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.     

Inferences on missing information under multiple imputation and two-stage multiple imputation

In the presence of missing values, researchers may be interested in the rates of missing information. The rates of missing information are (a) important for assessing how the missing information contributes to inferential uncertainty about, Q, the population quantity of interest, (b) are an important component in the decision of the number of imputations, and (c) can be used to test model uncertainty and model fitting. In this article I will derive the asymptotic distribution of the rates of missing information in two scenarios: the conventional multiple imputation (MI), and the two-stage MI. Numerically I will show that the proposed asymptotic distribution agrees with the simulated one. I will also suggest the number of imputations needed to obtain reliable missing information rate estimates for each method, based on the asymptotic distribution.     

Comparisons of imputation methods with application to assess factors associated with self efficacy of physical activity in breast cancer survivors

ABSTRACT

Missing data are commonly encountered in self-reported measurements and questionnaires. It is crucial to treat missing values using appropriate method to avoid bias and reduction of power. Various types of imputation methods exist, but it is not always clear which method is preferred for imputation of data with non-normal variables. In this paper, we compared four imputation methods: mean imputation, quantile imputation, multiple imputation, and quantile regression multiple imputation (QRMI), using both simulated and real data investigating factors affecting self-efficacy in breast cancer survivors. The results displayed an advantage of using multiple imputation, especially QRMI when data are not normal.     

Balanced k-nearest neighbour imputation

Random imputation is an interesting class of imputation methods to handle item nonresponse because it tends to preserve the distribution of the imputed variable. However, such methods amplify the total variance of the estimators because values are imputed at random. This increase in variance is called imputation variance. In this paper, we propose a new random hot-deck imputation method that is based on the k-nearest neighbour methodology. It replaces the missing value of a unit with the observed value of a similar unit. Calibration and balanced sampling are applied to minimize the imputation variance. Moreover, our proposed method provides triple protection against nonresponse bias. This means that if at least one out of three specified models holds, then the resulting total estimator is unbiased. Finally, our approach allows the user to perform consistency edits and to impute simultaneously.     

Robust Model-Based Inference for Incomplete Data via Penalized Spline Propensity Prediction

Parametric model-based regression imputation is commonly applied to missing-data problems, but is sensitive to misspecification of the imputation model. Little and An (2004 Little , R. J. A. , An , H. ( 2004 ). Robust likelihood-based analysis of multivariate data with missing values . Statistica Sinica 14 : 949 – 968 .[Web of Science ®] , [Google Scholar]) proposed a semiparametric approach called penalized spline propensity prediction (PSPP), where the variable with missing values is modeled by a penalized spline (P-Spline) of the response propensity score, which is logit of the estimated probability of being missing given the observed variables. Variables other than the response propensity are included parametrically in the imputation model. However they only considered point estimation based on single imputation with PSPP. We consider here three approaches to standard errors estimation incorporating the uncertainty due to non response: (a) standard errors based on the asymptotic variance of the PSPP estimator, ignoring sampling error in estimating the response propensity; (b) standard errors based on the bootstrap method; and (c) multiple imputation-based standard errors using draws from the joint posterior predictive distribution of missing values under the PSPP model. Simulation studies suggest that the bootstrap and multiple imputation approaches yield good inferences under a range of simulation conditions, with multiple imputation showing some evidence of closer to nominal confidence interval coverage when the sample size is small.     

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.     

Reference‐based sensitivity analysis for time‐to‐event data

The analysis of time‐to‐event data typically makes the censoring at random assumption, ie, that—conditional on covariates in the model—the distribution of event times is the same, whether they are observed or unobserved (ie, right censored). When patients who remain in follow‐up stay on their assigned treatment, then analysis under this assumption broadly addresses the de jure, or “while on treatment strategy” estimand. In such cases, we may well wish to explore the robustness of our inference to more pragmatic, de facto or “treatment policy strategy,” assumptions about the behaviour of patients post‐censoring. This is particularly the case when censoring occurs because patients change, or revert, to the usual (ie, reference) standard of care. Recent work has shown how such questions can be addressed for trials with continuous outcome data and longitudinal follow‐up, using reference‐based multiple imputation. For example, patients in the active arm may have their missing data imputed assuming they reverted to the control (ie, reference) intervention on withdrawal. Reference‐based imputation has two advantages: (a) it avoids the user specifying numerous parameters describing the distribution of patients' postwithdrawal data and (b) it is, to a good approximation, information anchored, so that the proportion of information lost due to missing data under the primary analysis is held constant across the sensitivity analyses. In this article, we build on recent work in the survival context, proposing a class of reference‐based assumptions appropriate for time‐to‐event data. We report a simulation study exploring the extent to which the multiple imputation estimator (using Rubin's variance formula) is information anchored in this setting and then illustrate the approach by reanalysing data from a randomized trial, which compared medical therapy with angioplasty for patients presenting with angina.     

A distance-based rounding strategy for post-imputation ordinal data

Multiple imputation has emerged as a widely used model-based approach in dealing with incomplete data in many application areas. Gaussian and log-linear imputation models are fairly straightforward to implement for continuous and discrete data, respectively. However, in missing data settings which include a mix of continuous and discrete variables, correct specification of the imputation model could be a daunting task owing to the lack of flexible models for the joint distribution of variables of different nature. This complication, along with accessibility to software packages that are capable of carrying out multiple imputation under the assumption of joint multivariate normality, appears to encourage applied researchers for pragmatically treating the discrete variables as continuous for imputation purposes, and subsequently rounding the imputed values to the nearest observed category. In this article, I introduce a distance-based rounding approach for ordinal variables in the presence of continuous ones. The first step of the proposed rounding process is predicated upon creating indicator variables that correspond to the ordinal levels, followed by jointly imputing all variables under the assumption of multivariate normality. The imputed values are then converted to the ordinal scale based on their Euclidean distances to a set of indicators, with minimal distance corresponding to the closest match. I compare the performance of this technique to crude rounding via commonly accepted accuracy and precision measures with simulated data sets.     

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.     

Examining the robustness of fully synthetic data techniques for data with binary variables

There is a growing demand for public use data while at the same time there are increasing concerns about the privacy of personal information. One proposed method for accomplishing both goals is to release data sets that do not contain real values but yield the same inferences as the actual data. The idea is to view confidential data as missing and use multiple imputation techniques to create synthetic data sets. In this article, we compare techniques for creating synthetic data sets in simple scenarios with a binary variable.     

Validity and efficiency in analyzing ordinal responses with missing observations

This article addresses issues in creating public-use data files in the presence of missing ordinal responses and subsequent statistical analyses of the dataset by users. The authors propose a fully efficient fractional imputation (FI) procedure for ordinal responses with missing observations. The proposed imputation strategy retrieves the missing values through the full conditional distribution of the response given the covariates and results in a single imputed data file that can be analyzed by different data users with different scientific objectives. Two most critical aspects of statistical analyses based on the imputed data set,  validity  and  efficiency, are examined through regression analysis involving the ordinal response and a selected set of covariates. It is shown through both theoretical development and simulation studies that, when the ordinal responses are missing at random, the proposed FI procedure leads to valid and highly efficient inferences as compared to existing methods. Variance estimation using the fractionally imputed data set is also discussed. The Canadian Journal of Statistics 48: 138–151; 2020 © 2019 Statistical Society of Canada     

A structured framework for assessing sensitivity to missing data assumptions in longitudinal clinical trials

The objective of this research was to demonstrate a framework for drawing inference from sensitivity analyses of incomplete longitudinal clinical trial data via a re‐analysis of data from a confirmatory clinical trial in depression. A likelihood‐based approach that assumed missing at random (MAR) was the primary analysis. Robustness to departure from MAR was assessed by comparing the primary result to those from a series of analyses that employed varying missing not at random (MNAR) assumptions (selection models, pattern mixture models and shared parameter models) and to MAR methods that used inclusive models. The key sensitivity analysis used multiple imputation assuming that after dropout the trajectory of drug‐treated patients was that of placebo treated patients with a similar outcome history (placebo multiple imputation). This result was used as the worst reasonable case to define the lower limit of plausible values for the treatment contrast. The endpoint contrast from the primary analysis was ? 2.79 (p = .013). In placebo multiple imputation, the result was ? 2.17. Results from the other sensitivity analyses ranged from ? 2.21 to ? 3.87 and were symmetrically distributed around the primary result. Hence, no clear evidence of bias from missing not at random data was found. In the worst reasonable case scenario, the treatment effect was 80% of the magnitude of the primary result. Therefore, it was concluded that a treatment effect existed. The structured sensitivity framework of using a worst reasonable case result based on a controlled imputation approach with transparent and debatable assumptions supplemented a series of plausible alternative models under varying assumptions was useful in this specific situation and holds promise as a generally useful framework. Copyright © 2012 John Wiley & Sons, Ltd.     

Multiple imputation using multivariate gh transformations

Multiple imputation has emerged as a popular approach to handling data sets with missing values. For incomplete continuous variables, imputations are usually produced using multivariate normal models. However, this approach might be problematic for variables with a strong non-normal shape, as it would generate imputations incoherent with actual distributions and thus lead to incorrect inferences. For non-normal data, we consider a multivariate extension of Tukey's gh distribution/transformation [38] to accommodate skewness and/or kurtosis and capture the correlation among the variables. We propose an algorithm to fit the incomplete data with the model and generate imputations. We apply the method to a national data set for hospital performance on several standard quality measures, which are highly skewed to the left and substantially correlated with each other. We use Monte Carlo studies to assess the performance of the proposed approach. We discuss possible generalizations and give some advices to practitioners on how to handle non-normal incomplete data.     

An Examination of Discrepancies in Multiple Imputation Procedures Between SAS® and SPSS®

Multiple imputation (MI) has become a feasible method to replace missing data due to the rapid development of computer technology over the past three decades. Nonetheless, a unique issue with MI hinges on the fact that different software packages can give different results. Even when one begins with the same random number seed, conflicting findings can be obtained from the same data under an identical imputation model between SAS® and SPSS®. Consequently, as illustrated in this article, a predictor variable can be claimed both significant and not significant depending on the software being used. Based on the considerations of multiple imputation steps, including result pooling, default selection, and different numbers of imputations, practical suggestions are provided to minimize the discrepancies in the results obtained when using MI. Features of Stata® are briefly reviewed in the Discussion section to broaden the comparison of MI computing across widely used software packages.     

Performance of standard imputation methods for missing quality of life data as covariate in survival analysis based on simulations from the International Breast Cancer Study Group Trials VI and VII*

Abstract

Imputation methods for missing data on a time-dependent variable within time-dependent Cox models are investigated in a simulation study. Quality of life (QoL) assessments were removed from the complete simulated datasets, which have a positive relationship between QoL and disease-free survival (DFS) and delayed chemotherapy and DFS, by missing at random and missing not at random (MNAR) mechanisms. Standard imputation methods were applied before analysis. Method performance was influenced by missing data mechanism, with one exception for simple imputation. The greatest bias occurred under MNAR and large effect sizes. It is important to carefully investigate the missing data mechanism.     

Stochastic EM algorithm of a finite mixture model from hurdle Poisson distribution with missing responses

ABSTRACT

In this article, a finite mixture model of hurdle Poisson distribution with missing outcomes is proposed, and a stochastic EM algorithm is developed for obtaining the maximum likelihood estimates of model parameters and mixing proportions. Specifically, missing data is assumed to be missing not at random (MNAR)/non ignorable missing (NINR) and the corresponding missingness mechanism is modeled through probit regression. To improve the algorithm efficiency, a stochastic step is incorporated into the E-step based on data augmentation, whereas the M-step is solved by the method of conditional maximization. A variation on Bayesian information criterion (BIC) is also proposed to compare models with different number of components with missing values. The considered model is a general model framework and it captures the important characteristics of count data analysis such as zero inflation/deflation, heterogeneity as well as missingness, providing us with more insight into the data feature and allowing for dispersion to be investigated more fully and correctly. Since the stochastic step only involves simulating samples from some standard distributions, the computational burden is alleviated. Once missing responses and latent variables are imputed to replace the conditional expectation, our approach works as part of a multiple imputation procedure. A simulation study and a real example illustrate the usefulness and effectiveness of our methodology.     

A fresh imputing survey methodology using sensible constraints on study and auxiliary variables: dubious random non-response

In this paper, we introduce a fresh methodology for imputing missing values by making use of sensible constraints on both a study variable and auxiliary variables that are correlated with the variable of interest. The resultant estimator based on these imputed values is shown to lead to the regression type method of imputation in survey sampling. Furthermore, when the data are hybrid of both that missing at random and missing complexly at random, the resultant estimator is shown to be a consistent estimator that has asymptotic mean squared error equal to that of the linear regression method of imputation. A generalization to any type of method of imputation is possible and has been included at the end.     

Comparison of alternative imputation methods for ordinal data

In this article, we compare alternative missing imputation methods in the presence of ordinal data, in the framework of CUB (Combination of Uniform and (shifted) Binomial random variable) models. Various imputation methods are considered, as are univariate and multivariate approaches. The first step consists of running a simulation study designed by varying the parameters of the CUB model, to consider and compare CUB models as well as other methods of missing imputation. We use real datasets on which to base the comparison between our approach and some general methods of missing imputation for various missing data mechanisms.     

GRAPHICAL SENSITIVITY ANALYSIS WITH DIFFERENT METHODS OF IMPUTATION FOR A TRIAL WITH PROBABLE NON‐IGNORABLE MISSING DATA

Graphical sensitivity analyses have recently been recommended for clinical trials with non‐ignorable missing outcome. We demonstrate an adaptation of this methodology for a continuous outcome of a trial of three cognitive‐behavioural therapies for mild depression in primary care, in which one arm had unexpectedly high levels of missing data. Fixed‐value and multiple imputations from a normal distribution (assuming either varying mean and fixed standard deviation, or fixed mean and varying standard deviation) were used to obtain contour plots of the contrast estimates with their P‐values superimposed, their confidence intervals, and the root mean square errors. Imputation was based either on the outcome value alone, or on change from baseline. The plots showed fixed‐value imputation to be more sensitive than imputing from a normal distribution, but the normally distributed imputations were subject to sampling noise. The contours of the sensitivity plots were close to linear in appearance, with the slope approximately equal to the ratio of the proportions of subjects with missing data in each trial arm.     

Multiple imputation for ordinal longitudinal data with monotone missing data patterns

Missing data often complicate the analysis of scientific data. Multiple imputation is a general purpose technique for analysis of datasets with missing values. The approach is applicable to a variety of missing data patterns but often complicated by some restrictions like the type of variables to be imputed and the mechanism underlying the missing data. In this paper, the authors compare the performance of two multiple imputation methods, namely fully conditional specification and multivariate normal imputation in the presence of ordinal outcomes with monotone missing data patterns. Through a simulation study and an empirical example, the authors show that the two methods are indeed comparable meaning any of the two may be used when faced with scenarios, at least, as the ones presented here.