January 10, 2013 | By Márcio Barra
(Note: this article on the new European clinical trial regulation will consist of two posts, one today, and one tomorrow or sunday. Please keep an eye out and enjoy this article. Also, please share if you enjoy it!)
Originally published in April 2001, Directive 2001/20/EC introduced the standards for conducting clinical trials in the EU Member States (hereby referred as MS) (1), building upon the concepts brought forth by the Council Directive 65/65/EEC of January 26th 1965, which, among others, made mandatory for a marketing authorization of a medicinal product to be accompanied by a dossier containing data of the results of clinical trials conducted (2). It came into effect into 2004, after an adaptation period allowing for each MS to adopt the necessary provisions, and it shaped the EU clinical trial operations with a series of innovations and requirements, such as:
- Rules for conducting a trial
- Created the concept of Ethic Committee (EC), special national bodies that evaluate a clinical trial’s compliance with ethical standards
- A time frame of 60 days for both the National Competent Authority (NCA) and EC to evaluate a clinical trial application, thus addressing time differences between different countries (3)
- In multicenter trials conducted in multiple MS, all MS must give their permission
- Rules for clinical trials on minors and other special populations
- Established a database for clinical trials in Europe, EudraCT, launched in 2004 (1).
In short, since its 2004 enactment, Directive 2001/20/EC, and its accompanying piece, Directive 2005/28/EC (4) (regarding good clinical practices when conducting trials), shaped the current EU clinical trial landscape.
The Directive 2001/20/EC however, from the two public consultations executed by the EC, one from October 9, 2009 to January 8, 2010 (5) and the second from February 9, 2011 to May 13, 2011 (5), is not held in high regard by European stakeholders. From the feedback provided by patient organizations, the pharmaceutical industry, non-commercial research stakeholders and all the MS (6), it’s clear that there is still a long way to go. Directive 2001/20/EC attempted to bring to the EU a standard clinical trial submission and authorization procedure to all MS, but it was not fully successful, mostly because of its directive status – a piece of EU regulation where its provisions must be transposed by each MS into their national law. (7)
These, as pointed out in the consultations (5), led each MS to adopt different interpretations of the Directive. In a way, there are 27 different implementations of the Directive and 27 different sets of rules governing GCP, with key differences between MS on how they handle reimbursements, substantial modifications to a clinical trial, ethic committee constitution, deadlines, and other topics (3) (8).
Another hurdle occurs when a sponsor wishes to conduct a trial in more than one EU country, an increasingly more common situation, as, more than ever, clinical trials are a multinational affair (3). In those cases, as stated by the Directive (1), a sponsor has to obtain authorization from all the MS where he wishes to conduct the trial. Then, each country conducts its separate assessment of the application. With each MS having two distinct evaluating bodies (the NCA and one or more Ethic Committees), who often require MS specific submission material, it’s not uncommon for different MS to reach different conclusions, delaying the whole process (7) (9). Directive 2001/20/EC does not take into account the new clinical trials reality, and as such burdens clinical trials.
Even low risk trials, usually with already marketed drugs which pose few risks for the patients, fall into difficulties, as they are subject to the same regulatory scrutiny as higher impact trials(9).
End of part 1