Medicinal products for human use
Clinical trials - Directive 2001/20/EC
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" (the "GCP Directive") .
Directive 2001/20 EC will be repealed on the day of entry into application of the new Clinical Trials Regulation. It will however still apply three years from that day to:
- Clinical trials applications submitted before the entry into application (no earlier than 28 May 2016);
- Clinical trials applications submitted within one year after the entry into application if the sponsor opted for old system.
The Commission has issued guidance documents in order to ensure a uniform application of the legislation on clinical trials in Europe. The guidelines specify in particular:
- The information 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.
All guidelines for the application of Clinical Trials Directive can be found here.
The relevant guidelines and recommendations are now being revised and updated to be in line with the changes and requirements of the Clinical Trials Regulation.
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 in EudraLex - Volume 10.
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 web page.
EudraCT also contains information on all trials performed anywhere in the world if the trial:
- is part of an agreed paediatric investigation plan (PIP), or;
- is sponsored by a marketing-authorisation holder and involves the paediatric use of a medicine that has a European Union (EU) marketing authorisation. This requirement is set out in Article 46 of the Paediatric Regulation .
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 three "mother guidelines" (Guideline 2008/C168/02, Guideline 2009/C28/01, Guideline 2012/C302/03), setting out the principles, responsibilities, and procedural aspects. The "mother guidelines" are further concretised by way of a number of very detailed "daughter guidelines":
- Guideline 2008/C168/02 on the data fields from the European clinical trials database (EudraCT) that may be included in the European database on Medicinal Products (July 2008).
- List of fields contained in the "EudraCT" clinical trials database to be made public, in accordance with Article 57(2) of Regulation (EC) No 726/2004 and its implementing guideline 2008/C168/02 (February 2009).
- Guideline 2009/C28/01 on the information concerning paediatric clinical trials to be entered into the EU Database on Clinical Trials (EudraCT) and on the information to be made public by the European Medicines Agency (EMEA), in accordance with Article 41 of Regulation (EC) No 1901/2006 (February 2009).
- List of fields to be made public from EudraCT for Paediatric Clinical Trials in accordance with Article 41 of Regulation (EC) No 1901/2006 and its implementing guideline 2009/C28/01 (February 2009).
- Guidance on posting and publication of result-related information on clinical trials in relation to the implementation of Article 57(2) of Regulation (EC) No 726/2004 and Article 41(2) of Regulation (EC) No 1901/2006 (October 2012).
- Technical guidance on the format of the data fields of result-related information on clinical trials submitted in accordance with Article 57(2) of Regulation (EC) No 726/2004 and Article 41(2) of Regulation (EC) No 1901/2006 (278 KB) (January 2013).
As of 21 July 2014, the clinical trial results posted by sponsors in the EudraCT line with the Guideline 2012/C302/03 will become available to the public. This date corresponds to the finalisation of the programming of the database as referred to in a European Commission guideline , in application of the current clinical trials Directive 2001/20/EC and the Paediatric Regulation .
What this means for clinical trial sponsors
Results for any trials registered in EudraCT will be posted in this database. This will apply:
- For any clinical trials that ended on or after 21 July 2014, sponsors will have to post results within six (for paediatric clinical trials) or twelve months (for non paediatric clinical trials) following the end of the trial.
- For trials that ended before 21 July 2014, the guideline sets the specific timeframe for the results submission.
What this means for public access to information on clinical trial results
- A subset of the data included in EudraCT is made available to the public in the European Union Clinical Trials Register, clinicaltrialsregister.eu. A typical set of summary results provides information on the objectives of a given study, explains how it was designed and gives its main results and conclusions. A number of summary results can already be viewed. Only the result related information on Phase I clinical trials on adults is not made public.
- In addition, information on paediatric studies that ended before the Paediatric Regulation came into force in 2007, which used to be accessible through the EMA website, is now available through the European Union Clinical Trials Register. This improvement allows a greater and richer approach to the search and greater public access to clinical trial related information.
For all additional information, please click here.
The Clinical Trials Directive sets 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" 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:
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
Mail to: email@example.com
- United Kingdom
If 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" ).