Location of clinical trials shifts away from EU, finds EMA report
More than 60% of patients recruited outside the region
Nearly 62% of the patients in clinical trials submitted in marketing-authorisation applications (MAAs) to the European Medicines Agency (EMA) between January 2005 and December 2011 were recruited outside the European Economic Area (EEA) and Switzerland, according to analysis by EMA.
The report, Clinical trials submitted in marketing-authorisation applications to the European Medicines Agency, provides an overview of the distribution of the numbers of patients, investigator sites and pivotal clinical trials included in MAAs submitted to EMA, as well as the number and location of sites that were inspected.
More than 34% of patients were enrolled in North America, and nearly 28% in Africa, the Middle East, Asia, the Pacific, Australia, New Zealand, Central or South America, and the Commonwealth of Independent States (CIS) or non-European Union (EU) Eastern Europe.
In excess of 9% of patients (9.4%) were recruited in the Middle East, Asia or the Pacific, and another 9.4% in Central or South America.
EMA 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.
Middle East/Asia/Pacific saw an increase from 2% in 2005 to 12.8% in 2011
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.
The number of patients submitted in MAAs to the European Medicines Agency in Middle East/Asia/Pacific saw an increase from 2% in 2005 to 12.8% in 2011; while in CIS there was an increase from 0.8% in 2005 to 7.5% in 2011.
In contrast, the EU/EEA/ European Free Trade Association (EFTA) saw a drop from 37% in 2005 to 31.2% 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% to 19.4%. The contribution of the countries that became Member States of the EU in 2004 and 2007 increased from 4.7% in 2005 to 11.7% in 2011.
North America also saw a decline – from 42.8% in 2005 to 31.5% in 2011.
The number of GCP inspections in third countries carried out by the inspectors of the EU/EEA Member States on behalf of the EU 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.
The US has the highest number of requested inspections
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 sites.
The US has the highest number of requested inspections (21.6%), followed by India (4.5%), Canada (4.5%), Russia (3.1%), Argentina (2.2%) and China (1.7%).
The top three countries where bioequivalence trials for generic applications were inspected are 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, EMA published a reflection paper on ethical and GCP aspects of clinical trials conducted outside the EU/EEA and submitted in MAAs to the EU regulatory authorities.
The paper placed a specific emphasis on international cooperation and capacity-building initiatives for a common approach to oversight of trials. It also clarified and determined the practical steps by which EU regulators will gain assurance that ethical and GCP standards are applied to clinical trials for human medicines, during both the development and the marketing-authorisation-application phase.