Multiple imputation in high-dimensional data with variable selection

BackgroundMultiple imputation is frequently used to deal with missing data in healthcare research. Although it is known that the outcome should be included in the imputation model when imputing missing covariate values, it is not known whether it should be imputed. Similarly no clear recommendations exist on: the utility of incorporating a secondary outcome, if available, in the imputation model; the level of protection offered when data are missing not-at-random; the implications of the dataset size and missingness levels.MethodsWe used realistic assumptions to generate thousands of datasets across a broad spectrum of contexts: three mechanisms of missingness (completely at random; at random; not at random); varying extents of missingness (20–80% missing data); and different sample sizes (1,000 or 10,000 cases). For each context we quantified the performance of a complete case analysis and seven multiple imputation methods which deleted cases with missing outcome before imputation, after imputation or not at all; included or did not include the outcome in the imputation models; and included or did not include a secondary outcome in the imputation models. Methods were compared on mean absolute error, bias, coverage and power over 1,000 datasets for each scenario.ResultsOverall, there was very little to separate multiple imputation methods which included the outcome in the imputation model. Even when missingness was quite extensive, all multiple imputation approaches performed well. Incorporating a secondary outcome, moderately correlated with the outcome of interest, made very little difference. The dataset size and the extent of missingness affected performance, as expected. Multiple imputation methods protected less well against missingness not at random, but did offer some protection.ConclusionsAs long as the outcome is included in the imputation model, there are very small performance differences between the possible multiple imputation approaches: no outcome imputation, imputation or imputation and deletion. All informative covariates, even with very high levels of missingness, should be included in the multiple imputation model. Multiple imputation offers some protection against a simple missing not at random mechanism.

Missing data are nearly always a problem in research, and missing values represent a serious threat to the validity of inferences drawn from findings. Increasingly, social science researchers are turning to multiple imputation to handle missing data. Multiple imputation, in which missing values are replaced by values repeatedly drawn from conditional probability distributions, is an appropriate method for handling missing data when values are not missing completely at random. However, use of this method requires developing an imputation model from the observed data. This is typically a rigorous and time-consuming process. To encourage wider adoption of multiple imputation in social work research, a simple framework for designing imputation models is presented. The framework and its ability to generate unbiased estimates are demonstrated in a simulation study. KEY WORDS: missing data; multiple imputation; nonresponse ********** Missing data are ubiquitous in social research, and missingness or nonresponse can represent a threat to the validity of inferences because of undue effects on efficiency, power, and parameter bias (Shadish, Cook, & Campbell, 2002). Social work researchers are now addressing missing data in a more rigorous manner. Recently, Saunders et al. (2006) and Choi, Golder, Gillmore, and Morrison (2005) described important data imputation methods and dispelled misunderstandings regarding popular imputation methods, such as mean substitution. Recent advances in analytic methods, such as multiple imputation (MI), are taking hold in social work research. With MI, missing values are replaced with values repeatedly drawn from simulated conditional probability distributions (Schafer, 1997), thus creating multiple versions of the data set. Each version of the data set is analyzed according to the data analysis model, and the multiple results are combined into point estimates (Rubin, 1996). A critical task in MI is to devise an imputation model (Allison, 2002) or missing data model (Graham, Olchowski, & Gilreath, 2007), which involves specifying the measures that are putatively associated with the missing values. Although this process adds additional steps, the specification of an imputation model and the creation of multiple data sets can produce less-biased estimates in the presence of missing data across a wide variety of data analysis techniques (Schafer, 1997). Besides MI, there are many other methods for addressing missing data (Schafer, 1999; Schafer & Graham, 2002). An equally rigorous method known as direct or full information maximum likelihood (FIML) estimation can produce unbiased estimates and correct standard errors in the presence of missing data. When the number of imputations is sufficiently large, identical missing data models will produce the same estimates under MI and FIML (Graham et al., 2007). Unlike MI, FIML is limited to maximum likelihood analytic techniques and the missing data model must be included in the analysis model. Although we focus on MI, the steps we describe for developing an imputation model are equally appropriate for use in the missing data model for FIML. On the basis of the MI literature, this article describes a framework for developing an imputation model for use with any free or commercial software package that performs MI. BRIEF REVIEW OF MISSING DATA CONCEPTS Generally, both MI and a broad range of missing data issues have received ample attention in the applied literature (Graham et al., 2007). We briefly discuss the three types of distributions that describe the randomness of nonresponse given that this property has consequences for the development of an imputation model. For a discussion of general missing data concepts that are not critical to understanding our discussion of imputation model development, we refer readers to Schafer and Graham (2002). Distribution of Nonresponse The probability distribution of nonresponse--more frequently referred to as the missing data or nonresponse mechanism (Rubin, 1976)--is both an important factor in the decision to impute with MI and a context for the development of an imputation model. …

This letter presents a joint impulsive noise mitigation and sparse channel estimation algorithm for single-carrier systems in mobile underwater acoustic communication (UAC) to address the challenges posed by impulsive noise interference. The basis expansion model (BEM) is introduced to describe the underwater acoustic time-varying channels and reduce the channel parameters to be estimated. Based on the model, the variational Bayesian inference algorithm is employed to derive an iterative estimation expression for jointly estimating the sparse BEM channel coefficients and the impulsive noise. The proposed algorithm mitigates the impact of impulsive noise, leading to enhanced communication reliability. Simulations and sea trials validate the effectiveness of the proposed algorithm, highlighting its potential for practical applications in mobile underwater acoustic communication systems.

Data-driven techniques such as principal component analysis (PCA) have been widely used to derive predictive models from historical data and applied for quality prediction in industry. Motivated by reducing data collinearity and extracting informative driving forces behind data, latent variable models are explored to facilitate the prediction by regressing data on a set of extracted features. In this paper, a novel learning strategy is proposed to build dynamic features under a full Bayesian framework, incorporating data information and prior knowledge of process dynamics. Unlike the traditional PCA that extracts features based on variances explained, in this paper, the latent features are extracted with the guidance of preferred velocities of nominal variations. By applying Bayesian learning algorithms, parameters are estimated with probability distributions accounting for corresponding uncertainties, and the number of latent features can be automatically determined by the variational Bayesian inference algorithm. The effectiveness and practicability of this Bayesian dynamic feature regression are demonstrated through simulated examples as well as an industrial case study.

The application of cognitive radio (CR) technology to the Internet of Things (IoT) network can effectively solve the bottleneck problem of spectrum scarcity. As one of the key steps in cognitive radio-based Internet of Things (CR-IoT), the research over spectrum sensing is of great importance. The utilization of the spectrum resource can be described by the power spectral density (PSD), which can be estimated by the IoT CR nodes cooperatively. The PSD-estimation induced error (PEIE) at each node can decrease the performance of spectrum sensing seriously, but it is often treated as Gaussian distribution easily in the published works, which is not the fact in real systems. This article tries to propose a general modeling method of PEIE to address this problem. After that, an optimization function is constructed over the PSD. Then, the prior model, which can lead to sparsity-inducing penalization terms, is built by introducing two auxiliary parameters to take full advantage of the sparse property. Also, the variational Bayesian inference algorithm using the factor graph is used to find the iterative solution. Finally, compared with the traditional approach, the simulation results demonstrate the superior performance of the proposed algorithm.

In patient follow‐up studies, events of interest may take place between periodic clinical assessments and so the exact time of onset is not observed. Such events are known as “bounded” or “interval‐censored.” Methods for handling such events can be categorized as either (i) applying multiple imputation (MI) strategies or (ii) taking a full likelihood‐based (LB) approach. We focused on MI strategies, rather than LB methods, because of their flexibility. We evaluated MI strategies for bounded event times in a competing risks analysis, examining the extent to which interval boundaries, features of the data distribution and substantive analysis model are accounted for in the imputation model. Candidate imputation models were predictive mean matching (PMM); log‐normal regression with postimputation back‐transformation; normal regression with and without restrictions on the imputed values and Delord and Genin's method based on sampling from the cumulative incidence function. We used a simulation study to compare MI methods and one LB method when data were missing at random and missing not at random, also varying the proportion of missing data, and then applied the methods to a hematopoietic stem cell transplantation dataset. We found that cumulative incidence and median event time estimation were sensitive to model misspecification. In a competing risks analysis, we found that it is more important to account for features of the data distribution than to restrict imputed values based on interval boundaries or to ensure compatibility with the substantive analysis by sampling from the cumulative incidence function. We recommend MI by type 1 PMM.

ObjectivesEpidemiological studies often have missing data, which are commonly handled by multiple imputation (MI). Standard (default) MI procedures use simple linear covariate functions in the imputation model. We examine the bias that may be caused by acceptance of this default option and evaluate methods to identify problematic imputation models, providing practical guidance for researchers. Study Design and SettingUsing simulation and real data analysis, we investigated how imputation model mis-specification affected MI performance, comparing results with complete records analysis (CRA). We considered scenarios in which imputation model mis-specification occurred because (i) the analysis model was mis-specified or (ii) the relationship between exposure and confounder was mis-specified. ResultsMis-specification of the relationship between outcome and exposure, or between exposure and confounder, can cause biased CRA and MI estimates (in addition to any bias in the full-data estimate due to analysis model mis-specification). MI by predictive mean matching can mitigate model mis-specification. Methods for examining model mis-specification were effective in identifying mis-specified relationships. ConclusionWhen using MI methods that assume data are MAR, compatibility between the analysis and imputation models is necessary, but not sufficient to avoid bias. We propose a step-by-step procedure for identifying and correcting mis-specification of imputation models.

Missing data is a common problem in general applied studies, and specially in clinical trials. For implementing sensitivity analysis, several multiple imputation methods exist, like sequential imputation, which restricts to monotone missingness, and Bayesian, where the imputation and analysis models differ, entailing overestimation of variance. Also, full conditional specification provides a conditional interpretation of sensitivity parameters, requiring further calibration to get the desired marginal interpretation. We propose in this paper a multiple imputation procedure, based on a multivariate linear regression model, which keeps compatibility in sensitivity analysis under intermittent missingness, providing a marginal interpretation of the elicited parameters. Simulation studies show that the method behaves well with longitudinal data and remains robust under demanding constraints. We conclude the possibility of situations not covered by the existing methods and well suited for our proposal, which allows more efficient handling of a given multivariate linear regression structure. Its use is illustrated in a real case study, where a sensitivity analysis is accomplished.

Accurate user location tracking is the key to enable location-based services and assist communications in 5 G networks. The massive multiple-input multiple-output (MIMO) technology employed in 5 G networks could potentially provide accurate user localization due to increased spectral efficiency and high directivity. In this paper, we propose an efficient user location tracking algorithm in massive MIMO systems. Firstly, we propose a temporal Markov group-sparse (TMGS) model based on a grid reference to capture the probabilistic temporal correlation and group sparsity of the massive MIMO channels jointly. Then we propose a dynamic variational Bayesian inference (D-VBI) algorithm to handle the TMGS priors under ill-conditioned measurement matrix in the location tracking problem. The proposed D-VBI can jointly recover the user's coarse location in the grid reference and refine the off-grid points to automatically learn the user's exact location to high accuracy. Moreover, the TMGS-based D-VBI algorithm can provide prior information about the user's next location and the possible arriving directions of the future channels to the consecutive time slot to improve the location tracking accuracy. Finally, we verify the superior performance of the proposed location tracking algorithm by extensive simulations.

The usual methods for analyzing case-cohort studies rely on sometimes not fully efficient weighted estimators. Multiple imputation might be a good alternative because it uses all the data available and approximates the maximum partial likelihood estimator. This method is based on the generation of several plausible complete data sets, taking into account uncertainty about missing values. When the imputation model is correctly defined, the multiple imputation estimator is asymptotically unbiased and its variance is correctly estimated. We show that a correct imputation model must be estimated from the fully observed data (cases and controls), using the case status among the explanatory variable. To validate the approach, we analyzed case-cohort studies first with completely simulated data and then with case-cohort data sampled from two real cohorts. The analyses of simulated data showed that, when the imputation model was correct, the multiple imputation estimator was unbiased and efficient. The observed gain in precision ranged from 8 to 37 per cent for phase-1 variables and from 5 to 19 per cent for the phase-2 variable. When the imputation model was misspecified, the multiple imputation estimator was still more efficient than the weighted estimators but it was also slightly biased. The analyses of case-cohort data sampled from complete cohorts showed that even when no strong predictor of the phase-2 variable was available, the multiple imputation was unbiased, as precised as the weighted estimator for the phase-2 variable and slightly more precise than the weighted estimators for the phase-1 variables. However, the multiple imputation estimator was found to be biased when, because of interaction terms, some coefficients of the imputation model had to be estimated from small samples. Multiple imputation is an efficient technique for analyzing case-cohort data. Practically, we suggest building the analysis model using only the case-cohort data and weighted estimators. Multiple imputation can eventually be used to reanalyze the data using the selected model in order to improve the precision of the results.

Propensity score analysis is a popular method to control for confounding in observational studies. A challenge in propensity methods is missing values in confounders. Several strategies for handling missing values exist, but guidance in choosing the best method is needed. In this simulation study, we compared four strategies of handling missing covariate values in propensity matching and propensity weighting. These methods include: complete case analysis, missing indicator method, multiple imputation and combining multiple imputation and missing indicator method. Concurrently, we aimed to provide guidance in choosing the optimal strategy. Simulated scenarios varied regarding missing mechanism, presence of effect modification or unmeasured confounding. Additionally, we demonstrated how missingness graphs help clarifying the missing structure. When no effect modification existed, complete case analysis yielded valid causal treatment effects even when data were missing not at random. In some situations, complete case analysis was also able to partially correct for unmeasured confounding. Multiple imputation worked well if the data were missing (completely) at random, and if the imputation model was correctly specified. In the presence of effect modification, more complex imputation models than default options of commonly used statistical software were required. Multiple imputation may fail when data are missing not at random. Here, combining multiple imputation and the missing indicator method reduced the bias as the missing indicator variable can be a proxy for unobserved confounding. The optimal way to handle missing values in covariates of propensity score models depends on the missing data structure and the presence of effect modification. When effect modification is present, default settings of imputation methods may yield biased results even if data are missing at random.

Multiple imputation and maximum likelihood estimation (via the expectation‐maximization algorithm) are two well‐known methods readily used for analyzing data with missing values. While these two methods are often considered as being distinct from one another, multiple imputation (when using improper imputation) is actually equivalent to a stochastic expectation‐maximization approximation to the likelihood. In this article, we exploit this key result to show that familiar likelihood‐based approaches to model selection, such as Akaike's information criterion (AIC) and the Bayesian information criterion (BIC), can be used to choose the imputation model that best fits the observed data. Poor choice of imputation model is known to bias inference, and while sensitivity analysis has often been used to explore the implications of different imputation models, we show that the data can be used to choose an appropriate imputation model via conventional model selection tools. We show that BIC can be consistent for selecting the correct imputation model in the presence of missing data. We verify these results empirically through simulation studies, and demonstrate their practicality on two classical missing data examples. An interesting result we saw in simulations was that not only can parameter estimates be biased by misspecifying the imputation model, but also by overfitting the imputation model. This emphasizes the importance of using model selection not just to choose the appropriate type of imputation model, but also to decide on the appropriate level of imputation model complexity.

ABSTRACTIntroductionIn analysis of time‐to‐event outcomes, a mixture cure (MC) model is preferred over a standard survival model when the sample includes individuals who will never experience the event of interest. Motivated by a cohort study of breast cancer patients with incomplete biomarkers, we develop multiple imputation (MI) methods assuming a Weibull proportional hazards (PH‐MC) analysis model with multiple prognostic factors. However, for MI with fully conditional specification, an incorrectly specified imputation model can impair accuracy of point and interval estimates.Objectives and MethodsOur goal is to propose imputation models that are compatible with the Weibull PH‐MC analysis models. We derive an exact conditional distribution (ECD) imputation model which involves the analysis model likelihood. Using simulation studies, we compare effect estimate bias and confidence interval (CI) coverage under alternative imputation models including the ECD model, an approximation that includes a cure indicator (cECD), and a comprehensive simple (CS) model. For robust parameter estimation in finite and/or sparse samples, we incorporate the Firth‐type penalized likelihood (FT‐PL) and combined likelihood profile (CLIP) methods into the MI.ResultsCompared to complete case analysis, MI with penalization reduces estimation bias and improves coverage. Although ECD and cECD perform similarly at higher event rates, ECD generates smaller bias and higher coverage at lower rates. CS has larger bias and lower coverage than ECD and cECD, but CIs are narrower than for cECD.ConclusionsIn analyses of biomarkers and composite subtypes for prognosis studies such as in breast cancer, the use of compatible imputation models and penalization methods is recommended for MC modeling in samples with low event numbers and/or with covariate imbalance.

Uncertainty propagation using infinite mixture of Gaussian processes and variational Bayesian inference

Accelerometer data are widely used in research to provide objective measurements of physical activity. Frequently, participants may remove accelerometers during their observation period resulting in missing data referred to as nonwear periods. Common approaches for handling nonwear periods include discarding data (days with insufficient hours or individuals with insufficient valid days) from analyses and single imputation (SI) methods.Purpose:This study evaluates the performance of various discard-, SI-, and multiple imputation (MI)-based approaches on the ability to accurately and precisely characterize the relationship between a summarized measure of accelerometer counts (mean counts per minute) and an outcome (body mass index).Methods:Realistic accelerometer data were simulated under various scenarios that induced nonwear. Data were analyzed using common and MI methods for handling nonwear. Bias, relative standard error, relative mean squared error, and coverage probabilities were compared across methods.Results:MI approaches were superior to commonly applied methods, with bias that ranged from −0.001 to −0.028 that was considerably lower than that of discard-based methods (ranging from −0.050 to −0.057) and SI methods (ranging from −0.061 to −0.081). We also reported substantial variation among MI strategies, with coverage probabilities ranging from .04 to .96.Conclusion:Our findings demonstrate the benefit of applying MI methods over more commonly applied discard- and SI-based approaches. Additionally, we show that how you apply MI matters, where including data from previously observed acceleration measurements in the imputation model when using MI improves model performance.