Hybrid pairwise‐likelihood estimation methods for incomplete longitudinal binary data

In longitudinal data, missing observations occur commonly with incomplete responses and covariates. Missing data can have a ‘missing not at random’ mechanism, a non‐monotone missing pattern, and moreover response and covariates can be missing not simultaneously. To avoid complexities in both modelling and computation, a two‐stage estimation method and a pairwise‐likelihood method are proposed. The two‐stage estimation method enjoys simplicities in computation, but incurs more severe efficiency loss. On the other hand, the pairwise approach leads to estimators with better efficiency, but can be cumbersome in computation. In this paper, we develop a compromise method using a hybrid pairwise‐likelihood framework. Our proposed approach has better efficiency than the two‐stage method, but its computational cost is still reasonable compared to the pairwise approach. The performance of the methods is evaluated empirically by means of simulation studies. Our methods are used to analyse longitudinal data obtained from the National Population Health Study.     

Conjugate analysis of multivariate normal data with incomplete observations

The authors discuss prior distributions that are conjugate to the multivariate normal likelihood when some of the observations are incomplete. They present a general class of priors for incorporating information about unidentified parameters in the covariance matrix. They analyze the special case of monotone patterns of missing data, providing an explicit recursive form for the posterior distribution resulting from a conjugate prior distribution. They develop an importance sampling and a Gibbs sampling approach to sample from a general posterior distribution and compare the two methods.     

A comparison of various software tools for dealing with missing data via imputation

In real-life situations, we often encounter data sets containing missing observations. Statistical methods that address missingness have been extensively studied in recent years. One of the more popular approaches involves imputation of the missing values prior to the analysis, thereby rendering the data complete. Imputation broadly encompasses an entire scope of techniques that have been developed to make inferences about incomplete data, ranging from very simple strategies (e.g. mean imputation) to more advanced approaches that require estimation, for instance, of posterior distributions using Markov chain Monte Carlo methods. Additional complexity arises when the number of missingness patterns increases and/or when both categorical and continuous random variables are involved. Implementation of routines, procedures, or packages capable of generating imputations for incomplete data are now widely available. We review some of these in the context of a motivating example, as well as in a simulation study, under two missingness mechanisms (missing at random and missing not at random). Thus far, evaluation of existing implementations have frequently centred on the resulting parameter estimates of the prescribed model of interest after imputing the missing data. In some situations, however, interest may very well be on the quality of the imputed values at the level of the individual – an issue that has received relatively little attention. In this paper, we focus on the latter to provide further insight about the performance of the different routines, procedures, and packages in this respect.     

Application of sensitivity analysis to incomplete longitudinal CD4 count data

In this paper, we investigate the effect of tuberculosis pericarditis (TBP) treatment on CD4 count changes over time and draw inferences in the presence of missing data. We accounted for missing data and conducted sensitivity analyses to assess whether inferences under missing at random (MAR) assumption are sensitive to not missing at random (NMAR) assumptions using the selection model (SeM) framework. We conducted sensitivity analysis using the local influence approach and stress-testing analysis. Our analyses showed that the inferences from the MAR are robust to the NMAR assumption and influential subjects do not overturn the study conclusions about treatment effects and the dropout mechanism. Therefore, the missing CD4 count measurements are likely to be MAR. The results also revealed that TBP treatment does not interact with HIV/AIDS treatment and that TBP treatment has no significant effect on CD4 count changes over time. Although the methods considered were applied to data in the IMPI trial setting, the methods can also be applied to clinical trials with similar settings.     

Bias from the use of generalized estimating equations to analyze incomplete longitudinal binary data

Patient dropout is a common problem in studies that collect repeated binary measurements. Generalized estimating equations (GEE) are often used to analyze such data. The dropout mechanism may be plausibly missing at random (MAR), i.e. unrelated to future measurements given covariates and past measurements. In this case, various authors have recommended weighted GEE with weights based on an assumed dropout model, or an imputation approach, or a doubly robust approach based on weighting and imputation. These approaches provide asymptotically unbiased inference, provided the dropout or imputation model (as appropriate) is correctly specified. Other authors have suggested that, provided the working correlation structure is correctly specified, GEE using an improved estimator of the correlation parameters (‘modified GEE’) show minimal bias. These modified GEE have not been thoroughly examined. In this paper, we study the asymptotic bias under MAR dropout of these modified GEE, the standard GEE, and also GEE using the true correlation. We demonstrate that all three methods are biased in general. The modified GEE may be preferred to the standard GEE and are subject to only minimal bias in many MAR scenarios but in others are substantially biased. Hence, we recommend the modified GEE be used with caution.     

Joint regression modeling for missing categorical covariates in generalized linear models

Missing covariates data is a common issue in generalized linear models (GLMs). A model-based procedure arising from properly specifying joint models for both the partially observed covariates and the corresponding missing indicator variables represents a sound and flexible methodology, which lends itself to maximum likelihood estimation as the likelihood function is available in computable form. In this paper, a novel model-based methodology is proposed for the regression analysis of GLMs when the partially observed covariates are categorical. Pair-copula constructions are used as graphical tools in order to facilitate the specification of the high-dimensional probability distributions of the underlying missingness components. The model parameters are estimated by maximizing the weighted log-likelihood function by using an EM algorithm. In order to compare the performance of the proposed methodology with other well-established approaches, which include complete-cases and multiple imputation, several simulation experiments of Binomial, Poisson and Normal regressions are carried out under both missing at random and non-missing at random mechanisms scenarios. The methods are illustrated by modeling data from a stage III melanoma clinical trial. The results show that the methodology is rather robust and flexible, representing a competitive alternative to traditional techniques.     

A semi-parametric estimation of a survival function from incomplete and doubly censored data

The purpose of this paper is to present a semi-parametric estimation of a survival function when analyzing incomplete and doubly censored data. Under the assumption that the chance of censoring is not related to the individual's survivorship, we propose a consistent estimation of survival. The derived estimator treats the uncensored observations nonparametrically and uses parametric models for both right and left censored data. Some asymptotic properties and simulation studies are also presented in order to analyze the behavior of the proposed estimator.     

Incomplete categorical data analysis: a bayesian perspective

In this paper the Bayesian analysis of incomplete categorical data under informative general censoring proposed by Paulino and Pereira (1995) is revisited. That analysis is based on Dirichlet priors and can be applied to any missing data pattern. However, the known properties of the posterior distributions are scarce and therefore severe limitations to the posterior computations remain. Here is shown how a Monte Carlo simulation approach based on an alternative parameterisation can be used to overcome the former computational difficulties. The proposed simulation approach makes available the approximate estimation of general parametric functions and can be implemented in a very straightforward way.     

Jointly modeling skew longitudinal survival data with missingness and mismeasured covariates

Jointly modeling longitudinal and survival data has been an active research area. Most researches focus on improving the estimating efficiency but ignore many data features frequently encountered in practice. In the current study, we develop the joint models that concurrently accounting for longitudinal and survival data with multiple features. Specifically, the proposed model handles skewness, missingness and measurement errors in covariates which are typically observed in the collection of longitudinal survival data from many studies. We employ a Bayesian inferential method to make inference on the proposed model. We applied the proposed model to an real data study. A few alternative models under different conditions are compared. We conduct extensive simulations in order to evaluate how the method works.     

Bias correction in logistic regression with missing categorical covariates

Logistic regression plays an important role in many fields. In practice, we often encounter missing covariates in different applied sectors, particularly in biomedical sciences. Ibrahim (1990) proposed a method to handle missing covariates in generalized linear model (GLM) setup. It is well known that logistic regression estimates using small or medium sized missing data are biased. Considering the missing data that are missing at random, in this paper we have reduced the bias by two methods; first we have derived a closed form bias expression using Cox and Snell (1968), and second we have used likelihood based modification similar to Firth (1993). Here we have analytically shown that the Firth type likelihood modification in Ibrahim led to the second order bias reduction. The proposed methods are simple to apply on an existing method, need no analytical work, with the exception of a little change in the optimization function. We have carried out extensive simulation studies comparing the methods, and our simulation results are also supported by a real world data.     

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.     

Data-driven sensitivity analysis to detect missing data mechanism with applications to structural equation modelling

Missing data are a common problem in almost all areas of empirical research. Ignoring the missing data mechanism, especially when data are missing not at random (MNAR), can result in biased and/or inefficient inference. Because MNAR mechanism is not verifiable based on the observed data, sensitivity analysis is often used to assess it. Current sensitivity analysis methods primarily assume a model for the response mechanism in conjunction with a measurement model and examine sensitivity to missing data mechanism via the parameters of the response model. Recently, Jamshidian and Mata (Post-modelling sensitivity analysis to detect the effect of missing data mechanism, Multivariate Behav. Res. 43 (2008), pp. 432–452) introduced a new method of sensitivity analysis that does not require the difficult task of modelling the missing data mechanism. In this method, a single measurement model is fitted to all of the data and to a sub-sample of the data. Discrepancy in the parameter estimates obtained from the the two data sets is used as a measure of sensitivity to missing data mechanism. Jamshidian and Mata describe their method mainly in the context of detecting data that are missing completely at random (MCAR). They used a bootstrap type method, that relies on heuristic input from the researcher, to test for the discrepancy of the parameter estimates. Instead of using bootstrap, the current article obtains confidence interval for parameter differences on two samples based on an asymptotic approximation. Because it does not use bootstrap, the developed procedure avoids likely convergence problems with the bootstrap methods. It does not require heuristic input from the researcher and can be readily implemented in statistical software. The article also discusses methods of obtaining sub-samples that may be used to test missing at random in addition to MCAR. An application of the developed procedure to a real data set, from the first wave of an ongoing longitudinal study on aging, is presented. Simulation studies are performed as well, using two methods of missing data generation, which show promise for the proposed sensitivity method. One method of missing data generation is also new and interesting in its own right.     

Variable selection for longitudinal data with high-dimensional covariates and dropouts

A new variable selection approach utilizing penalized estimating equations is developed for high-dimensional longitudinal data with dropouts under a missing at random (MAR) mechanism. The proposed method is based on the best linear approximation of efficient scores from the full dataset and does not need to specify a separate model for the missing or imputation process. The coordinate descent algorithm is adopted to implement the proposed method and is computational feasible and stable. The oracle property is established and extensive simulation studies show that the performance of the proposed variable selection method is much better than that of penalized estimating equations dealing with complete data which do not account for the MAR mechanism. In the end, the proposed method is applied to a Lifestyle Education for Activity and Nutrition study and the interaction effect between intervention and time is identified, which is consistent with previous findings.     

On estimation of frequency data with censored observations

The problem of the estimation of mean frequency of events in the presence of censoring is important in assessing the efficacy, safety and cost of therapies. The mean frequency is typically estimated by dividing the total number of events by the total number of patients under study. This method, referred to in this paper as the ‘naïve estimator’, ignores the censoring. Other approaches available for this problem require many assumptions that are rarely acceptable. These include the assumption of independence, constant hazard rate over time and other similar distributional assumptions. In this paper a simple non‐parametric estimator based on the sum of the products of Kaplan–Meier estimators is proposed as an estimator of mean frequency, and its approximate variance and standard error are derived. An illustration is provided to show the derivation of the proposed estimator. Although the clinical trial setting is used in this paper, the problem has applications in other areas where survival analysis is used and recurrent events are studied. Copyright © 2003 John Wiley & Sons, Ltd.     

Weighted empirical likelihood for quantile regression with non ignorable missing covariates

In this paper, we propose an empirical likelihood-based weighted estimator of regression parameter in quantile regression model with non ignorable missing covariates. The proposed estimator is computationally simple and achieves semiparametric efficiency if the probability of missingness on the fully observed variables is correctly specified. The efficiency gain of the proposed estimator over the complete-case-analysis estimator is quantified theoretically and illustrated via simulation and a real data application.     

Empirical likelihood for single index model with missing covariates at random

In this paper, we investigate the empirical-likelihood-based inference for the construction of confidence intervals and regions of the parameters of interest in single index models with missing covariates at random. An augmented inverse probability weighted-type empirical likelihood ratio for the parameters of interest is defined such that this ratio is asymptotically standard chi-squared. Our approach is to directly calibrate the empirical log-likelihood ratio, and does not need multiplication by an adjustment factor for the original ratio. Our bias-corrected empirical likelihood is self-scale invariant and no plug-in estimator for the limiting variance is needed. Some simulation studies are carried out to assess the performance of our proposed method.     

A skew-normal random effects model for longitudinal ordinal categorical responses with missing data

Missing values are common in longitudinal data studies. The missing data mechanism is termed non-ignorable (NI) if the probability of missingness depends on the non-response (missing) observations. This paper presents a model for the ordinal categorical longitudinal data with NI non-monotone missing values. We assumed two separate models for the response and missing procedure. The response is modeled as ordinal logistic, whereas the logistic binary model is considered for the missing process. We employ these models in the context of so-called shared-parameter models, where the outcome and missing data models are connected by a common set of random effects. It is commonly assumed that the random effect follows the normal distribution in longitudinal data with or without missing data. This can be extremely restrictive in practice, and it may result in misleading statistical inferences. In this paper, we instead adopt a more flexible alternative distribution which is called the skew-normal distribution. The methodology is illustrated through an application to Schizophrenia Collaborative Study data [19 D. Hedeker, Generalized linear mixed models, in Encyclopedia of Statistics in Behavioral Science, B. Everitt and D. Howell, eds., John Wiley, London, 2005, pp. 729–738. [Google Scholar]] and a simulation.     

Linear Increments with Non‐monotone Missing Data and Measurement Error

Linear increments (LI) are used to analyse repeated outcome data with missing values. Previously, two LI methods have been proposed, one allowing non‐monotone missingness but not independent measurement error and one allowing independent measurement error but only monotone missingness. In both, it was suggested that the expected increment could depend on current outcome. We show that LI can allow non‐monotone missingness and either independent measurement error of unknown variance or dependence of expected increment on current outcome but not both. A popular alternative to LI is a multivariate normal model ignoring the missingness pattern. This gives consistent estimation when data are normally distributed and missing at random (MAR). We clarify the relation between MAR and the assumptions of LI and show that for continuous outcomes multivariate normal estimators are also consistent under (non‐MAR and non‐normal) assumptions not much stronger than those of LI. Moreover, when missingness is non‐monotone, they are typically more efficient.     

Marginal methods for clustered longitudinal binary data with incomplete covariates

Many analyses for incomplete longitudinal data are directed to examining the impact of covariates on the marginal mean responses. We consider the setting in which longitudinal responses are collected from individuals nested within clusters. We discuss methods for assessing covariate effects on the mean and association parameters when covariates are incompletely observed. Weighted first and second order estimating equations are constructed to obtain consistent estimates of mean and association parameters when covariates are missing at random. Empirical studies demonstrate that estimators from the proposed method have negligible finite sample biases in moderate samples. An application to the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) demonstrates the utility of the proposed method.