying associations between covariates and time-to-event when some covariates are expensive to measure. Full covariate information is collected in the nested case-control or case-cohort sample only, while cheaply measured covariates are often observed for the full cohort. Standard analysis of such case-control samples ignores any full cohort data. Previous work has shown how data for the full cohort can be used efficiently by multiple imputation of the expensive covariate(s), followed by a full-cohort analysis. For large cohorts this is computationally expensive or even infeasible. An alternative is to supplement the case-control samples with additional controls on which cheaply measured covariates are observed. We show how multiple imputation can be used for analysis of such supersampled data. Simulations show that this brings efficiency gains relative to a traditional analysis and that the efficiency loss relative to using the full cohort data is not substantial.     

Tukey's gh Distribution for Multiple Imputation

Tukey proposed a class of distributions, the g-and-h family (gh family), based on a transformation of a standard normal variable to accommodate different skewness and elongation in the distribution of variables arising in practical applications. It is easy to draw values from this distribution even though it is hard to explicitly state the probability density function. Given this flexibility, the gh family may be extremely useful in creating multiple imputations for missing data. This article demonstrates how this family, as well as its generalizations, can be used in the multiple imputation analysis of incomplete data. The focus of this article is on a scalar variable with missing values. In the absence of any additional information, data are missing completely at random, and hence the correct analysis is the complete-case analysis. Thus, the application of the gh multiple imputation to the scalar cases affords comparison with the correct analysis and with other model-based multiple imputation methods. Comparisons are made using simulated datasets and the data from a survey of adolescents ascertaining driving after drinking alcohol.     

Different methods for handling incomplete longitudinal binary outcome due to missing at random dropout

This paper compares the performance of weighted generalized estimating equations (WGEEs), multiple imputation based on generalized estimating equations (MI-GEEs) and generalized linear mixed models (GLMMs) for analyzing incomplete longitudinal binary data when the underlying study is subject to dropout. The paper aims to explore the performance of the above methods in terms of handling dropouts that are missing at random (MAR). The methods are compared on simulated data. The longitudinal binary data are generated from a logistic regression model, under different sample sizes. The incomplete data are created for three different dropout rates. The methods are evaluated in terms of bias, precision and mean square error in case where data are subject to MAR dropout. In conclusion, across the simulations performed, the MI-GEE method performed better in both small and large sample sizes. Evidently, this should not be seen as formal and definitive proof, but adds to the body of knowledge about the methods’ relative performance. In addition, the methods are compared using data from a randomized clinical trial.     

A test of the missing data mechanism for repeated measures data

The occurrence of missing data is an often unavoidable consequence of repeated measures studies. Fortunately, multivariate general linear models such as growth curve models and linear mixed models with random effects have been well developed to analyze incomplete normally-distributed repeated measures data. Most statistical methods have assumed that the missing data occur at random. This assumption may include two types of missing data mechanism: missing completely at random (MCAR) and missing at random (MAR) in the sense of Rubin (1976). In this paper, we develop a test procedure for distinguishing these two types of missing data mechanism for incomplete normally-distributed repeated measures data. The proposed test is similar in spiril to the test of Park and Davis (1992). We derive the test for incomplete normally-distribrlted repeated measures data using linear mixed models. while Park and Davis (1992) cleirved thr test for incomplete repeatctl categorical data in the framework of Grizzle Starmer. and Koch (1969). Thr proposed procedure can be applied easily to any other multivariate general linear model which allow for missing data. The test is illustrated using the hip-replacernent patient.data from Crowder and Hand (1990).     

Multiple imputation methods for recurrent event data with missing event category

Frequently in clinical and epidemiologic studies, the event of interest is recurrent (i.e., can occur more than once per subject). When the events are not of the same type, an analysis which accounts for the fact that events fall into different categories will often be more informative. Often, however, although event times may always be known, information through which events are categorized may potentially be missing. Complete‐case methods (whose application may require, for example, that events be censored when their category cannot be determined) are valid only when event categories are missing completely at random. This assumption is rather restrictive. The authors propose two multiple imputation methods for analyzing multiple‐category recurrent event data under the proportional means/rates model. The use of a proper or improper imputation technique distinguishes the two approaches. Both methods lead to consistent estimation of regression parameters even when the missingness of event categories depends on covariates. The authors derive the asymptotic properties of the estimators and examine their behaviour in finite samples through simulation. They illustrate their approach using data from an international study on dialysis.     

Practical Advice on How to Impute Continuous Data When the Ultimate Interest Centers on Dichotomized Outcomes Through Pre-Specified Thresholds

Multiple imputation under the multivariate normality assumption has often been regarded as a viable model-based approach in dealing with incomplete continuous data in the last two decades. A situation where the measurements are taken on a continuous scale with an ultimate interest in dichotomized versions through discipline-specific thresholds is not uncommon in applied research, especially in medical and social sciences. In practice, researchers generally tend to impute missing values for continuous outcomes under a Gaussian imputation model, and then dichotomize them via commonly-accepted cut-off points. An alternative strategy is creating multiply imputed data sets after dichotomization under a log-linear imputation model that uses a saturated multinomial structure. In this work, the performances of the two imputation methods were examined on a fairly wide range of simulated incomplete data sets that exhibit varying distributional characteristics such as skewness and multimodality. Behavior of efficiency and accuracy measures was explored to determine the extent to which the procedures work properly. The conclusion drawn is that dichotomization before carrying out a log-linear imputation should be the preferred approach except for a few special cases. I recommend that researchers use the atypical second strategy whenever the interest centers on binary quantities that are obtained through underlying continuous measurements. A possible explanation is that erratic/idiosyncratic aspects that are not accommodated by a Gaussian model are probably transformed into better-behaving discrete trends in this particular missing-data setting. This premise outweighs the assertion that continuous variables inherently carry more information, leading to a counter-intuitive, but potentially useful result for practitioners.     

Bias of factor loadings from questionnaire data with imputed scores

This study investigated the bias of factor loadings obtained from incomplete questionnaire data with imputed scores. Three models were used to generate discrete ordered rating scale data typical of questionnaires, also known as Likert data. These methods were the multidimensional polytomous latent trait model, a normal ogive item response theory model, and the discretized normal model. Incomplete data due to nonresponse were simulated using either missing completely at random or not missing at random mechanisms. Subsequently, for each incomplete data matrix, four imputation methods were applied for imputing item scores. Based on a completely crossed six-factor design, it was concluded that in general, bias was small for all data simulation methods and all imputation methods, and under all nonresponse mechanisms. Imputation method, two-way-plus-error, had the smallest bias in the factor loadings. Bias based on the discretized normal model was greater than that based on the other two models.     

Imputation techniques for incomplete data in quadratic discriminant analysis

We have compared the efficacy of five imputation algorithms readily available in SAS for the quadratic discriminant function. Here, we have generated several different parametric-configuration training data with missing data, including monotone missing-at-random observations, and used a Monte Carlo simulation to examine the expected probabilities of misclassification for the two-class quadratic statistical discrimination problem under five different imputation methods. Specifically, we have compared the efficacy of the complete observation-only method and the mean substitution, regression, predictive mean matching, propensity score, and Markov Chain Monte Carlo (MCMC) imputation methods. We found that the MCMC and propensity score multiple imputation approaches are, in general, superior to the other imputation methods for the configurations and training-sample sizes we considered.     

Latent class based multiple imputation approach for missing categorical data

In this paper we propose a latent class based multiple imputation approach for analyzing missing categorical covariate data in a highly stratified data model. In this approach, we impute the missing data assuming a latent class imputation model and we use likelihood methods to analyze the imputed data. Via extensive simulations, we study its statistical properties and make comparisons with complete case analysis, multiple imputation, saturated log-linear multiple imputation and the Expectation–Maximization approach under seven missing data mechanisms (including missing completely at random, missing at random and not missing at random). These methods are compared with respect to bias, asymptotic standard error, type I error, and 95% coverage probabilities of parameter estimates. Simulations show that, under many missingness scenarios, latent class multiple imputation performs favorably when jointly considering these criteria. A data example from a matched case–control study of the association between multiple myeloma and polymorphisms of the Inter-Leukin 6 genes is considered.     

A new multivariate imputation method based on Bayesian networks

Dealing with incomplete data is a pervasive problem in statistical surveys. Bayesian networks have been recently used in missing data imputation. In this research, we propose a new methodology for the multivariate imputation of missing data using discrete Bayesian networks and conditional Gaussian Bayesian networks. Results from imputing missing values in coronary artery disease data set and milk composition data set as well as a simulation study from cancer-neapolitan network are presented to demonstrate and compare the performance of three Bayesian network-based imputation methods with those of multivariate imputation by chained equations (MICE) and the classical hot-deck imputation method. To assess the effect of the structure learning algorithm on the performance of the Bayesian network-based methods, two methods called Peter-Clark algorithm and greedy search-and-score have been applied. Bayesian network-based methods are: first, the method introduced by Di Zio et al. [Bayesian networks for imputation, J. R. Stat. Soc. Ser. A 167 (2004), 309–322] in which, each missing item of a variable is imputed using the information given in the parents of that variable; second, the method of Di Zio et al. [Multivariate techniques for imputation based on Bayesian networks, Neural Netw. World 15 (2005), 303–310] which uses the information in the Markov blanket set of the variable to be imputed and finally, our new proposed method which applies the whole available knowledge of all variables of interest, consisting the Markov blanket and so the parent set, to impute a missing item. Results indicate the high quality of our new proposed method especially in the presence of high missingness percentages and more connected networks. Also the new method have shown to be more efficient than the MICE method for small sample sizes with high missing rates.     

Sensitivity to imputation models and assumptions in receiver operating characteristic analysis with incomplete data

Modern statistical methods using incomplete data have been increasingly applied in a wide variety of substantive problems. Similarly, receiver operating characteristic (ROC) analysis, a method used in evaluating diagnostic tests or biomarkers in medical research, has also been increasingly popular problem in both its development and application. While missing-data methods have been applied in ROC analysis, the impact of model mis-specification and/or assumptions (e.g. missing at random) underlying the missing data has not been thoroughly studied. In this work, we study the performance of multiple imputation (MI) inference in ROC analysis. Particularly, we investigate parametric and non-parametric techniques for MI inference under common missingness mechanisms. Depending on the coherency of the imputation model with the underlying data generation mechanism, our results show that MI generally leads to well-calibrated inferences under ignorable missingness mechanisms.     

USING LINEAR PREDICTORS TO IMPUTE ALLELE FREQUENCIES FROM SUMMARY OR POOLED GENOTYPE DATA

Recently-developed genotype imputation methods are a powerful tool for detecting untyped genetic variants that affect disease susceptibility in genetic association studies. However, existing imputation methods require individual-level genotype data, whereas in practice it is often the case that only summary data are available. For example this may occur because, for reasons of privacy or politics, only summary data are made available to the research community at large; or because only summary data are collected, as in DNA pooling experiments. In this article, we introduce a new statistical method that can accurately infer the frequencies of untyped genetic variants in these settings, and indeed substantially improve frequency estimates at typed variants in pooling experiments where observations are noisy. Our approach, which predicts each allele frequency using a linear combination of observed frequencies, is statistically straight-forward, and related to a long history of the use of linear methods for estimating missing values (e.g. Kriging). The main statistical novelty is our approach to regularizing the covariance matrix estimates, and the resulting linear predictors, which is based on methods from population genetics. We find that, besides being both fast and flexible - allowing new problems to be tackled that cannot be handled by existing imputation approaches purpose-built for the genetic context - these linear methods are also very accurate. Indeed, imputation accuracy using this approach is similar to that obtained by state-of-the art imputation methods that use individual-level data, but at a fraction of the computational cost.