A Conference on

Impact on Clinical Research of European Legislation – ICREL: Results & Discussion

2 December 2008, Diamant Centre, Brussels, Belgium

ICREL is a one-year project financed by the European 7th Framework Programme. Under EFGCP’s coordination, ECRIN, EORTC, as well as the Hospital Clínic of Barcelona and the Medical University of Vienna collaborate in this project. Its aim is to measure and analyse the direct and indirect impact of the Clinical Trials Directive 2001/20/EC and related legislations in the EU on all categories of clinical research and on the different stakeholders: commercial and non-commercial sponsors, ethics committees and competent authorities. This initiative fits with the need to adapt the current legislation and will help determine the most relevant pathways for improvement.

More details about the project: www.efgcp.be/ICREL.

Conference Rationale
The European Union Clinical Trials Directive 2001/20/EC (EU CTD) was released with the objective of harmonising the regulatory systems, of improving the protection of study participants, of optimising the use of safety information, of ensuring the quality of studies and the credibility of data. As a consequence, the Directive 2001/20/EC ⁱ was adopted on April 4th, 2001 and to be implemented by all Member States on May 1, 2004 (in fact, transposition into national legislation entered into force between 2004 and 2006 in the various EU member states). Rather surprisingly, and due to the role assigned to the European Union (facilitating circulation of products and services, whereas health and ethics remain areas of national policy), this Directive was prepared by DG Enterprise and Industry, and its scope is restricted to clinical trials on medicinal products, an area of major challenge for the industry. This new EU legislation increased the responsibility of clinical trial sponsors and decreased that of the investigators; it led to shared responsibilities between ethics committees and competent authorities, and improved the patients’ protection ⁱⁱ. A single sponsor in the EU, covered by liability insurance for study-related harm to study participants, has now to submit a clinical trial authorisation application to the national competent authority, and in parallel a request for a single favourable opinion to Ethics Committee(s). With the EU CTD, an EMEA-located database for study identification (EudraCT) was implemented and a section for clinical trials added to the EudraVigilance database.

Through harmonisation of the regulatory framework of clinical research, the EU CTD was expected to foster multinational collaboration, to make European clinical science more competitive and the European Union more attractive for industry-sponsored clinical trials. However, many stakeholders now have the feeling that, due to application of the same rules to all types of drug trials and divergent transposition of the Directive’s principles into pre-existing national legislations, the Directive partly missed its facilitation and harmonisation targets. In addition, the Directive is considered to impose unnecessary administrative burden and costs which is especially problematic for investigator-initiated clinical research. Therefore industry and academic stakeholders frequently claim (not exactly for the same reasons) for changes in the EU regulatory framework for clinical research ⁱⁱⁱ .

The European Commission (DG Enterprise and Industry) and the European Medicines Agency organised a conference in October 2007 to discuss the possible changes to be brought to the Directive. Simultaneously, the DG Research funded, through the health priority of the FP7 cooperation programme, the ICREL (Impact on Clinical Research of European Legislation) project to provide metrics and thus objective arguments for the need to adapt the current legislation with the objective of making clinical research more competitive in the European Union whilst providing fair and equivalent protection to participants in every category of clinical research. ECRIN, EORTC, the Hospital Clínic I of Barcelona and the Ethics Committee of the Medical University of Vienna are collaborating in this project coordinated by EFGCP (www.efgcp.be/ICREL).

ICREL collects:

information on positive and negative impact factors on clinical trials with medicinal products and on other types of clinical research

figures on the impact of the legislation on the clinical research activity of big Pharma Industry-, SME-, academia-sponsored trials

data on the resource, cost and effectiveness implication of the CTD implementation for all stakeholders

comparison of the success of national CTD implementation

consolidated conclusions on the findings amongst the stakeholders

As data from individual countries, based on different methodologies, suggest that the impact of the CTD may vary from one country to another ^iv, the collection of data throughout the European Union, with the same methodology, will certainly help further describe and interpret this impact.

ICREL’s methodology includes the collection, comparison and interpretation of figures from all EU member states on all types of clinical trials on medicinal products sponsored by pharmaceutical companies, biotechnology, SMEs, and academic institutions, on other categories of clinical research, as well as on the impact on ethics committees, competent authorities, clinical research infrastructure, and on the workload, cost and funding of clinical trials. It compares the situation before (2003) and after (2007) the implementation of Directive 2001/20/EC. Detailed data were obtained through a series of questionnaires targeting the different stakeholders: commercial and non-commercial sponsors, ethics committees and competent authorities.

This work has been presented and discussed during the Conference held in Brussels on December 2nd, 2008. The resulting discussion and interpretation is expected to help improving Europe’s attractiveness and competitiveness for clinical research by delivering the facts for proposing pathways for improvement of the clinical trial environment in the EU, allowing to better balance a high level of patient protection, optimal use of safety information, high quality and credibility of data, with acceptable cost and workload for investigators, sponsors, ethics committees and competent authorities, for both national and multinational studies in the EU.

The Conference programme can be downloaded by clicking at the top of the page.

For further information, please contact us at icrel@efgcp.be.

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i Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. OJEC 1.5.2001, L 121/34-44
ii Editorial: Who is afraid of the European clinical trials Directive. Lancet 361:2167, 2003.
iii Druml C, Singer EA, Wolzt M. Report of the 1st meeting of the "Vienna Initiative to Save European Academic Research (VISEAR)" Wien Klin Wochenschr. 2006 Apr;118(5-6):Suppl 1-12
iv Berendt L, Hakanson C, Friis Bach K, Dalhoff K et al. Effect of European Clinical Trial Directive on academic drug trials in Denmark: retrospective study of applications to the Danish Medicines Agency, 1993-2006. BMJ, 336:33-35, 2008.
Agenzia Italiana del Farmaco. Bulletin on Clinical trials of drugs in Italy, 2007. http://oss-sper-clin.agenziafarmaco.it
Courcier S, Sibenaler C, Couderc M, Trinquet F, Plétan Y, Lassalle C,  La France est un pays attractif pour la recherche clinique : enquête 2006 du LEEM. Thérapie, 61:407-418, 2006.