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 mixed effects model for analyzing area under the curve of longitudinally measured biomarkers with missing data

A simple approach for analyzing longitudinally measured biomarkers is to calculate summary measures such as the area under the curve (AUC) for each individual and then compare the mean AUC between treatment groups using methods such as t test. This two-step approach is difficult to implement when there are missing data since the AUC cannot be directly calculated for individuals with missing measurements. Simple methods for dealing with missing data include the complete case analysis and imputation. A recent study showed that the estimated mean AUC difference between treatment groups based on the linear mixed model (LMM), rather than on individually calculated AUCs by simple imputation, has negligible bias under random missing assumptions and only small bias when missing is not at random. However, this model assumes the outcome to be normally distributed, which is often violated in biomarker data. In this paper, we propose to use a LMM on log-transformed biomarkers, based on which statistical inference for the ratio, rather than difference, of AUC between treatment groups is provided. The proposed method can not only handle the potential baseline imbalance in a randomized trail but also circumvent the estimation of the nuisance variance parameters in the log-normal model. The proposed model is applied to a recently completed large randomized trial studying the effect of nicotine reduction on biomarker exposure of smokers.     

IMPROVING POPULATION-SPECIFIC ALLELE FREQUENCY ESTIMATES BY ADAPTING SUPPLEMENTAL DATA: AN EMPIRICAL BAYES APPROACH

Estimation of the allele frequency at genetic markers is a key ingredient in biological and biomedical research, such as studies of human genetic variation or of the genetic etiology of heritable traits. As genetic data becomes increasingly available, investigators face a dilemma: when should data from other studies and population subgroups be pooled with the primary data? Pooling additional samples will generally reduce the variance of the frequency estimates; however, used inappropriately, pooled estimates can be severely biased due to population stratification. Because of this potential bias, most investigators avoid pooling, even for samples with the same ethnic background and residing on the same continent. Here, we propose an empirical Bayes approach for estimating allele frequencies of single nucleotide polymorphisms. This procedure adaptively incorporates genotypes from related samples, so that more similar samples have a greater influence on the estimates. In every example we have considered, our estimator achieves a mean squared error (MSE) that is smaller than either pooling or not, and sometimes substantially improves over both extremes. The bias introduced is small, as is shown by a simulation study that is carefully matched to a real data example. Our method is particularly useful when small groups of individuals are genotyped at a large number of markers, a situation we are likely to encounter in a genome-wide association study.     

Parametric fractional imputation for nonignorable missing data

Parameter estimation with missing data is a frequently encountered problem in statistics. Imputation is often used to facilitate the parameter estimation by simply applying the complete-sample estimators to the imputed dataset.In this article, we consider the problem of parameter estimation with nonignorable missing data using the approach of parametric fractional imputation proposed by Kim (2011). Using the fractional weights, the E-step of the EM algorithm can be approximated by the weighted mean of the imputed data likelihood where the fractional weights are computed from the current value of the parameter estimates. Calibration fractional imputation is also considered as a way for improving the Monte Carlo approximation in the fractional imputation. Variance estimation is also discussed. Results from two simulation studies are presented to compare the proposed method with the existing methods. A real data example from the Korea Labor and Income Panel Survey (KLIPS) is also presented.     

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.     

Applying the rescaling bootstrap under imputation: a simulation study

Resampling methods are a common measure to estimate the variance of a statistic of interest when data consist of nonresponse and imputation is used as compensation. Applying resampling methods usually means that subsamples are drawn from the original sample and that variance estimates are computed based on point estimators of several subsamples. However, newer resampling methods such as the rescaling bootstrap of Chipperfield and Preston [Efficient bootstrap for business surveys. Surv Methodol. 2007;33:167–172] include all elements of the original sample in the computation of its point estimator. Thus, procedures to consider imputation in resampling methods cannot be applied in the ordinary way. For such methods, modifications are necessary. This paper presents an approach applying newer resampling methods for imputed data. The Monte Carlo simulation study conducted in the paper shows that the proposed approach leads to reliable variance estimates in contrast to other modifications.     

Nonparametric methods for the estimation of imputation uncertainty

It is cleared in recent researches that the raising of missing values in datasets is inevitable. Imputation of missing data is one of the several methods which have been introduced to overcome this issue. Imputation techniques are trying to answer the case of missing data by covering missing values with reasonable estimates permanently. There are a lot of benefits for these procedures rather than their drawbacks. The operation of these methods has not been clarified, which means that they provide mistrust among analytical results. One approach to evaluate the outcomes of the imputation process is estimating uncertainty in the imputed data. Nonparametric methods are appropriate to estimating the uncertainty when data are not followed by any particular distribution. This paper deals with a nonparametric method for estimation and testing the significance of the imputation uncertainty, which is based on Wilcoxon test statistic, and which could be employed for estimating the precision of the imputed values created by imputation methods. This proposed procedure could be employed to judge the possibility of the imputation process for datasets, and to evaluate the influence of proper imputation methods when they are utilized to the same dataset. This proposed approach has been compared with other nonparametric resampling methods, including bootstrap and jackknife to estimate uncertainty in the imputed data under the Bayesian bootstrap imputation method. The ideas supporting the proposed method are clarified in detail, and a simulation study, which indicates how the approach has been employed in practical situations, is illustrated.     

Model selection and model averaging for semiparametric partially linear models with missing data

We study model selection and model averaging in semiparametric partially linear models with missing responses. An imputation method is used to estimate the linear regression coefficients and the nonparametric function. We show that the corresponding estimators of the linear regression coefficients are asymptotically normal. Then a focused information criterion and frequentist model average estimators are proposed and their theoretical properties are established. Simulation studies are performed to demonstrate the superiority of the proposed methods over the existing strategies in terms of mean squared error and coverage probability. Finally, the approach is applied to a real data case.     

Variable selection for high-dimensional generalized linear model with block-missing data

In modern scientific research, multiblock missing data emerges with synthesizing information across multiple studies. However, existing imputation methods for handling block-wise missing data either focus on the single-block missing pattern or heavily rely on the model structure. In this study, we propose a single regression-based imputation algorithm for multiblock missing data. First, we conduct a sparse precision matrix estimation based on the structure of block-wise missing data. Second, we impute the missing blocks with their means conditional on the observed blocks. Theoretical results about variable selection and estimation consistency are established in the context of a generalized linear model. Moreover, simulation studies show that compared with existing methods, the proposed imputation procedure is robust to various missing mechanisms because of the good properties of regression imputation. An application to Alzheimer's Disease Neuroimaging Initiative data also confirms the superiority of our proposed method.     

Methods for missing covariates in logistic regression

Various methods have been suggested in the literature to handle a missing covariate in the presence of surrogate covariates. These methods belong to one of two paradigms. In the imputation paradigm, Pepe and Fleming (1991) and Reilly and Pepe (1995) suggested filling in missing covariates using the empirical distribution of the covariate obtained from the observed data. We can proceed one step further by imputing the missing covariate using nonparametric maximum likelihood estimates (NPMLE) of the density of the covariate. Recently Murphy and Van der Vaart (1998a) showed that such an approach yields a consistent, asymptotically normal, and semiparametric efficient estimate for the logistic regression coefficient. In the weighting paradigm, Zhao and Lipsitz (1992) suggested an estimating function using completely observed records after weighting inversely by the probability of observation. An extension of this weighting approach designed to achieve semiparametric efficient bound is considered by Robins, Hsieh and Newey (RHN) (1995). The two ends of each paradigm (NPMLE and RHN) attain the efficiency bound and are asymptotically equivalent. However, both require a substantial amount of computation. A question arises whether and when, in practical situations, this extensive computation is worthwhile. In this paper we investigate the performance of single and multiple imputation estimates, weighting estimates, semiparametric efficient estimates, and two new imputation estimates. Simulation studies suggest that the sample size should be substantially large (e.g. n=2000) for NPMLE and RHN to be more efficient than simpler imputation estimates. When the sample size is moderately large (n≤ 1500), simpler imputation estimates have as small a variance as semiparametric efficient estimates.     

Bayesian inference for stochastic multitype epidemics in structured populations via random graphs

Summary.  The paper is concerned with new methodology for statistical inference for final outcome infectious disease data using certain structured population stochastic epidemic models. A major obstacle to inference for such models is that the likelihood is both analytically and numerically intractable. The approach that is taken here is to impute missing information in the form of a random graph that describes the potential infectious contacts between individuals. This level of imputation overcomes various constraints of existing methodologies and yields more detailed information about the spread of disease. The methods are illustrated with both real and test data.     

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.     

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.     

Navigating choices when applying multiple imputation in the presence of multi-level categorical interaction effects

Multiple imputation (MI) is an appealing option for handling missing data. When implementing MI, however, users need to make important decisions to obtain estimates with good statistical properties. One such decision involves the choice of imputation model–the joint modeling (JM) versus fully conditional specification (FCS) approach. Another involves the choice of method to handle interactions. These include imputing the interaction term as any other variable (active imputation), or imputing the main effects and then deriving the interaction (passive imputation). Our study investigates the best approach to perform MI in the presence of interaction effects involving two categorical variables. Such effects warrant special attention as they involve multiple correlated parameters that are handled differently under JM and FCS modeling. Through an extensive simulation study, we compared active, passive and an improved passive approach under FCS, as JM precludes passive imputation. We additionally compared JM and FCS techniques using active imputation. Performance between active and passive imputation was comparable. The improved passive approach proved superior to the other two particularly when the number of parameters corresponding to the interaction was large. JM without rounding and FCS using active imputation were also mostly comparable, with JM outperforming FCS when the number of parameters was large. In a direct comparison of JM active and FCS improved passive, the latter was the clear winner. We recommend improved passive imputation under FCS along with sensitivity analyses to handle multi-level interaction terms.     

Missing data sensitivity analysis for recurrent event data using controlled imputation

Statistical analyses of recurrent event data have typically been based on the missing at random assumption. One implication of this is that, if data are collected only when patients are on their randomized treatment, the resulting de jure estimator of treatment effect corresponds to the situation in which the patients adhere to this regime throughout the study. For confirmatory analysis of clinical trials, sensitivity analyses are required to investigate alternative de facto estimands that depart from this assumption. Recent publications have described the use of multiple imputation methods based on pattern mixture models for continuous outcomes, where imputation for the missing data for one treatment arm (e.g. the active arm) is based on the statistical behaviour of outcomes in another arm (e.g. the placebo arm). This has been referred to as controlled imputation or reference‐based imputation. In this paper, we use the negative multinomial distribution to apply this approach to analyses of recurrent events and other similar outcomes. The methods are illustrated by a trial in severe asthma where the primary endpoint was rate of exacerbations and the primary analysis was based on the negative binomial model. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

稳健高效的高维成分数据近似零值插补方法及应用

随着计算机技术的迅猛发展,高维成分数据不断涌现并伴有大量近似零值和缺失,数据的高维特性不仅给传统统计方法带来了巨大的挑战,其厚尾特征、复杂的协方差结构也使得理论分析难上加难。于是如何对高维成分数据的近似零值进行稳健的插补,挖掘潜在的内蕴结构成为当今学者研究的焦点。对此,本文结合修正的EM算法,提出基于R型聚类的Lasso-分位回归插补法(SubLQR)对高维成分数据的近似零值问题予以解决。与现有高维近似零值插补方法相比,本文所提出的SubLQR具有如下优势。①稳健全面性:利用Lasso-分位回归方法,不仅可以有效地探测到响应变量的整个条件分布,还能提供更加真实的高维稀疏模式;②有效准确性:采用基于R型聚类的思想进行插补,可以降低计算复杂度,极大提高插补的精度。模拟研究证实,本文提出的SubLQR高效灵活准确,特别在零值、异常值较多的情形更具优势。最后将SubLQR方法应用于罕见病代谢组学研究中,进一步表明本文所提出的方法具有广泛的适用性。     

Estimation in Regressive Logistic Regression Analyses of Familial Data with Missing Outcomes

This paper examines a number of methods of handling missing outcomes in regressive logistic regression modelling of familial binary data, and compares them with an EM algorithm approach via a simulation study. The results indicate that a strategy based on imputation of missing values leads to biased estimates, and that a strategy of excluding incomplete families has a substantial effect on the variability of the parameter estimates. Recommendations are made which depend, amongst other factors, on the amount of missing data and on the availability of software.     

Propensity score matching and stratification using multiparty data without pooling

Matching and stratification based on confounding factors or propensity scores (PS) are powerful approaches for reducing confounding bias in indirect treatment comparisons. However, implementing these approaches requires pooled individual patient data (IPD). The research presented here was motivated by an indirect comparison between a single-armed trial in acute myeloid leukemia (AML), and two external AML registries with current treatments for a control. For confidentiality reasons, IPD cannot be pooled. Common approaches to adjusting confounding bias, such as PS matching or stratification, cannot be applied as 1) a model for PS, for example, a logistic model, cannot be fitted without pooling covariate data; 2) pooling response data may be necessary for some statistical inference (e.g., estimating the SE of mean difference of matched pairs) after PS matching. We propose a set of approaches that do not require pooling IPD, using a combination of methods including a linear discriminant for matching and stratification, and secure multiparty computation for estimation of within-pair sample variance and for calculations involving multiple control sources. The approaches only need to share aggregated data offline, rather than real-time secure data transfer, as required by typical secure multiparty computation for model fitting. For survival analysis, we propose an approach using restricted mean survival time. A simulation study was conducted to evaluate this approach in several scenarios, in particular, with a mixture of continuous and binary covariates. The results confirmed the robustness and efficiency of the proposed approach. A real data example is also provided for illustration.     

Missing item imputation for quality-of-life instruments with application to asthma quality-of-life questionnaires

There has been increasing use of quality-of-life (QoL) instruments in drug development. Missing item values often occur in QoL data. A common approach to solve this problem is to impute the missing values before scoring. Several imputation procedures, such as imputing with the most correlated item and imputing with a row/column model or an item response model, have been proposed. We examine these procedures using data from two clinical trials, in which the original asthma quality-of-life questionnaire (AQLQ) and the miniAQLQ were used. We propose two modifications to existing procedures: truncating the imputed values to eliminate outliers and using the proportional odds model as the item response model for imputation. We also propose a novel imputation method based on a semi-parametric beta regression so that the imputed value is always in the correct range and illustrate how this approach can easily be implemented in commonly used statistical software. To compare these approaches, we deleted 5% of item values in the data according to three different missingness mechanisms, imputed them using these approaches and compared the imputed values with the true values. Our comparison showed that the row/column-model-based imputation with truncation generally performed better, whereas our new approach had better performance under a number scenarios.