According to an analysis carried out by the European Medicines Agency (EMA), almost 62 per cent of the patients in pivotal trials submitted in marketing authorisation applications (MAAs) to the agency between January 2005 and December 2011 were recruited outside of the European Economic Area (EEA) and Switzerland. The analysis provides an overview of the distribution of the numbers of patients, investigator sites and pivotal clinical trials included in MAAs submitted to the Agency, as well as the number and location of sites that were inspected.

More than 34 per cent of patients were enrolled in North America, while almost 28 per cent were recruited in Africa, the Middle East, Asia, the Pacific, Australia, New Zealand, Central or South America, the Commonwealth of Independent States (CIS) or non-European Union (EU) Eastern Europe. Of note, 9.4 per cent of patients were recruited in the Middle East, Asia or the Pacific and another 9.4 per cent in Central or South America.

The EMA closely monitors the data that applicants must include in their MAAs on the location of studies and the ethical standards applied in respect of clinical trials conducted outside the EU. Applicants have had to include this information since the revisions to the European pharmaceutical legislation in 2005, which reinforced the emphasis on ethical and good-clinical-practice (GCP) standards.

The information on the geographical location of clinical trials allows the European medicines network to allocate resources for inspections where they are most needed, and to promote cooperation with local regulators and capacity-building activities to support and strengthen local supervision in countries where clinical trials are being conducted today.

Major trends in the number of patients submitted in MAAs to the European Medicines Agency during the observation period were: Middle East / Asia / Pacific: an increase from 2.0 per cent in 2005 to 12.8 per cent in 2011; CIS: an increase from 0.8 per cent in 2005 to 7.5 per cent in 2011.

In the EU/ EEA/ European Free Trade Association (EFTA), there was a decrease from 37.0 per cent in 2005 to 31.2 per cent in 2011. Within this region, the contribution of the 15 countries that were members of the EU before May 2004 plus Norway, Iceland and Liechtenstein fell from 32.1 per cent to 19.4 per cent over the observation period. The contribution of the countries that became Member States of the EU in 2004 and 2007 increased from 4.7 per cent in 2005 to 11.7 per cent in 2011. In North America, there was a decrease from 42.8 per cent in 2005 to 31.5 per cent in 2011.

The number of GCP inspections in third countries carried out by the inspectors of the national competent authorities of the EU / EEA Member States on behalf of the EU has increased by more than four times between 2006 and 2011. Both routine and triggered inspections have increased over the years. Routine inspections are requested as part of the ongoing surveillance of the quality of studies received in MAAs, while triggered inspections are requested when the assessors identify specific concerns with the report and data on a trial which need a specific investigation by inspection.

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 inspections taking place since 2007. The pivotal trials submitted between 2005 and 2011 involved 70,291 investigator sites.

The country outside of the EU/ EEA/ EFTA area with the highest number of requested inspections was the United States (21.6 per cent), followed by India (4.5 per cent), Canada (4.5 per cent), Russia (3.1 per cent), Argentina (2.2 per cent) and China (1.7 per cent).

The top three countries where bioequivalence trials for generic applications were inspected were India, Italy and Canada.

All clinical trials included in an MAA submitted in the EU have to comply with the EU’s legal requirements and with international GCP and ethical standards wherever in the world they have been carried out. It is the applicant’s responsibility to ensure compliance with these standards.

In 2012, the EMA published a reflection paper on ethical and GCP aspects of clinical trials conducted outside of the EU/ EEA and submitted in MAAs to the EU regulatory authorities. The paper put forward concrete steps for international cooperation in the regulation of clinical trials, with a specific emphasis on international cooperation and capacity-building initiatives for a common approach to oversight of trials. It also clarifies and determines the practical steps by which EU regulators will gain assurance that ethical and GCP standards are applied to clinical trials for human medicines, both during the development and during the marketing-authorisation-application phase.