A4S: a user-friendly PKPD simulation software for non experts
Massimiliano Germani(2), Francesca Del Bene(2), Maurizio Rocchetti(2), Dave Fairman(1), Balaji M. Agoram(1), & Piet H. van der Graaf(1)
(1)Pfizer Global Research & Development, Sandwich CT13 9NJ, UK and (2)Accelera, Nerviano (Milan), Italy
Objectives: Effective communication of PKPD principles and results in a biomedical research environment remains a significant challenge [1], which can result in lack of buy-in and engagement from scientists outside the modelling and simulation communities. In our view, one of the barriers in this area is a lack of user-friendly tools which allow ‘non experts' to use PKPD models without the need to develop technical skills and expertise in advanced mathematical principles and specialist software. The costs of large number of licenses for commercial software may also prevent large-scale distribution. One attempt to address this issue internally in our research organisation has resulted in the development of the A4S (‘Accelera for Sandwich') software, which is a simple-to-use basic PKPD simulator targeted at biomedical researchers with little PKPD experience.
Methods: A4S was written in the MATLAB programming language and can run as a standalone tool in a standard Windows environment without the need for any additional software.
Results: A4S is entirely menu driven and takes the user in a step-wise manner through a complete PKPD simulation. A4S contains a range of ‘standard' PK and PD models (including all NONMEM standard ADVAN PK models with the option to switch between different TRANS parameterisations), which can all be combined with each other. Some more ‘advanced' models not available in other standard software as far as we are aware were also implemented, based on specific internal needs (for example mixed zero-and first order absorption and receptor kinetics). Most dosing regimen can be implemented for complex trial simulations. In addition, the software allows for stochastic simulations of either or both the PK and PD components of the model to explore parameter uncertainty/variability.
Conclusions: Within half a year of its rollout, A4S is increasingly being used by project scientists to (1)design preclinical PKPD experiments (2)explore PKPD models and (3)dose predictions. In addition, A4S has been used in educational workshops (both internally and externally), allowing participants with little or no prior PKPD experience to work on hands-on exercises with minimal need for software training.
References:
[1]Sheiner, T. PAGE 16 (2007) Abstr 1112 [www.page-meeting.org/?abstract=1112]