Fig. 1| Trends in clinical development. a| Probability of launch from start of phases I, II and III for new active substances (defined as a chemical, biological, biotech or radiopharmaceutical substance that has not been previously available for therapeutic use in humans and is destined to be made available as a ‘prescription-only medicine’, to be used for the cure, alleviation, treatment, prevention or in vivo diagnosis of diseases in humans). The probability of transition from phase II to phase III is also shown. Source: CMR R&D Performance Metrics, applying the progression decision methodology (PDM), which assesses the fate of active substances exiting a phase within a specified year range (such as 2015–2017), and assigns a fate as ‘progressed’or ‘terminated’(active substances remaining in-phase are not considered within the PDM). These values can then be used to calculate a probability of success to market. Only new drug projects are included, and the number of projects (n) is> 100 for each time point shown in each phase. b| Trends in new drugs entering development. Source: CMR, change in number of new active substances in early development (preclinical, phase I and phase II) and late development (phase III and submission) pipelines, 2009–2017. c| Late-stage development success rate for new active substances targeting rare versus non-rare indications. Source: CMR R&D Performance Metrics, applying the PDM, between phase success rates (phase III to submission and submission to launch), excluding line extensions; n> 90 for non-rare diseases and n= 11–49 for rare diseases. See Supplementary information for details.