The European Medicines Agency (EMA) has launched the next phase of its strategy to tighten up the supervision of clinical trials conducted in ‘third’ countries by releasing for consultation a reflection paper addressing ethical and Good Clinical Practice (GCP) issues around studies from countries that do not belong to the European Union or the European Economic Area.

The wide-ranging paper, which is open for comments until 30 September 2010, highlights the need for co-operation between international regulatory authorities in this sphere and proposes a series of measures to ensure a robust framework for both the oversight and conduct of clinical trials, regardless of where sites are located or patients recruited.

The Reflection Paper on ethical and GCP aspects of clinical trials conducted in third countries for evaluation in marketing authorisation applications for medicines for human use, submitted to the EMA was drafted by a Working Group on third-country clinical trials set up by the EMA last year.

This group, the agency explains, was asked to develop “practical proposals for tasks and procedures or guidance” addressing the four areas for action outlined in the EMA’s December 2008 strategy paper, Acceptance of clinical trials conducted in third countries for evaluation in Marketing Authorisation Applications[MAAs]:

- Clarifying the practical application of ethical standards for clinical trials, in the context of EMA activities

- Determining the practical steps to be taken during the provision of guidance and advice in the course of drug development
- Determining the practical steps to be taken during the Marketing Authorisation phase

- International co-operation in the regulation, review and inspection of clinical trials, as well as capacity-building in this field.

The December 2008 strategy paper included a three-year action plan encompassing all areas of EMA activity with a bearing on clinical trials.

As the new paper points out, statistics on the distribution of patients recruited for pivotal trials that were included in MAAs filed with the EMA between January 2005 and December 2009 indicate that certain non-EU countries (not including the US, Canada and countries in the European Free Trade Association) contributed around 26% of the total number of patients enrolled.

Specifically, 2.6% of patients were recruited in South Africa, 1.5% in India, 1.3% in Israel, 0.9% in the Philippines, 0.7% apiece in China and Thailand, 1.2% in Australia, 2.6% in Brazil, 2.2% in Argentina, 1.3% in Mexico, 0.7% in Costa Rica, 0.6% in Peru, 2.9% in Russia, 0.8% in Ukraine and 0.5% in Croatia.

The reflection paper covers various aspects of the four action areas mentioned above and provides an overview of regulatory measures recommended in each of these sections.

So in terms of clarifying the application of ethical standards, for example, the Working Group says competent authorities in the EU should refuse to consider clinical trial data where the sponsor has failed to submit a study protocol to an independent ethics committee.

Or, with respect to international co-operation, the EMA will prioritise third countries “based firstly on the numbers of trial subjects recruited there as part of clinical trials submitted to EMA and secondly on a review of the regulatory systems in place for the supervision of clinical trials in those countries”.

The full reflection paper may be downloaded from the European Medicines Agency’s website at As part of the consultation process, the EMA will hold a workshop on 6-7 September 2010 to review and discuss comments.