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.     

A new test for random effects in linear mixed models with longitudinal data

As it is known, testing the existence of random effects is often transferred to testing their zero variances/covariance matrices. It is a nonstandard testing problem because the hypothetical values are on the boundary of the whole space. In the literature, a difference-based test was proposed, which has asymptotically tractable null distribution and is then easy to implement. However, the projection method on which the difference-based test relies may affect and deteriorate its performance when covariates associated with fixed effects and covariates associated with random effects are highly correlated. In the paper, for linear mixed models (LMM) with longitudinal data, a new test is proposed to avoid this problem. The new test is also asymptotically distribution-free and more powerful than the difference-based test, particularly when the above correlation is high. The new test is consistent against all global alternatives and can detect local alternatives converging to the null at a rate as close as to m^−1/2$m^{-1/2}$ with m being the number of subjects. Simulations are carried out to examine the performance and a real data analysis is performed for illustration.     

Review of guidelines and literature for handling missing data in longitudinal clinical trials with a case study

Missing data in clinical trials are inevitable. We highlight the ICH guidelines and CPMP points to consider on missing data. Specifically, we outline how we should consider missing data issues when designing, planning and conducting studies to minimize missing data impact. We also go beyond the coverage of the above two documents, provide a more detailed review of the basic concepts of missing data and frequently used terminologies, and examples of the typical missing data mechanism, and discuss technical details and literature for several frequently used statistical methods and associated software. Finally, we provide a case study where the principles outlined in this paper are applied to one clinical program at protocol design, data analysis plan and other stages of a clinical trial.     

A new mobility index for transition matrices

In this work we construct a mobility index able to grasp the prevailing direction in the evolution of a given set of statistical units. We consider the case of dynamics ruled by a transition matrix, whose states are based on an ordered economic variable (firm size or income, among others) such that the future position of an individual can be better or worse than the current one. The existing indices measure only the absolute value of mobility, without providing information about the main direction in the dynamics. We propose here a whole family of directional indices defined as functions of the transition matrix, so that their absolute value measures the intensity of mobility, and their sign ( $+/-$ + / ? ) represents the prevailing direction towards improvement/worsening in the dynamics under study.     

A flexible link for joint modelling longitudinal and survival data accounting for individual longitudinal heterogeneity

Statistical Methods & Applications - This work aims at jointly modelling longitudinal and survival HIV data by considering the sharing of a set of parameters of interest. For the CD4...     

Multilevel models for longitudinal data

Summary.  Repeated measures and repeated events data have a hierarchical structure which can be analysed by using multilevel models. A growth curve model is an example of a multilevel random-coefficients model, whereas a discrete time event history model for recurrent events can be fitted as a multilevel logistic regression model. The paper describes extensions to the basic growth curve model to handle auto-correlated residuals, multiple-indicator latent variables and correlated growth processes, and event history models for correlated event processes. The multilevel approach to the analysis of repeated measures data is contrasted with structural equation modelling. The methods are illustrated in analyses of children's growth, changes in social and political attitudes, and the interrelationship between partnership transitions and childbearing.     

A martingale residual diagnostic for longitudinal and recurrent event data

One method of assessing the fit of an event history model is to plot the empirical standard deviation of standardised martingale residuals. We develop an alternative procedure which is valid also in the presence of measurement error and applicable to both longitudinal and recurrent event data. Since the covariance between martingale residuals at times t ₀ and t > t ₀ is independent of t, a plot of these covariances should, for fixed t ₀, have no time trend. A test statistic is developed from the increments in the estimated covariances, and we investigate its properties under various types of model misspecification. Applications of the approach are presented using two Brazilian studies measuring daily prevalence and incidence of infant diarrhoea and a longitudinal study into treatment of schizophrenia.     

A Bayesian model for longitudinal count data with non-ignorable dropout

Asthma is an important chronic disease of childhood. An intervention programme for managing asthma was designed on principles of self-regulation and was evaluated by a randomized longitudinal study.The study focused on several outcomes, and, typically, missing data remained a pervasive problem. We develop a pattern-mixture model to evaluate the outcome of intervention on the number of hospitalizations with non-ignorable dropouts. Pattern-mixture models are not generally identifiable as no data may be available to estimate a number of model parameters. Sensitivity analyses are performed by imposing structures on the unidentified parameters.We propose a parameterization which permits sensitivity analyses on clustered longitudinal count data that have missing values due to non-ignorable missing data mechanisms. This parameterization is expressed as ratios between event rates across missing data patterns and the observed data pattern and thus measures departures from an ignorable missing data mechanism. Sensitivity analyses are performed within a Bayesian framework by averaging over different prior distributions on the event ratios. This model has the advantage of providing an intuitive and flexible framework for incorporating the uncertainty of the missing data mechanism in the final analysis.     

Generalized additive models for longitudinal data

We introduce a class of models for longitudinal data by extending the generalized estimating equations approach of Liang and Zeger (1986) to incorporate the flexibility of nonparametric smoothing. The algorithm provides a unified estimation procedure for marginal distributions from the exponential family. We propose pointwise standard-error bands and approximate likelihood-ratio and score tests for inference. The algorithm is formally derived by using the penalized quasilikelihood framework. Convergence of the estimating equations and consistency of the resulting solutions are discussed. We illustrate the algorithm with data on the population dynamics of Colorado potato beetles on potato plants.     

A robust approach to longitudinal data analysis

The author introduces robust techniques for estimation, inference and variable selection in the analysis of longitudinal data. She first addresses the problem of the robust estimation of the regression and nuisance parameters, for which she derives the asymptotic distribution. She uses weighted estimating equations to build robust quasi‐likelihood functions. These functions are then used to construct a class of test statistics for variable selection. She derives the limiting distribution of these tests and shows its robustness properties in terms of stability of the asymptotic level and power under contamination. An application to a real data set allows her to illustrate the benefits of a robust analysis.     

Multiple-index varying-coefficient models for longitudinal data

In haemodialysis patients, vascular access type is of paramount importance. Although recent studies have found that central venous catheter is often associated with poor outcomes and switching to arteriovenous fistula is beneficial, studies have not fully elucidated how the effect of switching of access on outcomes changes over time for patients on dialysis and whether the effect depends on switching time. In this paper, we characterise the switching access type effect on outcomes for haemodialysis patients. This is achieved by using a new class of multiple-index varying-coefficient (MIVC) models. We develop a new estimation procedure for MIVC models based on local linear, profile least-square method and Cholesky decomposition. Monte Carlo simulation studies show excellent finite sample performance. Finally, we analyse the dialysis data using our method.     

A class of shrinkage priors for the dependence structure in longitudinal data

We review a general class of priors for the dependence in longitudinal (temporal) data in settings where a parametric form is often assumed and place them in the context of the literature. The idea is to embed priors on the parameters of the structure within a richer, more flexible class of priors. These priors are shown to contain standard objective priors for structured and unstructured dependence models as special cases under certain conditions and parameterizations. Recommendations and specific details regarding their use are provided.     

A semiparametric stochastic mixed effects model for bivariate cyclic longitudinal data

We propose a flexible semiparametric stochastic mixed effects model for bivariate cyclic longitudinal data. The model can handle either single cycle or, more generally, multiple consecutive cycle data. The approach models the mean of responses by parametric fixed effects and a smooth nonparametric function for the underlying time effects, and the relationship across the bivariate responses by a bivariate Gaussian random field and a joint distribution of random effects. The proposed model not only can model complicated individual profiles, but also allows for more flexible within-subject and between-response correlations. The fixed effects regression coefficients and the nonparametric time functions are estimated using maximum penalized likelihood, where the resulting estimator for the nonparametric time function is a cubic smoothing spline. The smoothing parameters and variance components are estimated simultaneously using restricted maximum likelihood. Simulation results show that the parameter estimates are close to the true values. The fit of the proposed model on a real bivariate longitudinal dataset of pre-menopausal women also performs well, both for a single cycle analysis and for a multiple consecutive cycle analysis. The Canadian Journal of Statistics 48: 471–498; 2020 © 2020 Statistical Society of Canada     

A zero-augmented gamma mixed model for longitudinal data with many zeros

In many occupational safety interventions, the objective is to reduce the injury incidence as well as the mean claims cost once injury has occurred. The claims cost data within a period typically contain a large proportion of zero observations (no claim). The distribution thus comprises a point mass at 0 mixed with a non-degenerate parametric component. Essentially, the likelihood function can be factorized into two orthogonal components. These two components relate respectively to the effect of covariates on the incidence of claims and the magnitude of claims, given that claims are made. Furthermore, the longitudinal nature of the intervention inherently imposes some correlation among the observations. This paper introduces a zero-augmented gamma random effects model for analysing longitudinal data with many zeros. Adopting the generalized linear mixed model (GLMM) approach reduces the original problem to the fitting of two independent GLMMs. The method is applied to evaluate the effectiveness of a workplace risk assessment teams program, trialled within the cleaning services of a Western Australian public hospital.     

A new way to order independent components

A relatively newer computational technique adopted by statisticians is known as independent component analysis (ICA) which is used to analyze complex multidimensional data with the objective to separate it into components that are independent to each other. Quite often the main interest for conducting ICA is to identify a small number of significant independent components (ICs) to replace the original complex dimensions with. For this, determining the order of identified ICs is a pre-requisite. The area is not unaddressed but it does deserve a careful revisiting. This is the subject matter of the paper which introduces a new method to order ICs. The proposed method is based upon regression approach. It compares the magnitude of the mixing coefficients and regression coefficients of the regression of the original series on ICs. Their compatibility determines the order.     

A robust pairwise likelihood method for incomplete longitudinal binary data arising in clusters

Clustered longitudinal data feature cross‐sectional associations within clusters, serial dependence within subjects, and associations between responses at different time points from different subjects within the same cluster. Generalized estimating equations are often used for inference with data of this sort since they do not require full specification of the response model. When data are incomplete, however, they require data to be missing completely at random unless inverse probability weights are introduced based on a model for the missing data process. The authors propose a robust approach for incomplete clustered longitudinal data using composite likelihood. Specifically, pairwise likelihood methods are described for conducting robust estimation with minimal model assumptions made. The authors also show that the resulting estimates remain valid for a wide variety of missing data problems including missing at random mechanisms and so in such cases there is no need to model the missing data process. In addition to describing the asymptotic properties of the resulting estimators, it is shown that the method performs well empirically through simulation studies for complete and incomplete data. Pairwise likelihood estimators are also compared with estimators obtained from inverse probability weighted alternating logistic regression. An application to data from the Waterloo Smoking Prevention Project is provided for illustration. The Canadian Journal of Statistics 39: 34–51; 2011 © 2010 Statistical Society of Canada     

Models for longitudinal data with censored changepoints

Summary.  In longitudinal studies of biological markers, different individuals may have different underlying patterns of response. In some applications, a subset of individuals experiences latent events, causing an instantaneous change in the level or slope of the marker trajectory. The paper presents a general mixture of hierarchical longitudinal models for serial biomarkers. Interest centres both on the time of the event and on levels of the biomarker before and after the event. In observational studies where marker series are incomplete, the latent event can be modelled by a survival distribution. Risk factors for the occurrence of the event can be investigated by including covariates in the survival distribution. A combination of Gibbs, Metropolis–Hastings and reversible jump Markov chain Monte Carlo sampling is used to fit the models to serial measurements of forced expiratory volume from lung transplant recipients.     

A simple approach to analyzing clustered longitudinal data

When modeling correlated binary data in the presence of informative cluster sizes, generalized estimating equations with either resampling or inverse-weighting, are often used to correct for estimation bias. However, existing methods for the clustered longitudinal setting assume constant cluster sizes over time. We present a subject-weighted generalized estimating equations scheme that provides valid parameter estimation for the clustered longitudinal setting while allowing cluster sizes to change over time. We compare, via simulation, the performance of existing methods to our subject-weighted approach. The subject-weighted approach was the only method that showed negligible bias, with excellent coverage, for all model parameters.     

Bayesian quantile regression for longitudinal data models

In this paper, we discuss a fully Bayesian quantile inference using Markov Chain Monte Carlo (MCMC) method for longitudinal data models with random effects. Under the assumption of error term subject to asymmetric Laplace distribution, we establish a hierarchical Bayesian model and obtain the posterior distribution of unknown parameters at τ-th level. We overcome the current computational limitations using two approaches. One is the general MCMC technique with Metropolis–Hastings algorithm and another is the Gibbs sampling from the full conditional distribution. These two methods outperform the traditional frequentist methods under a wide array of simulated data models and are flexible enough to easily accommodate changes in the number of random effects and in their assumed distribution. We apply the Gibbs sampling method to analyse a mouse growth data and some different conclusions from those in the literatures are obtained.