Planned amendment of the Directive by the EU

Nicola Gökbuget, Kristina Ihrig, Sina Hehn; Department of Medicine II, Hematology/Oncology, Goethe University Hospital, Frankfurt, Germany; from the 8th Informationletter, February 2012.

The Clinical Trials Directive 2001/20/EC which was implemented by the EU in 2001 and taken over into German law and other national European regulations until 2004 had severe negative impact on the independent academic research in Germany. This is mainly due to the fact that henceforth treatment optimisation studies and academic trials had to follow the same regulatory processes as registration trials of the pharmaceutical industry. Ethics committees, regulatory and local surveillance authorities already evinced a maximal stringent interpretation of the regulatory general framework in terms of these trials in Germany but also in other countries. In doing so one disregards the fact that therapeutic optimisation studies do not pose an additional risk for the patients. Contrariwise the obstruction of these trials becomes a sizable risk towards adequate and high-class therapy.
Ever since there have been numerous publications expressing massive criticism about the national and European legislation [1-6]. Because of this the EU commission represented by the Industries and Enterprise Directorate-General and later by the Health and Consumers Directorate-General already called to comment on this issue publicly in 2009.
Given the planned revision of the directive 2001/20/EC a public consultation process was initiated anew in 2011. Already the introduction of the consultation paper indicates that the EU commission is aware of the problems arising from the EU directive in particular the lack of European harmonisation and the inhibition of the independent clinical research. The consultation procedure was aiming to answer questions of how to precisely improve the legal provisions. For example it was dealing with the modalities of submission to the authorities in international trials, the fillings with ethics committees, risk assessment for clinical trials, the differentiation of academic and industry-funded studies, definition of the term ‘investigational medicinal product’, patient insurances, the shared role of the sponsor in international studies and the definition of non-interventional studies.
Representing the German Competence Network for Acute and Chronic Leukemias, the Competence Network for Malignant Lymphoma, the German Society for Hematology/Oncology and the European LeukemiaNet we submitted a statement comprising the following core messages:

  1. importance of therapy-optimization studies for the care of patients with hematologic malignancies
  2. bureaucratic obstacles through a complicated ethic application procedure for multicentric trials in Germany including the absurd expansion for proofs of qualification of investigators and the lack of international harmonization
  3. tight definition of interventional trials and the need for a risk adapted definition of clinical trials
  4. the complex of problems concerning expensive patient insurances which in fact never take over payments
  5. excessive but most of the times useless safety-reports, e.g. SUSARs

A great opportunity for the improvement of regulatory settings lies in the risk-adapted classification of clinical trials. From authority’s perspective, ‘risk’ in this regard means the risk for patient rights and safety as well as data quality. According to this a study having a therapeutic approach that corresponds to the standard treatment and measuring a clearly defined end-point, e.g. survival, exhibits a low risk. Thus the regulatory requirements for such a trial should be limited to an absolute minimum. We prefer the definition of treatment optimisation studies as non-interventional trials. In this case there would be only one approval of an ethics committee at the PI’s location, but no notification to national authorities, no patient insurance and no time-sensitive safety-management. A clear definition for this type of study needs to be worked out.
You can find the complete statement on the ELN homepage ( - Content - International Trials - Basic information). At present it is unclear whether the EU commission will submit the proposed draft law to an additional public consultation. Because of the time-consuming political processes in Brussels and in the EU parliament the implementation is not to be expected within the next three years.


Amendment of CT 2001/20/EC

CT 2001/20/EC, statement, EU consultation