Has the European Clinical Trials Directive been a success?BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1862 (Published 09 April 2010) Cite this as: BMJ 2010;340:c1862
- L J Frewer, chair of food safety and consumer behaviour1,
- D Coles, research associate2,
- K Champion, clinical trials director3,
- J Demotes-Mainard, project coordinator, ECRIN4,
- N Goetbuget, head of study centre and project leader 5,
- K Ihrig, scientific coordinator5,
- I Klingmann, chairman, EFCGP6,
- C Kubiak, executive manager, ECRIN 4,
- S A Lejeune, European Union programme officer, EORTC7,
- F McDonald, executive officer, EBMT3,
- J Apperley, chair of haematology8
- 1University of Wageningen, 6701 BH Wageningen, Netherlands
- 2University of Central Lancashire, Preston PR1 2TQ
- 3European Group for Blood and Marrow Transplantation, 08036 Barcelona, Spain
- 4INSERM, 75013 Paris, France
- 5Information Center of European Leukemia Net, Goethe University, 60590 Frankfurt, Germany
- 6Pharmaplex bvba, 1970 Wezembeek-Oppem, Belgium
- 7EORTC, Brussels 1200, Belgium
- 8Department of Haematology, Imperial College, London W12 0NN
The laudable aims of the European Clinical Trials Directive (EU 2001/20/EC) were to improve the safety and efficiency of both commercial and investigator driven clinical trials and to provide the basis for improved European competitiveness. Unfortunately, even before the directive was finalised, concerns were voiced about potential adverse effects on studies designed to test and implement scientific discoveries in clinical practice (translational research) in Europe.1 2 Today, five years after implementation, evidence shows that the directive has had a negative effect on translational research.
The directive was designed to optimise patient safety, increase the numbers of patients entered into clinical trials, improve the efficiency of trial implementation, ensure best practice in ethical review and regulatory procedures, and harmonise these procedures across Europe. In fact, the implementation of the directive by individual EU member states has caused legislative differences between the different nations and obstacles to the conduct of clinical trials.3 Although practice has improved in some areas of Europe,4 in general the regulatory requirements are highly demanding and expensive, irrespective of the level of risk to which the patient will be subjected by participating in the study; trial implementation is now slower; and investigator (rather than drug company) driven studies are decreasing in number and complexity. All these effects are compounded in the context of multinational studies, where it has been impossible to comply with each nation’s ethical and regulatory requirements that are theoretically similar but different in practice.5 6 7 8 9 10 11
The EU has responded to the concerns by funding initiatives to identify the impact of the Clinical Trials Directive and others to promote international collaboration; to date, nine European organisations have participated in four such collaboratives (table⇓). All have identified problems with the interpretation of the directive in member states and will feed into the review of the directive due in October 2010.
In addition, the scientific standing committee of the European Science Foundation has recently completed a “Forward Look” on investigator driven clinical trials.12 The European Science Foundation has made 25 recommendations to improve the conduct of translational research in Europe that include not only revision of the regulatory issues but also the need for training and education and adequate funding for approved studies. The four collaboratives (table), whose focus was restricted to the regulatory issues, together with the European Organisation for Research and Treatment of Cancer (EORTC), have identified concerns that overlap with each other and mirror many of the recommendations of the European Science Foundation. These five organisations have now shared their experiences and have identified possible solutions to the most important obstacles to clinical trials in Europe (box).
Possible solutions to obstacles to clinical trials in Europe
Require only one clinical trials authorisation (CTA) for all multinational clinical trials, irrespective of the numbers of participating nations, either by development of a single CTA application across Europe or mutual recognition of authorisations by competent authorities
Simplify and harmonise the procedures for clinical trial approval (for example, use just one set of forms) and safety reporting (EudraVigilance and reporting rules)
Better define and harmonise the roles and review processes of ethics committees (achieve the so called single opinion) and competent authorities
Adopt a risk based approach—adapt the regulatory requirements to consider the risk associated with the trial with regard to safety reporting (for example, limited safety reporting for commercially approved drugs), data monitoring, insurance, application dossiers, substantial amendments
Allow co-sponsorship in the case of multinational trials, with the aim of facilitating collaboration between research groups
Better define terms and concepts (for example, investigational medicinal product (IMP), interventional study, substantial amendment)
Increase public financial support for investigator driven clinical trials
Harmonise insurance requirements—for example, uniform costs per country, minimum and maximum indemnity payments, total duration of coverage, and time to permit claims
The directive will undergo formal review in 2010, and this will provide an opportunity to develop practical and concrete proposals for consideration within the EU. From 2009 to 2010 CLINT (facilitation of international CLINical Trials in stem cell transplantation), ECRIN (European Clinical Research Infrastructure Network), EORTC, and ICREL (Impact on Clinical Research of European Legislation) each hosted one or more workshops designed to provide input into a concept for modification that will promote clinical research in Europe. This enterprise culminated in a final meeting in March 2010, organised by EFCGP (European Forum for Good Clinical Practice) at which the results of each were summarised, discussed, and prioritised with the aim of designing a proposal for consideration by the commission. The crucial factor in the success of this initiative was to engage all the key stakeholders (commercial and non-commercial sponsors, investigators from all areas of medicine, ethics committee members, competent authorities, funding bodies, and patients). The voice of academics was unusually silent during the development of the directive—now is the time to be heard.
Cite this as: BMJ 2010;340:c1862
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: (1) No financial support for the submitted work from anyone other than their employer; (2) No financial relationships with commercial entities that might have an interest in the submitted work; (3) No spouses, partners, or children with relationships with commercial entities that might have an interest in the submitted work; (4) No non-financial interests that may be relevant to the submitted work.
Provenance and peer review: Not commissioned; externally peer reviewed.