The scientific basis of pharmacology is based on the relationship between drug concentration and effect1. Clinical trials typically take a more empirical approach and study the dose-effect relationship. Dose and concentration may both be described as measures of drug exposure. There is no clearly accepted definition of exposure but it commonly refers either to the average dose or to the area under the concentration time curve (AUC). Both these approaches lead to loss of information because the time course of concentration in relation to effect is removed. Many drugs display schedule dependence i.e. the effect depends on the time course of concentration. This has been commonly observed in trials of cancer chemotherapy yet many still advocate AUC for trying to understand the exposure response relationship for these drugs. Clinical trial simulation offers a mechanism for describing how scientific knowledge relates to clinical outcome and can be used as a tool to determine what can be learned from different design choices2.