Different methods for handling incomplete longitudinal binary outcome due to missing at random dropout

This paper compares the performance of weighted generalized estimating equations (WGEEs), multiple imputation based on generalized estimating equations (MI-GEEs) and generalized linear mixed models (GLMMs) for analyzing incomplete longitudinal binary data when the underlying study is subject to dropout. The paper aims to explore the performance of the above methods in terms of handling dropouts that are missing at random (MAR). The methods are compared on simulated data. The longitudinal binary data are generated from a logistic regression model, under different sample sizes. The incomplete data are created for three different dropout rates. The methods are evaluated in terms of bias, precision and mean square error in case where data are subject to MAR dropout. In conclusion, across the simulations performed, the MI-GEE method performed better in both small and large sample sizes. Evidently, this should not be seen as formal and definitive proof, but adds to the body of knowledge about the methods’ relative performance. In addition, the methods are compared using data from a randomized clinical trial.     

Marginal and association regression models for longitudinal binary data with drop‐outs: A likelihood‐based approach

Longitudinal data often contain missing observations, and it is in general difficult to justify particular missing data mechanisms, whether random or not, that may be hard to distinguish. The authors describe a likelihood‐based approach to estimating both the mean response and association parameters for longitudinal binary data with drop‐outs. They specify marginal and dependence structures as regression models which link the responses to the covariates. They illustrate their approach using a data set from the Waterloo Smoking Prevention Project They also report the results of simulation studies carried out to assess the performance of their technique under various circumstances.     

Two-step estimation of functional linear models with applications to longitudinal data

Functional linear models are useful in longitudinal data analysis. They include many classical and recently proposed statistical models for longitudinal data and other functional data. Recently, smoothing spline and kernel methods have been proposed for estimating their coefficient functions nonparametrically but these methods are either intensive in computation or inefficient in performance. To overcome these drawbacks, in this paper, a simple and powerful two-step alternative is proposed. In particular, the implementation of the proposed approach via local polynomial smoothing is discussed. Methods for estimating standard deviations of estimated coefficient functions are also proposed. Some asymptotic results for the local polynomial estimators are established. Two longitudinal data sets, one of which involves time-dependent covariates, are used to demonstrate the approach proposed. Simulation studies show that our two-step approach improves the kernel method proposed by Hoover and co-workers in several aspects such as accuracy, computational time and visual appeal of the estimators.     

Modification of GEE1 and linear mixed-effects models for heteroscedastic longitudinal Gaussian data

A characterization of GLMs is given. Modification of the Gaussian GEE1, modified GEE1, was applied to heteroscedastic longitudinal data, to which linear mixed-effects models are usually applied. The modified GEE1 models scale multivariate data to homoscedastic data maintaining the correlation structure and apply usual GEE1 to homoscedastic data, which needs no-diagnostics for diagonal variances. Relationships among multivariate linear regression methods, ordinary/generalized LS, naïve/modified GEE1, and linear mixed-effects models were discussed. An application showed modified GEE1 gave most efficient parameter estimation. Correct specification of the main diagonals of heteroscedastic data variance appears to be more important for efficient mean parameter estimation.     

Markov structure based logistic regression for repeated measures: An application to diabetes mellitus data

In longitudinal studies, as repeated observations are made on the same individual the response variables will usually be correlated. In analyzing such data, this dependence must be taken into account to avoid misleading inferences. The focus of this paper is to apply a logistic marginal model with Markovian dependence proposed by Azzalini [A. Azzalini, Logistic regression for autocorrelated data with application to repeated measures, Biometrika 81 (1994) 767–775] to the study of the influence of time-dependent covariates on the marginal distribution of the binary response in serially correlated binary data. We have shown how to construct the model so that the covariates relate only to the mean value of the process, independent of the association parameters. After formulating the proposed model for repeated measures data, the same approach is applied to missing data. An application is provided to the diabetes mellitus data of registered patients at the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) in 1984, using both time stationary and time varying covariates.     

Exact methods of testing the homogeneity of prevalences for correlated binary data

Correlated binary data arise in many ophthalmological and otolaryngological clinical trials. To test the homogeneity of prevalences among different groups is an important issue when conducting these trials. The equal correlation coefficients model proposed by Donner in 1989 is a popular model handling correlated binary data. The asymptotic chi-square test works well when the sample size is large. However, it would fail to maintain the type I error rate when the sample size is relatively small. In this paper, we propose several exact methods to deal with small sample scenarios. Their performances are compared with respect to type I error rate and power. The ‘M approach’ and the ‘E + M approach’ seem to outperform the others. A real work example is given to further explain how these approaches work. Finally, the computational efficiency of the exact methods is discussed as a pressing issue of future work.     

Estimation of multi-state models with missing covariate values based on observed data likelihood

Abstract

Continuous-time multi-state models are commonly used to study diseases with multiple stages. Potential risk factors associated with the disease are added to the transition intensities of the model as covariates, but missing covariate measurements arise frequently in practice. We propose a likelihood-based method that deals efficiently with a missing covariate in these models. Our simulation study showed that the method performs well for both “missing completely at random” and “missing at random” mechanisms. We also applied our method to a real dataset, the Einstein Aging Study.     

Influence of human immunodeficiency virus infection on neurological impairment: an analysis of longitudinal binary data with informative drop-out

A study to investigate the human immunodeficiency virus (HIV) status on the course of neurological impairment, conducted by the HIV Center at Columbia University, followed a cohort of HIV positive and negative gay men for 5 years and assessed the presence or absence of neurological impairment every 6 months. Almost half of the subjects dropped out before the end of the study for reasons that might have been related to the missing neurological data. We propose likelihood-based methods for analysing such binary longitudinal data under informative and non-informative drop-out. A transition model is assumed for the binary response, and several models for the drop-out processes are considered which are functions of the response variable (neurological impairment). The likelihood ratio test is used to compare models with informative and non-informative drop-out mechanisms. Using simulations, we investigate the percentage bias and mean-squared error (MSE) of the parameter estimates in the transition model under various assumptions for the drop-out. We find evidence for informative drop-out in the study, and we illustrate that the bias and MSE for the parameters of the transition model are not directly related to the observed drop-out or missing data rates. The effect of HIV status on the neurological impairment is found to be statistically significant under each of the models considered for the drop-out, although the regression coefficient may be biased in certain cases. The presence and relative magnitude of the bias depend on factors such as the probability of drop-out conditional on the presence of neurological impairment and the prevalence of neurological impairment in the population under study.     

A longitudinal study of children's aggressive behaviours based on multivariate mixed models with incomplete data

The authors consider children's behavioural and emotional problems and their relationships with possible predictors. They propose a multivariate transitional mixed‐effects model for a longitudinal study and simultaneously address non‐ignorable missing data in responses and covariates, measurement errors in covariates, and multivariate modelling of the responses and covariate processes. A real dataset is analysed in details using the proposed method with some interesting results. The Canadian Journal of Statistics 37: 435–452; 2009 © 2009 Statistical Society of Canada     

Assessing goodness-of-fit of categorical regression models based on case-control data

Demonstrated equivalence between a categorical regression model based on case‐control data and an I‐sample semiparametric selection bias model leads to a new goodness‐of‐fit test. The proposed test statistic is an extension of an existing Kolmogorov–Smirnov‐type statistic and is the weighted average of the absolute differences between two estimated distribution functions in each response category. The paper establishes an optimal property for the maximum semiparametric likelihood estimator of the parameters in the I‐sample semiparametric selection bias model. It also presents a bootstrap procedure, some simulation results and an analysis of two real datasets.     

A monte carlo evaluation of response surface analysis based on paired-comparison data

The use of the logit transformation on paired-comparison data in the weighted least squares analysis of response surfaces for aesthetic qualities of products is discussed. Monte Carlo simulations are employed to investigate the small sample properties of the estimators and test statistics. A secondary objective of the Monte Carlo simulations is the comparison of two transformation procedures. The simulations are of standard-item paired-compar-ison experiments in which ties are not allowed.     

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.