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Bayesian semiparametric nonlinear mixed-effects joint models for data with skewness, missing responses, and measurement errors in covariates.

ABSTRACT: It is a common practice to analyze complex longitudinal data using semiparametric nonlinear mixed-effects (SNLME) models with a normal distribution. Normality assumption of model errors may unrealistically obscure important features of subject variations. To partially explain between- and within-subject variations, covariates are usually introduced in such models, but some covariates may often be measured with substantial errors. Moreover, the responses may be missing and the missingness may be nonignorable. Inferential procedures can be complicated dramatically when data with skewness, missing values, and measurement error are observed. In the literature, there has been considerable interest in accommodating either skewness, incompleteness or covariate measurement error in such models, but there has been relatively little study concerning all three features simultaneously. In this article, our objective is to address the simultaneous impact of skewness, missingness, and covariate measurement error by jointly modeling the response and covariate processes based on a flexible Bayesian SNLME model. The method is illustrated using a real AIDS data set to compare potential models with various scenarios and different distribution specifications.

SUBMITTER: Huang Y

PROVIDER: S-EPMC3460696 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Bayesian semiparametric nonlinear mixed-effects joint models for data with skewness, missing responses, and measurement errors in covariates.

Huang Yangxin Y Dagne Getachew G

Biometrics 20111207 3

It is a common practice to analyze complex longitudinal data using semiparametric nonlinear mixed-effects (SNLME) models with a normal distribution. Normality assumption of model errors may unrealistically obscure important features of subject variations. To partially explain between- and within-subject variations, covariates are usually introduced in such models, but some covariates may often be measured with substantial errors. Moreover, the responses may be missing and the missingness may be ...[more]

PMID: 22150787

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Project description:BackgroundIn clinical trials and epidemiological research, mixed-effects models are commonly used to examine population-level and subject-specific trajectories of biomarkers over time. Despite their increasing popularity and application, the specification of these models necessitates a great deal of care when analysing longitudinal data with non-linear patterns and asymmetry. Parametric (linear) mixed-effect models may not capture these complexities flexibly and adequately. Additionally, assuming a Gaussian distribution for random effects and/or model errors may be overly restrictive, as it lacks robustness against deviations from symmetry.MethodsThis paper presents a semiparametric mixed-effects model with flexible distributions for complex longitudinal data in the Bayesian paradigm. The non-linear time effect on the longitudinal response was modelled using a spline approach. The multivariate skew-t distribution, which is a more flexible distribution, is utilized to relax the normality assumptions associated with both random-effects and model errors.ResultsTo assess the effectiveness of the proposed methods in various model settings, simulation studies were conducted. We then applied these models on chronic kidney disease (CKD) data and assessed the relationship between covariates and estimated glomerular filtration rate (eGFR). First, we compared the proposed semiparametric partially linear mixed-effect (SPPLM) model with the fully parametric one (FPLM), and the results indicated that the SPPLM model outperformed the FPLM model. We then further compared four different SPPLM models, each assuming different distributions for the random effects and model errors. The model with a skew-t distribution exhibited a superior fit to the CKD data compared to the Gaussian model. The findings from the application revealed that hypertension, diabetes, and follow-up time had a substantial association with kidney function, specifically leading to a decrease in GFR estimates.ConclusionsThe application and simulation studies have demonstrated that our work has made a significant contribution towards a more robust and adaptable methodology for modeling intricate longitudinal data. We achieved this by proposing a semiparametric Bayesian modeling approach with a spline smoothing function and a skew-t distribution.

Dataset Information

Bayesian semiparametric nonlinear mixed-effects joint models for data with skewness, missing responses, and measurement errors in covariates.

Publications

Bayesian semiparametric nonlinear mixed-effects joint models for data with skewness, missing responses, and measurement errors in covariates.

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