The extent to which large numbers of available, ethnically diverse and often treatment-naïve patients in emerging markets are driving clinical trials out of Europe is made clear by a new report from the European Medicines Agency.
The geographical analysis of patient recruitment for pivotal trials submitted in marketing-authorisation applications (MAAs) to the EMA from January 2005 to December 2011 found that 61.9% of patients during that period were recruited in third countries outside the European Economic Area (EEA) and Switzerland.
Among these patients, 27.8% came from the ‘rest of the world’ (ROW) region (i.e., Africa, the Middle East/Asia Pacific, Australia/New Zealand, Central/South America, the Commonwealth of Independent States (CIS) and non-EU Eastern Europe) and 34.1% from North America.
Previous data from the EMA on the patient distribution for pivotal trials included in MAAs filed with the agency between January 2005 and December 2009 showed that non-EU countries, excluding the US, Canada and countries of the European Free Trade Association, contributed around 26% of all patients recruited in that five-year period.
Larger Europe
In the latest report, 38.1% of patients in pivotal trials for MAAs submitted to the EMA in 2005-11 were recruited within the European Union, the European Economic Area (EEA – i.e., the EU member states plus Iceland, Liechtenstein and Norway) or the European Free Trade Association (EFTA: Iceland, Liechtenstein, Norway and Switzerland).
Of those, the EU-15/EEA countries accounted for 27.1% of the patient total (the pre-2004 EU-15 countries are Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Portugal, Spain, Sweden and the United Kingdom).
A further 9.2% of patients were recruited in the EU-10 (the 2004 accession countries: Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Malta, Poland, Slovakia and Slovenia), 1.6% in the EU-2 (the 2007 accession countries: Bulgaria and Romania) and 0.3% in Switzerland.
Richest source
Among the ROW countries in which 27.8% of patients were recruited for pivotal trials in MAAs filed during 2005-11, the Middle East/Asia Pacific and Central/South America were the richest source of patients, with 9.4% apiece of the global total.
Within the Middle East/Asia Pacific, India accounted for 1.87% of patients in pivotal trials, the Philippines for 1.25%, Israel for 1.19% and China for 0.9%.
Brazil was the leading contributor in the Central/South America region, with 2.36% of patients, followed by Argentina with 2.29%, Mexico with 1.72% and Peru with 0.7%.
The CIS generated 4.4% of patients in pivotal trials filed with MAAs during 2005-11 (Russia: 3.13%; Ukraine: 1.20%), while Africa accounted for 2.6% (South Africa: 2.08%).
Sharp drop
Year-to-year comparisons show a sharp drop between 2010 and 2011 in the share of patients recruited for pivotal trials in MAAs that went to the EU/EAA/EFTA countries.
They accounted for 41.6% of these patients in 2010 and only 31.2% in 2011. In the same two years, North America’s share of patients declined only slightly from 32.0% to 31.5%.
By contrast, Central/South America contributed 13.6% of the patient total in 2011, up from 6.2% in 2010, while the CIS share rose from 4.1% to 7.5% and the Middle East/Asia Pacific from 12.1% to 12.8% – although Africa’s share of patients fell from 1.9% in 2010 to 1.6% in 2011.
Inspection resources
Information on the geographical location of clinical trials enables the European medicines network to allocate resources for inspections where they are most needed, the EMA noted.
It also helps to promote co-operation with local regulators and capacity-building “to support and strengthen local supervision in countries where clinical trials are being conducted today”.
The number of Good Clinical Practice inspections carried out in third countries by inspectors from the national competent authorities of the EU/EEA member states on behalf of the European Union more than quadrupled between 2006 and 2011, the EMA pointed out.
A total of 357 sites were inspected at the request of the Agency’s Committee for Medicinal Products for Human Use (CHMP) between 1997 and 2011, with most of these inspections taking place since 2007 (the EMA’s GCP inspection policy was implemented in 2006).
The country outside the EU/EEA/EFTA with the highest number of requested inspections in 1997-2011 was the United States (21.6%), followed by India (4.5%), Canada (4.5%), Russia (3.1%), Argentina (2.2%) and China (1.7%).
