Aernoud Fiolet

32 Chapter 1 or international drug authorities. These requirements are strongly focused on reducing the risk of false-positive results and are driven by the principal goal of ensuring the safety of participants. This makes these phases of research costly. The estimated costs for the complete route of drug research until market authorisation can reach from 800 million up to 1.5 billion US dollars in the current era. 119 (Figure 4) N NME cost (US$ billions) 2.0 1.5 1.0 0 0.5 2010 1990 1970 1950 a y = 1E–113e 0.1335x R 2 = 0.98 Log (NME cost) 8.0 6.0 4.0 0 2.0 1970 1950 b y = 0.1335x–260 R 2 = 0.98 Nature Reviews | Drug Discovery 2010 1990 Log (NME cost) 8.0 6.0 4.0 0 2.0 2010 1990 1970 1950 b y = 0.1335x–260 R 2 = 0.98 Figure 4. The exponential costs of new drugs. Panel A shows a plot of twelve independent estimates of the cost of a new molecular entity (NME) spanning 48 years, reaching 1.5 billion US dollars. Panel B shows the same data plotted on a logarithmic scale. The exponent in the line equation in Panel A and the gradient of the line in Panel B show that the cost per NME has grown at an annual compound rate of 13.35% since the late 1950s. Adapted from Munos. 119 The cost of research includes the development of the compound, production, and exploratory preclinical research (phase I and II clinical research) with limited participants. Large clinical outcome trials (phase III clinical research) are more costly endeavours. Median costs of conducting such trials are estimated at 21 million US dollars per drug, but can reach over 75 million US dollars. 120 (Figure 5) When the incidence of the primary outcomemeasure in the final efficacy evaluation