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.     

Empirical likelihood confidence intervals under imputation for missing survey data from stratified simple random sampling

Missing observations due to non‐response are commonly encountered in data collected from sample surveys. The focus of this article is on item non‐response which is often handled by filling in (or imputing) missing values using the observed responses (donors). Random imputation (single or fractional) is used within homogeneous imputation classes that are formed on the basis of categorical auxiliary variables observed on all the sampled units. A uniform response rate within classes is assumed, but that rate is allowed to vary across classes. We construct confidence intervals (CIs) for a population parameter that is defined as the solution to a smooth estimating equation with data collected using stratified simple random sampling. The imputation classes are assumed to be formed across strata. Fractional imputation with a fixed number of random draws is used to obtain an imputed estimating function. An empirical likelihood inference method under the fractional imputation is proposed and its asymptotic properties are derived. Two asymptotically correct bootstrap methods are developed for constructing the desired CIs. In a simulation study, the proposed bootstrap methods are shown to outperform traditional bootstrap methods and some non‐bootstrap competitors under various simulation settings. The Canadian Journal of Statistics 47: 281–301; 2019 © 2019 Statistical Society of Canada     

Bayesian analysis of multivariate t linear mixed models with missing responses at random

The multivariate t linear mixed model (MtLMM) has been recently proposed as a robust tool for analysing multivariate longitudinal data with atypical observations. Missing outcomes frequently occur in longitudinal research even in well controlled situations. As a powerful alternative to the traditional expectation maximization based algorithm employing single imputation, we consider a Bayesian analysis of the MtLMM to account for the uncertainties of model parameters and missing outcomes through multiple imputation. An inverse Bayes formulas sampler coupled with Metropolis-within-Gibbs scheme is used to effectively draw the posterior distributions of latent data and model parameters. The techniques for multiple imputation of missing values, estimation of random effects, prediction of future responses, and diagnostics of potential outliers are investigated as well. The proposed methodology is illustrated through a simulation study and an application to AIDS/HIV data.     

Sequential imputation for models with latent variables assuming latent ignorability

Models that involve an outcome variable, covariates, and latent variables are frequently the target for estimation and inference. The presence of missing covariate or outcome data presents a challenge, particularly when missingness depends on the latent variables. This missingness mechanism is called latent ignorable or latent missing at random and is a generalisation of missing at random. Several authors have previously proposed approaches for handling latent ignorable missingness, but these methods rely on prior specification of the joint distribution for the complete data. In practice, specifying the joint distribution can be difficult and/or restrictive. We develop a novel sequential imputation procedure for imputing covariate and outcome data for models with latent variables under latent ignorable missingness. The proposed method does not require a joint model; rather, we use results under a joint model to inform imputation with less restrictive modelling assumptions. We discuss identifiability and convergence‐related issues, and simulation results are presented in several modelling settings. The method is motivated and illustrated by a study of head and neck cancer recurrence. Imputing missing data for models with latent variables under latent‐dependent missingness without specifying a full joint model.     

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.     

A Bezier curve method in interval-censored data

In this paper we propose a Bezier curve method to estimate the survival function and the median survival time in interval-censored data. We compare the proposed estimator with other existing methods such as the parametric method, the single point imputation method, and the nonparametric maximum likelihood estimator through extensive numerical studies, and it is shown that the proposed estimator performs better than others in the sense of mean squared error and mean integrated squared error. An illustrative example based on a real data set is given.     

Using a mixture model for multiple imputation in the presence of outliers: the 'Healthy for life' project

Summary.  We consider the problem of obtaining population-based inference in the presence of missing data and outliers in the context of estimating the prevalence of obesity and body mass index measures from the 'Healthy for life' study. Identifying multiple outliers in a multivariate setting is problematic because of problems such as masking, in which groups of outliers inflate the covariance matrix in a fashion that prevents their identification when included, and swamping, in which outliers skew covariances in a fashion that makes non-outlying observations appear to be outliers. We develop a latent class model that assumes that each observation belongs to one of K unobserved latent classes, with each latent class having a distinct covariance matrix. We consider the latent class covariance matrix with the largest determinant to form an 'outlier class'. By separating the covariance matrix for the outliers from the covariance matrices for the remainder of the data, we avoid the problems of masking and swamping. As did Ghosh-Dastidar and Schafer, we use a multiple-imputation approach, which allows us simultaneously to conduct inference after removing cases that appear to be outliers and to promulgate uncertainty in the outlier status through the model inference. We extend the work of Ghosh-Dastidar and Schafer by embedding the outlier class in a larger mixture model, consider penalized likelihood and posterior predictive distributions to assess model choice and model fit, and develop the model in a fashion to account for the complex sample design. We also consider the repeated sampling properties of the multiple imputation removal of outliers.     

Multiple imputation for competing risks regression with interval-censored data

ABSTRACT

We present here an extension of Pan's multiple imputation approach to Cox regression in the setting of interval-censored competing risks data. The idea is to convert interval-censored data into multiple sets of complete or right-censored data and to use partial likelihood methods to analyse them. The process is iterated, and at each step, the coefficient of interest, its variance–covariance matrix, and the baseline cumulative incidence function are updated from multiple posterior estimates derived from the Fine and Gray sub-distribution hazards regression given augmented data. Through simulation of patients at risks of failure from two causes, and following a prescheduled programme allowing for informative interval-censoring mechanisms, we show that the proposed method results in more accurate coefficient estimates as compared to the simple imputation approach. We have implemented the method in the MIICD R package, available on the CRAN website.     

Strategies for handling missing data in longitudinal studies with questionnaires

Missing data methods, maximum likelihood estimation (MLE) and multiple imputation (MI), for longitudinal questionnaire data were investigated via simulation. Predictive mean matching (PMM) was applied at both item and scale levels, logistic regression at item level and multivariate normal imputation at scale level. We investigated a hybrid approach which is combination of MLE and MI, i.e. scales from the imputed data are eliminated if all underlying items were originally missing. Bias and mean square error (MSE) for parameter estimates were examined. ML seemed to provide occasionally the best results in terms of bias, but hardly ever on MSE. All imputation methods at the scale level and logistic regression at item level hardly ever showed the best performance. The hybrid approach is similar or better than its original MI. The PMM-hybrid approach at item level demonstrated the best MSE for most settings and in some cases also the smallest bias.     

Robust skew-<Emphasis Type="Italic">t</Emphasis> factor analysis models for handling missing data

This paper presents a novel framework for maximum likelihood (ML) estimation in skew-t factor analysis (STFA) models in the presence of missing values or nonresponses. As a robust extension of the ordinary factor analysis model, the STFA model assumes a restricted version of the multivariate skew-t distribution for the latent factors and the unobservable errors to accommodate non-normal features such as asymmetry and heavy tails or outliers. An EM-type algorithm is developed to carry out ML estimation and imputation of missing values under a missing at random mechanism. The practical utility of the proposed methodology is illustrated through real and synthetic data examples.     

A structured approach to choosing estimands and estimators in longitudinal clinical trials

An important evolution in the missing data arena has been the recognition of need for clarity in objectives. The objectives of primary focus in clinical trials can often be categorized as assessing efficacy or effectiveness. The present investigation illustrated a structured framework for choosing estimands and estimators when testing investigational drugs to treat the symptoms of chronic illnesses. Key issues were discussed and illustrated using a reanalysis of the confirmatory trials from a new drug application in depression. The primary analysis used a likelihood‐based approach to assess efficacy: mean change to the planned endpoint of the trial assuming patients stayed on drug. Secondarily, effectiveness was assessed using a multiple imputation approach. The imputation model—derived solely from the placebo group—was used to impute missing values for both the drug and placebo groups. Therefore, this so‐called placebo multiple imputation (a.k.a. controlled imputation) approach assumed patients had reduced benefit from the drug after discontinuing it. Results from the example data provided clear evidence of efficacy for the experimental drug and characterized its effectiveness. Data after discontinuation of study medication were not required for these analyses. Given the idiosyncratic nature of drug development, no estimand or approach is universally appropriate. However, the general practice of pairing efficacy and effectiveness estimands may often be useful in understanding the overall risks and benefits of a drug. Controlled imputation approaches, such as placebo multiple imputation, can be a flexible and transparent framework for formulating primary analyses of effectiveness estimands and sensitivity analyses for efficacy estimands. Copyright © 2012 John Wiley & Sons, Ltd.     

Imputation of Household Survey Data Using Linear Mixed Models

Mixed models are regularly used in the analysis of clustered data, but are only recently being used for imputation of missing data. In household surveys where multiple people are selected from each household, imputation of missing values should preserve the structure pertaining to people within households and should not artificially change the apparent intracluster correlation (ICC). This paper focuses on the use of multilevel models for imputation of missing data in household surveys. In particular, the performance of a best linear unbiased predictor for both stochastic and deterministic imputation using a linear mixed model is compared to imputation based on a single level linear model, both with and without information about household respondents. In this paper an evaluation is carried out in the context of imputing hourly wage rate in the Household, Income and Labour Dynamics of Australia Survey. Nonresponse is generated under various assumptions about the missingness mechanism for persons and households, and with low, moderate and high intra‐household correlation to assess the benefits of the multilevel imputation model under different conditions. The mixed model and single level model with information about the household respondent lead to clear improvements when the ICC is moderate or high, and when there is informative missingness.     

Empirical Likelihood for Partially Non Linear Models with Missing Response Variables at Random

This article is concerned with partially non linear models when the response variables are missing at random. We examine the empirical likelihood (EL) ratio statistics for unknown parameter in non linear function based on complete-case data, semiparametric regression imputation, and bias-corrected imputation. All the proposed statistics are proven to be asymptotically chi-square distribution under some suitable conditions. Simulation experiments are conducted to compare the finite sample behaviors of the proposed approaches in terms of confidence intervals. It showed that the EL method has advantage compared to the conventional method, and moreover, the imputation technique performs better than the complete-case data.     

Multiple imputation of a randomly censored covariate improves logistic regression analysis

Randomly censored covariates arise frequently in epidemiologic studies. The most commonly used methods, including complete case and single imputation or substitution, suffer from inefficiency and bias. They make strong parametric assumptions or they consider limit of detection censoring only. We employ multiple imputation, in conjunction with semi-parametric modeling of the censored covariate, to overcome these shortcomings and to facilitate robust estimation. We develop a multiple imputation approach for randomly censored covariates within the framework of a logistic regression model. We use the non-parametric estimate of the covariate distribution or the semi-parametric Cox model estimate in the presence of additional covariates in the model. We evaluate this procedure in simulations, and compare its operating characteristics to those from the complete case analysis and a survival regression approach. We apply the procedures to an Alzheimer's study of the association between amyloid positivity and maternal age of onset of dementia. Multiple imputation achieves lower standard errors and higher power than the complete case approach under heavy and moderate censoring and is comparable under light censoring. The survival regression approach achieves the highest power among all procedures, but does not produce interpretable estimates of association. Multiple imputation offers a favorable alternative to complete case analysis and ad hoc substitution methods in the presence of randomly censored covariates within the framework of logistic regression.     

Missing data techniques for multilevel data: implications of model misspecification

When modeling multilevel data, it is important to accurately represent the interdependence of observations within clusters. Ignoring data clustering may result in parameter misestimation. However, it is not well established to what degree parameter estimates are affected by model misspecification when applying missing data techniques (MDTs) to incomplete multilevel data. We compare the performance of three MDTs with incomplete hierarchical data. We consider the impact of imputation model misspecification on the quality of parameter estimates by employing multiple imputation under assumptions of a normal model (MI/NM) with two-level cross-sectional data when values are missing at random on the dependent variable at rates of 10%, 30%, and 50%. Five criteria are used to compare estimates from MI/NM to estimates from MI assuming a linear mixed model (MI/LMM) and maximum likelihood estimation to the same incomplete data sets. With 10% missing data (MD), techniques performed similarly for fixed-effects estimates, but variance components were biased with MI/NM. Effects of model misspecification worsened at higher rates of MD, with the hierarchical structure of the data markedly underrepresented by biased variance component estimates. MI/LMM and maximum likelihood provided generally accurate and unbiased parameter estimates but performance was negatively affected by increased rates of MD.     

Mixture of latent trait analyzers for model-based clustering of categorical data

Model-based clustering methods for continuous data are well established and commonly used in a wide range of applications. However, model-based clustering methods for categorical data are less standard. Latent class analysis is a commonly used method for model-based clustering of binary data and/or categorical data, but due to an assumed local independence structure there may not be a correspondence between the estimated latent classes and groups in the population of interest. The mixture of latent trait analyzers model extends latent class analysis by assuming a model for the categorical response variables that depends on both a categorical latent class and a continuous latent trait variable; the discrete latent class accommodates group structure and the continuous latent trait accommodates dependence within these groups. Fitting the mixture of latent trait analyzers model is potentially difficult because the likelihood function involves an integral that cannot be evaluated analytically. We develop a variational approach for fitting the mixture of latent trait models and this provides an efficient model fitting strategy. The mixture of latent trait analyzers model is demonstrated on the analysis of data from the National Long Term Care Survey (NLTCS) and voting in the U.S. Congress. The model is shown to yield intuitive clustering results and it gives a much better fit than either latent class analysis or latent trait analysis alone.     

Probabilistic Principal Component Analysis

Principal component analysis (PCA) is a ubiquitous technique for data analysis and processing, but one which is not based on a probability model. We demonstrate how the principal axes of a set of observed data vectors may be determined through maximum likelihood estimation of parameters in a latent variable model that is closely related to factor analysis. We consider the properties of the associated likelihood function, giving an EM algorithm for estimating the principal subspace iteratively, and discuss, with illustrative examples, the advantages conveyed by this probabilistic approach to PCA.     

Skew-normal factor analysis models with incomplete data

Traditional factor analysis (FA) rests on the assumption of multivariate normality. However, in some practical situations, the data do not meet this assumption; thus, the statistical inference made from such data may be misleading. This paper aims at providing some new tools for the skew-normal (SN) FA model when missing values occur in the data. In such a model, the latent factors are assumed to follow a restricted version of multivariate SN distribution with additional shape parameters for accommodating skewness. We develop an analytically feasible expectation conditional maximization algorithm for carrying out parameter estimation and imputation of missing values under missing at random mechanisms. The practical utility of the proposed methodology is illustrated with two real data examples and the results are compared with those obtained from the traditional FA counterparts.     

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.     

Latent Variable Models for Mixed Discrete and Continuous Outcomes

We propose a latent variable model for mixed discrete and continuous outcomes. The model accommodates any mixture of outcomes from an exponential family and allows for arbitrary covariate effects, as well as direct modelling of covariates on the latent variable. An EM algorithm is proposed for parameter estimation and estimates of the latent variables are produced as a by-product of the analysis. A generalized likelihood ratio test can be used to test the significance of covariates affecting the latent outcomes. This method is applied to birth defects data, where the outcomes of interest are continuous measures of size and binary indicators of minor physical anomalies. Infants who were exposed in utero to anticonvulsant medications are compared with controls.