A new "comprehensive analysis" conducted by the European Medicines Agency (EMA) has found that more than 60% of patients enrolled in pivotal trials submitted in support of drug applications-that is, Phase III clinical trials meant to assess a drug's efficacy and safety in a large patient population-were recruited from outside of the European Economic Area (EEA), calling attention to the difficulties regulators face in policing global clinical trials.
The report, "Clinical trials submitted in marketing authorization applications (MAAs) to EMA" looks at patient recruitment conducted between 2005 and 2011, and was prompted by changes to the EU legislative framework in 2005 that EMA said had succeeded in increasing the "emphasis on the ethical standards required of clinical trials conducted in third countries."
"There is growing concern both among regulators and in public debate about how well these trials are conducted from an ethical and scientific/organizational standpoint, including good clinical practice (GCP) compliance and about the available framework for the supervision of these trials," EMA wrote in the report. As a result, changes were made that now require companies to report in each MAA the location of trials conducted in support of the application, as well as the conduct and ethical standards applied to those trials.
EMA has already provided periodic updates on the information gleaned from those reports, with the first coming in 2009 and the second in 2010. The new report adds the most recent information from 2010 and 2011, EMA explained.
Data Shows Shift to Non-EU/US Countries
The reports include an enormous amount of data, encompassing 677 MAAs, including new applications, line extensions and Type-II variations (changes having a significant impact on the quality, safety or efficacy of a product).
One of the most interesting points of data may simply be how many applications the agency receives each year. EMA said it received 108 applications in 2011, considerably more than the 44 it received in 2005. But the number is also down for the second straight year. In 2009, it received 144 applications, and 117 in 2010.
Other data shows that while trials may be conducted outside of the EEA, that doesn't mean they're being conducted in disreputable areas. In 2011, 31.2% of all clinical trials patients were assessed in EU/EEA/EFTA (European Free Trade Area) regions. Nearly the identical number, 31.5%, we assessed in the US (27.9%) and Canada (3.6%).
The remainder, 37.3% were enrolled in trials conducted elsewhere. The three most prominent regions were Asia and the Middle East (12.8%), the Commonwealth of Independent States (primarily consisting of former Soviet Bloc countries) (7.5%) and Central and South America (13.6%).
Those numbers represent a continual shift toward non-US and non-EU regions over time. In 2005, those regions accounted for just 20.3% of all trials. They're since nearly doubled.
Increase in Trial Sites and Inspections
The number of trials sites, too, had increased markedly since 2005 for non-US/EU regions. In 2005, those regions had just 589 sites (10.5%), while the EU had 1,974 (35.2%) and the US had 3,042 (54.3). In 2011, those regions have mostly gained ground at the expense of the US, with 3,636 sites (28.1%) compared to the US' 4,744 (36.7%) and the EU's 4,548 (35.2%).
All regions, it should be noted, experienced significant amounts of growth in terms of both patients enrolled and trial sites.
EMA also said that it has since considerably stepped up the number of good clinical practice (GCP) inspections at sites around the world. In 2005, it conducted just 10 inspections, with seven of those occurring in the EU/EEA. In 2011, it conducted 64 inspections, 18 of which were in the US and 26 of which were outside the US and EU.
In the last three years, EMA has conducted more inspections of non-EU/US facilities for GCP reasons than it has in all other years going back to 1997 combined.
The full report may be found here.