Bayesian analysis of population PK/PD models: general concepts and software

Abstract

Markov chain Monte Carlo (MCMC) techniques have revolutionized the field of Bayesian statistics by enabling posterior inference for arbitrarily complex models. The now widely used WinBUGS software has, over the years, made the methodology accessible to a great many applied scientists, in all fields of research. Despite this, serious application of MCMC methods within the field of population PK/PD has been comparatively limited. We appreciate that for many applied pharmacokineticists the prospect of conducting a Bayesian analysis will require numerous alien concepts to be taken on board and it may be difficult to justify investing the time and effort required in order to understand them (especially since the approach is so computer-intensive). For this reason we provide here a thorough (but often informal) discussion of all aspects of Bayesian inference as they apply specifically to population PK/PD. We also acknowledge that while the WinBUGS software is general purpose, model specification for some types of problem, population PK/PD being a prime example, can be very difficult, to the extent that a specialized interface for describing the problem at hand is often a practical necessity. In the latter part of this paper we describe such an interface, namely PKBugs. A principal aim of the paper is to offer sufficient technical background, in an easy to follow format, that the reader may develop both the confidence and know-how to make appropriate use of the PKBugs/WinBUGS framework (or similar software) for their own data analysis needs, should they choose to adopt a Bayesian approach.