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

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.