a Registered clinical trials (x10 3 ) Registered clinical trials (x10 3 ) 0 50 100 150 200 250 300 350 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Africa Latin America Oceania North America Europe Asia United States Other high income: OECD High income: non-OECD Upper-middle income Lower-middle income Low income b Registered clinical trials (%) 0 40 30 20 10 50 60 70 80 90 100 2005 2006 2007 2008 2009 2010 2011 2012 c 0 50 100 150 200 250 300 350 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 d Registered clinical trials (%) 0 40 30 20 10 50 60 70 80 90 100 2005 2006 2007 2008 2009 2010 2011 2012 Organizations that conduct clinical trials are increasingly using global networks to reduce costs and accelerate recruitment. Because the migration of clinical trials from countries such as the United States to other countries where the health-care infrastructure is less developed has public health, economic, social and ethical implications, we explored a large repository of open-access trial registry data to understand changes in the global distribution of clinical trials. We examined data on 205,455 clinical trials from 15 global primary trial registries, conducted in 163 countries from 1999 to 2012 (Supplementary information S1, S2 (boxes)). The first 6 years (1999–2004) represented just 8% of all registered trials, and numbers increased sharply in 2005 after the introduction of registration requirements by the International Committee of Medical Journal Editors (ICJME) (FIG. 1a). The 30,964 clinical trials registered globally during 2012 represented a 66% increase from the 18,692 trials registered during 2005. Clinical trials were classified by geographical region. Over the 2005–2012 period overall, 127,314 (67%) of the 189,213 registered trials were conducted in the United States, Canada or Europe (see Table 2 in Supplementary information S2 (box)). The United States was the single largest country conducting clinical trials, with 58,980 trials (30%). The absolute increase was greatest for the Asian region (489%) and the Latin American/Caribbean region (112%); the smallest increase occurred in the North American region (9%) (FIG. 1b). Clinical trials were also classified by the economic development status of the countries involved. Over the 2005–2012 period overall, 77% of trials were conducted in the group of 24 high-income OECD (Organisation for Economic Co-operation and Development) countries, including the United States (FIG. 1c; see Table 2 in Supplementary information S2 (box)). From 2005, absolute growth was highest among lower-middle-income (594%) and low-income (247%) countries (FIG. 1d). Meanwhile, high-income non-OECD and high-income OECD countries excluding the United States had increases of 36% and 59%, respectively. There was an 11% increase in the absolute number of trials conducted in the United States, but the proportion of trials globally decreased from 35% in 2005 to 24% in 2012. The proportion of registered trials globally increased in low-income (2% to 5%) and lower-middle-income (4% to 16%) countries (P < 0.0001). The highest average clinical trial densities over the 2005–2012 period were in North America, Europe and Oceania, as well as in high-income OECD and non-OECD countries. The 48 low-income countries averaged 0.3 trials per 10 6 people, or one clinical trial for every 3 million people. Denmark had the highest average trial density (107 trials per 10 6 people), and other high-density countries included Estonia, the Netherlands, Israel and Finland (see Table 5 in Supplementary information S2 (box)). The largest average annual growth rate from 2005 to 2012 occurred in Asian (30%) and Latin American/Caribbean (12%) regions; other geographic regions had growth rates that were lower than the global average (8%; see Table 2 in Supplementary information S2 (box)). The largest average annual growth occurred in lower-middle-income (33%) and low-income (21%) regions. Emerging economies among low-middle-income countries (such as Iran, China and Egypt) had the largest country-specific growth; other countries with high growth rates included South Korea, Japan, India, Brazil and Turkey (see Table 6 in Supplementary information S2 (box)). The United States had an average annual growth rate of 2%. Overall, the data show that the number of registered clinical trials has increased TRIAL WATCH Global migration of clinical trials Figure 1 | Global migration of clinical trials. The total annual number of registered clinical trials between 1999 and 2012 (part a) and percentage distribution between 2005 and 2012 (part b) by United Nations geographic region. The total number of trials is 205,455, and includes Africa (3,983), Latin America (8,117), Oceania (10,418), North America (75,128), Europe (66,396) and Asia (41,413). The total annual number of registered clinical trials between 1999 and 2012 (part c) and percentage distribution between 2005 and 2012 (part d) with countries classified by the World Bank economic development category. Data for United States and other high-income OECD countries are shown separately. The total number of trials is 213,331, and includes the United States (69,007), other high-income OECD countries (94,844), high-income non-OECD countries (10,201), upper-middle- income countries (12,621), lower-middle-income countries (19,648) and low-income countries (7,010). For details of the data and analysis, see Supplementary information S1 (box). NEWS & ANALYSIS BIOBUSINESS BRIEFS 166 | MARCH 2014 | VOLUME 13 www.nature.com/reviews/drugdisc © 2014 Macmillan Publishers Limited. All rights reserved