CLINICAL PHARMACOLOGY & THERAPEUTICS | VOLUME 0 NUMBER 00 | Month 2019 1 STATE OF THE ART Development Times and Approval Success Rates for Drugs to Treat Infectious Diseases Joseph A. DiMasi 1, *, Maria I. Florez 1 , Stella Stergiopoulos 1 , Yaritza Peña 1 , Zachary Smith 1 , Michael Wilkinson 1 and Kenneth A. Getz 1 We gathered data from three pipeline databases and other public sources on development stage and clinical trial metrics for 1,914 investigational drugs, biologics, and vaccines and 2,769 clinical trials intended to treat a wide variety of infectious diseases. We included new molecular entities (NMEs), new formulations, and new combinations. Clinical trial times decreased from 2000–2008 to 2009–2017, varied by disease class, and were longer for trials with more subjects or more sites. Clinical approval success rates were higher for this set of diseases than those in the published literature for drugs across all therapeutic categories. NMEs to treat HIV had a success rate (16.0%) that was similar to those for drugs in general, whereas NME success rates for influenza and pneumonia were much higher (48.1% and 50.5%, respectively). Drug development in general is lengthy, risky, and costly. 1 Additionally, development metrics tend to vary substantially by a number of factors, most notably therapeutic class. 2–6 Thus, the optimal application of benchmark metrics for particular groupings of investigational drugs for planning or other purposes is best achieved when enough data and analysis are available for the subset of drugs under consideration, rather than making use of analysis for drugs as a whole. The need for the development of drugs for neglected diseases, which has been inhibited by a limited ability to pay for and provide access to marketed drugs, has been argued and documented by many. 7–9 As a re- sult, new funding models and incentives have been explored. 10,11 One recent study has quantified the amount of funding required to pursue the development of a pipeline portfolio of neglected disease drugs in active development on August 31, 2017, finding that there was a sub- stantial current shortfall in what would be needed to complete the proj- ects. 12 To ascertain funding requirements, the authors estimated phase development times and transition rates. However, their analysis was applied to a snapshot of 538 drug candidates in active development at a particular point in time and relied on expert opinions in addition to development data. This study differs in a number of ways. We do not take a snapshot approach for a portfolio of drugs at a particular point in time but, rather, we started with drugs that have entered clinical devel- opment over a lengthy period and followed their outcomes over time. Our focus was also not on neglected diseases only, but primarily on a wide array of infectious diseases (many of which, though, are neglected diseases). Specifically, we examined metrics for drugs targeted at the portfolio of diseases and conditions that a major philanthropic funder (The Bill and Melinda Gates Foundation) is interested in targeting. BACKGROUND For this study, we examined the drug development pipelines for a wide array of, primarily neglected, infectious diseases that the Gates Foundation identified as areas of interest and a focus of funding. We aggregated the data on these diseases and conditions into seven major and one miscellaneous disease categories for this portfolio based on their prevalence in the dataset. The full list of indications examined is provided in the online Supplementary Data File (Table S1 ). Epidemiological and cost burden data are available for these categories from information gathered by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). HIV The WHO reports that, in 2017, roughly 940,000 people died from HIV-related causes globally. There were ~ 36.9 million peo- ple living with HIV at the end of 2017, and roughly 1.8 million of those cases were in newly infected individuals. 13 According to a study by the Global Burden of Disease Health Financing Collaborator Network, in 2015, governments spent US $29.8 bil- lion (61% of the total money spent) fighting HIV and AIDS. 14 Pneumonia and influenza Pneumonia is the single largest infectious cause of death in chil- dren worldwide, accounting for 16% (or 920,136) of deaths of under 5-year-old children in 2015. 15 The global cost of antibiotic treatment for all children with pneumonia for maternal, newborn, and child survival is estimated at around US $109 million per year. This figure includes the costs of antibiotics and diagnostics for pneumonia management. 15 Malaria In 2016, nearly half of the world’s population was at risk of ma- laria. According to the latest World Malaria Report, released in November 2017, there were 216 million cases of malaria in 2016, and the estimated number of malaria deaths stood at 445,000. 16 More than 70% of all malaria deaths occur in children under Received June 10, 2019; accepted August 22, 2019. doi:10.1002/cpt.1627 1 Tufts Center for the Study of Drug Development, Tufts University, Boston, Massachusetts, USA. *Correspondence: Joseph A. DiMasi ( joseph.dimasi@ tufts.edu)