ICRIN explains how the proposed European Clinical Trial Regulation could lead to a significant increase in research activity throughout the European Union. This article was published in the Irish Pharma Chem Yearbook 2013/14.
Clinical trials represent an essential component of evidence based medical research. Prior to 2001 each European member state had its own national clinical trials regulations and approval systems (e.g. Clinical Trials Act 1987 and 1990 in Ireland). This increased the complexity of multi-national European clinical research primarily due to differing requirements and approval mechanisms between countries. In an attempt to standardise and harmonise clinical trial approvals amongst member states the European Commission introduced the first European Clinical Trials Directive EC 2001/20 (CTD).
The CTD 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” has ensured a high level of patient safety. However divergence in its transposition into national law and interpretation has “led to an unfavourable regulatory framework for clinical research in Europe” 1 contributing to a 25% decline in the annual number of clinical trial applications across the EU with a corresponding doubling of administrative costs.2 The absence of a consistent pan-european regulatory framework is one of the key reasons for this. The decline is of great concern to those who directly benefit from or work in clinical trials namely patients clinicians academia and the pharmaceutical industry.
In July 2012 the European Commission (EC) adopted a proposal for a Clinical Trials Regulation. The proposed Regulation aims to resolve a number of issues identified with the current legislation on clinical trials and once passed will replace the current Clinical Trials Directive in regulating the clinical trials of medicinal products in patients across Europe.
The Irish Clinical Research Infrastructure Network (ICRIN) with the Irish Medicines Board (IMB) and Health Information & Quality Authority (HIQA) held a stakeholder seminar in March 2013 in the Mansion House Dublin to inform and initiate discussions on how Ireland could effectively implement the European Commission draft regulation on clinical trials. The seminar focused on identifying the changes required nationally to ensure Ireland can comply with all the legal requirements of the proposed Regulation without significant disruption to clinical trial activity during the changeover period.
Clinical research accounts for greater than €20 billion/annum of investment in the EU. According to John Dalli European Commissioner for Health and Consumer Policy the proposed new regulation could save up to €800 million/annum in regulatory costs whilst simultaneously boosting research activity throughout the European Union. “Patients in Europe should have access to the most innovative clinical research” he commented.
The new Regulation as proposed by the Commission in consultation with various stakeholders such as patients academia and industry representatives will apply directly to all 27 Member States and effect harmonisation of the legislation for conducting clinical trials across Europe. It should result in simplifying the rules for healthcare research across Europe and therefore encourage faster development of new medicines as well as review and improvement of authorised medicines.
The proposed Regulation aims to increase the number of trials conducted in the EU by directly addressing the key criticisms of the EC 2001/20 (CTD). The resulting new legislation will apply the same rules equally in all 27 countries for carrying out clinical trials across the EU and will be transposed without interpretation into national legalisation.
While the Commission’s legislative proposal appears to be a big step forward it is not expected to be enacted until 2016. The Regulation will replace directive EC 2001/20 (CTD). but must first be jointly agreed by both the European Parliament and European Council. The proposed legislation aims to streamline the process of applying and gaining authorisation to conduct clinical trials in Europe and simultaneously assuring data quality and protecting patient safety3.
The Regulation sets clear objectives and timelines for the assessment and decision on clinical trials by Member States while respecting international guidelines such as Good Clinical Practice (ICH-GCP) and the World Medical Association’s ethical standard the “Declaration of Helsinki”.
Under the new Regulation:
1. A “single portal” system will allow applicants seeking to conduct trials in multiple geographies to submit a single application. It will ensure a swift and comprehensive assessment with a single decision.
2. Simplified reporting procedures will reduce the burden of submitting largely identical information separately to various bodies.
3. The Commission will introduce mechanisms to ensure the rules are enforced consistently in each member state.
4. There will be a greater focus on patient safety and protection through the consideration of varying levels of risk to subjects participating in clinical trials by the introduction of the concept of a low and high risk trial.
5. Introduction of proportionate approaches to trial management will be introduced for example; frequency of on-site monitoring and independent monitoring of data and patient safety to dynamically adapt risk management plans for clinical trials.
6. Introduction of increased transparency will be introduced into clinical research. From May 2011 clinical trials approved in the EU have been published in an official register and the move towards increasing transparency of clinical research continues under the new regulation. Patients will be able to find clinical trials that they may be interested in participating in and will be able to easily assess clinical trial results both positive and negative thereby reducing publication bias.
There is uniform support for a revision of the current Directive for drug clinical trials. However some challenges remain with respect to compliance with the short timelines indicated and the alignment of the ethics and competent authority systems in order to produce a single national opinion.
By streamlining authorisation and reporting processes the new regulation will decrease the level of onerous and often duplicated paperwork whilst facilitating timely start-up of multinational clinical trials. With this new regulation the commission hopes to re-establish the EU a key location of choice for the conduct of clinical studies with a direct focus on the patient.
1. European Commission Fostering EU’s attractiveness in clinical research: Commission proposes to revamp rules on trials with medicines 2012 visit: http://europa.eu
2. European Commission Proposal for a Clinical Trials Regulation – Questions and Answers 2012 visit: http://europa.eu
This article was co-authored by Siobhan Gaynor Fionnuala Gibbons and Susan Lennon members of the Irish Clinical Research Infrastructure Network (ICRIN) team in Molecular Medicine Ireland.