The Council of the European Union recently approved the new Clinical Trials Regulation with the stated purpose of making the EU a more attractive place to conduct clinical research. Many will remember that in 2001 the Clinical Trials Directive (CTD) was supposed to do the same thing, but the CTD is now widely considered to have made the situation worse. As a directive, the CTD’s provisions became effective only when they were transposed into national law in each of then 15 EU member states (MSs) and the 3 European Economic Area countries that follow the EU for clinical trial legislation. A few years after implementation an Impact on Clinical Research of European Legislation survey reported that—despite the harmonisation goals of the CTD—“the differences between the countries have become even larger rather than smaller.”1 Now the number of MSs has reached 28 (welcome, Croatia!), complexity has multiplied, and applications for clinical trials have decreased by 25%.2
The good news is that the new regulation is a regulation rather than a directive and thus has the force of law in each MS. The less good news is that the only real harmonisation introduced is the regulatory approval process, and even that change is somewhat limited. The new process seems broadly similar to the Voluntary Harmonisation Procedure that has been available in the EU for several years and about which I have heard positive reports. Application to all MSs in which the clinical trial is planned will be made via 1 submission portal, and a single response will be received with the opinions of each MS. Each MS will still assess the application separately though.
An interesting aspect of the regulatory process in the new regulation is the reinforcement of the idea of tacit approval, that is, if a response to a clinical trial application is not received in 60 days, the clinical trial may commence in all the MSs to which the application was made. Although this provision was available in the CTD and was practiced by at least 1 member state that had a practice of not confirming approval in writing, I know tacit approval is a concept with which many pharmaceutical companies are not comfortable in Europe.
The new regulation is a behemoth! A whopping 85 clauses follow the initial “whereas” (vs 19 in the CTD), and then there are 99 articles (vs 24 in the CTD). A lot of this verbiage is welcome delineation and clarification of important issues such as protection of vulnerable individuals, responsibilities of co-sponsors, identification of low-intervention clinical trials, and clinical trials conducted in emergency situations. A lot of it will also look familiar to sponsors accustomed to ICH-GCP and other international standards for performing clinical trials.
I’ll follow-up with posts on new reporting challenges posed by the regulation and issues for medical writers.
I am interested in hearing from you. Will the Clinical Trials Regulation solve the problems of the CTD? Will it make Europe more attractive for clinical trials? Will it make our jobs easier or more difficult?
1Project Final Report. Available at http://www.efgcp.be/downloads/icrel_docs/Final_report_ICREL.pdf.
2Council of the European Union. Council adopts new rules on clinical trials. Available at http://www.consilium.europa.eu/uedocs/cms_data/docs/pressdata/en/lsa/142181.pdf
