Abstract

The simulation of therapeutic models and clinical trial simulation have recently attracted attention as emerging techniques for developing new active molecules and the exploration of possible clinical trial results. Such approaches have benefited from fundamental progress in the development of 'in silico' models, as well as progress in nonlinear mixed-effect pharmacokinetic-pharmacodynamic models. Mixing the two approaches allows simulation of 'virtual' patients, who receive virtual treatments or placebo. These have various uses, such as proof of concept, decision analysis or experimental design optimisation. Also, the effect of departures from protocol on clinical trial results can easily be evaluated by the use of simulation. This technique is now implemented by the pharmaceutical industry for optimising phase II and III experimental designs when a good biomarker or a clinical outcome model is available, but the use of an in silico therapeutic model as a proof of concept is only just beginning. In order to see such methodologies used more widely in drug development, multidisciplinary efforts need to be initiated, new modelling and simulation tools developed, and sound modelling and simulation practice documents need to be adopted. A reduction in the number of failed clinical development projects, the number of negative phase II and III clinical trials, or in just their cost and duration, are among the expected benefits of modelling and simulation in clinical drug development.