Bayesian P-spline estimation in hierarchical models specified by systems of affine differential equations

Ordinary differential equations (ODEs) are widely used to model physical, chemical and biological processes. Current methods for parameter estimation can be computationally intensive and/or not suitable for inference and prediction. Frequentist approaches based on ODE-penalized smoothing techniques have recently solved part of these drawbacks. A full Bayesian approach based on ODE-penalized B-splines is proposed to jointly estimate ODE parameters and state functions from affine systems of differential equations. Simulations inspired by pharmacokinetic studies show that the proposed method provides comparable results to methods based on explicit solution of the ODEs and outperforms the frequentist ODE-penalized smoothing approach. The basic model is extended to a hierarchical one in order to study cases where several subjects are involved. This Bayesian hierarchical approach is illustrated on real data for the study of perfusion ratio after a femoral artery occlusion. Model selection is feasible through the analysis of the posterior distributions of the ODE adhesion parameters and is illustrated on a real pharmacokinetic dataset.