Commission proposes new rules to boost clinical trials in Europe

Clinical trials are investigations in humans intended to discover or verify the effects of one or more investigational medicinal products ("IMPs").

Requirements for the conduct of clinical trials in the EU are provided for in " 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" (" the Clinical Trials Directive ").

The Clinical Trials Directive is concretised further by " Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products" (Good Clinical Practice - "the GCP Directive ").

Clinical trials performed in the European Union are required to be conducted in accordance with the Clinical Trials Directive. If the clinical trials are conducted outside the EU, but submitted in an application for marketing authorisation in the EU, they have to follow the principles which are equivalent to the provisions of the Clinical Trials Directive (cf. Annex I, point 8 of the "Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use" - " the Community Code for medicinal products ").

Guidelines

There are a number of guidelines further specifying various aspects of clinical trials, and in particular:

• The inforation to be submitted to the competent authorities and to the ethics committees
• The requirements on safety monitoring and the reporting of adverse reactions
• The requirements regarding Good Clinical Practice, including the documentation, of the clinical trials
• The specific requirements regarding the products and the clinical trials
• The inspections of competent authorities and the applicable procedures

These guidelines have been published by various bodies:

• By the European Commission: In this case, they are published in Volume 10 of "EudraLex - The rules governing medicinal products in the European Union"
• By the European Medicines Agency ("EMA") These guidelines concern in particular:
  • Inspection procedures and guidance for GCP inspections conducted in the context of the Centralised Procedure
  • Requirements relating to the quality, safety and efficacyof products, as well as specific types of products. Volume 3 of EudraLex
• Moreover, the Heads of Medicines Agencies have established a Clinical Trials Facilitation Group ("CTFG") (in which the Commission and EMA are observers), in order to discuss ongoing technical issues.

Clinical trial application

The Clinical Trials Directive harmonises the rules in the EU for the approval of a clinical trial conducted in a Member State. As regards national competent authorities, the details are set out in the 'Commission Detailed guidance on the request to the competent authorities for authorisation of a clinical trial on a medicinal product for human use, the notification of substantial amendments and the declaration of the end of the trial (CT-1)' published inEudraLex Volume 10.

EudraCT

A European database - EudraCT - contains all ongoing or completed clinical trials falling within the scope of Directive 2001/20/EC, i.e. with at least one investigator site in the EU (incl. the European Economic Area) and commencing after implementation of Directive 2001/20/EC by the Member States. This database gives the competent authorities of the Member States, the EMA and the Commission the necessary information to communicate on clinical trials and to maintain oversight of clinical trials and IMP development. This provides for enhanced protection of clinical trial subjects and patients receiving IMPs. More information, including a user manual for EudraCT is available on the EudraCT Supporting Documentation web page.
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<>Paediatric clinical trials that form part of a Paediatric Investigation Plan (PIP) but are conducted in third countries will also be included in the near future (paediatric clinical trials with sites in the EU/EEA are already included).

Transparency of information related to clinical trials

Union legislation provides that certain information contained in EudraCT is to be made accessible to the public. This public accessibility concerns clinical trials with paediatric as well as non-paediatric participants. It englobes protocol-related information and result-related information. And it covers both negative and positive results.

To implement the legislation further, the Commission has issued a set of guidelines, which are accessible via chapter V of EudraLex, Volume 10.

These guidelines consist of two "mother guidelines" (Guideline 2008/C168/02 and Guideline 2009/C28/01), setting out the principles, responsibilities, and procedural aspects. The "mother guidelines" are further concretised by way of a number of very detailed "daughter guidelines".

With regard to protocol-related information, this information is public underclinicaltrialsregister.eu, which is part of the public database EudraPharm.

With regard to result-related information, this information is presently not contained in EudraCT at all. Therefore, prior to making anything public, work has to focus on the format and procedure to submit this information by the sponsor in the first place. Programming has to be adapted to this. More information is available here.

For all additional information, reference is made to the applicable guidelines in chapter V ofEudraLex Volume 10.

Safety reporting

The Clinical Trials Directive introduces rules on safety reporting in the context of a clinical trial. Further details are set out in 'the Commission Detailed guidance on the collection, verification and presentation of adverse event/reaction reports arising from clinical trials on medicinal products for human use (‘CT-3’)' published in EudraLex Volume 10. Regarding suspected unexpected serious adverse reactions (SUSARs), this guidance provides inter alia the rules for reporting directly to the national competent authority. In order to obtain the national address for the direct reporting, click on the relevant Member State:

Austria (mail or by fax to: Bundesamt für Sicherheit im Gesundheitswesen (BASG), Österreichische Agentur für Gesundheit und Ernährungssicherheit (AGES) PharmMed, Institut Pharmakovigilanz, Schnirchgasse 9, A-1030 Wien, Österreich, Fax: +43 (0) 50555-36207),Denmark, Germany, Greece, Ireland, Italy (susar-ita@aifa.gov.it), Netherlands, Portugal,Sweden, United Kingdom.