Aernoud Fiolet

33 General introduction and thesis outline is low, the prerequisite sample size or follow-up time further increases operational costs. Thus, the provision of return on investment for the sponsor is crucial for embarking large clinical outcome trials. Nature Reviews | Drug Discovery Cost (US$ millions) 75 50 25 0 Phase IP Phase II Phase III Median Mean 3.4 8.6 21.4 Nature Reviews | Drug Discovery Outsourcing Grants/ contracts Personnel Other expenses 22% 21% 21% 37% Figure 5. Trial costs and components. The upper panel shows the distribution of the costs of 726 studies conducted in patients from 2010–2015. Medians and means are indicated with diamonds and lines. Boxes indicate the 25th and 75th percentiles, and whiskers indicate the 10th and 90th percentiles. Phase IP = phase I study involving patients. The lower panel shows the proportion of various components that make up expenses in phase III clinical trials. Data are derived from 273 studies conducted in patients from 2010–2015. Adapted from Martin et al. 120