A generalized Bayesian nonlinear mixed‐effects regression model for zero‐inflated longitudinal count data in tuberculosis trials

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Authors

Burger, Divan Aristo
Schall, Robert
Jacobs, Rianne
Chen, Ding-Geng (Din)

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Wiley

Abstract

In this paper, we investigate Bayesian generalized nonlinear mixed‐effects (NLME) regression models for zero‐inflated longitudinal count data. The methodology is motivated by and applied to colony forming unit (CFU) counts in extended bactericidal activity tuberculosis (TB) trials. Furthermore, for model comparisons, we present a generalized method for calculating the marginal likelihoods required to determine Bayes factors. A simulation study shows that the proposed zero‐inflated negative binomial regression model has good accuracy, precision, and credibility interval coverage. In contrast, conventional normal NLME regression models applied to log‐transformed count data, which handle zero counts as left censored values, may yield credibility intervals that undercover the true bactericidal activity of anti‐TB drugs. We therefore recommend that zero‐inflated NLME regression models should be fitted to CFU count on the original scale, as an alternative to conventional normal NLME regression models on the logarithmic scale.

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Keywords

Nonlinear mixed‐effects (NLME), Colony forming unit (CFU), Tuberculosis (TB), Bayesian, Bactericidal activity, Longitudinal, Mixed‐effects, Zero inflated, Bactericidal activity, Sterilizing activity, Poisson, Pyrazinamide, Moxifloxacin, Combination, Pretomanid (PA‐824), Inference, Culture

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Citation

Burger DA, Schall R, Jacobs R, Chen D-G. A generalized Bayesian nonlinear mixed-effects regression model for zero-inflated longitudinal count data in tuberculosis trials. Pharmaceutical Statistics. 2019;18:420–432. https://doi.org/10.1002/pst.1933.