Clinical trials

General Information

Revision of the Clinical trials Directive

Major developments

General Information  

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/ECpdf 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 Directivepdf ").

On 16 April 2014 the new Regulation No 536/2014 of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC was adopted, and published in the Official Journal on 27 May 2014. It entered into force on 16 June 2014 but will apply no earlier than 28 May 2016.

Until then the Clinical Trials Directive pdfwill still apply. In addition, the transitory provisions of the Regulation offer the sponsors the possibility to choose between requirements of the Directive or the Regulation for 1 year from the entry into application of the regulation.[AC1] 

The Clinical Trials Directive is concretised further by " Commission Directive 2005/28/ECpdf 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 Directivepdf ").

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/ECpdf 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 productspdf ").

Guidelines

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

These guidelines have been published by various bodies:

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 in EudraLex 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 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".

With regard to protocol-related information, this information is public under clinicaltrialsregister.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, the necessary guidelines had to be adopted and published. These are published in EudraLex, Volume 10. Programming of the relevant databases is currently ongoing. More information is available here.

For all additional information, reference is made to the applicable guidelines in chapter V of EudraLex 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.

 Revision of the Clinical trials Directive

Adoption of the new Regulation on clinical trials

On 16 April 2014 the new Regulation No 536/2014 of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC was adopted, and published in the Official Journal on 27 May 2014. It entered into force on 16 June 2014 but will apply no earlier than 28 May 2016.

Until then the Directive 2001/20/EC pdfof 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 pdf") will still apply.

In addition, the transitory provisions of the Regulation offer the sponsors the possibility to choose between requirements of the Directive or the Regulation for 1 year from the entry into application of the regulation.

Adoption of the proposal for a "Clinical Trials Regulation"

On 17 July 2012, the Commission adopted a "Proposal for a Regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/ECpdf(767 KB) Choose translations of the previous link български (bg) čeština (cs) dansk (da) Deutsch (de) eesti keel (et) ελληνικά (el) español (es) français (fr) Gaeilge (ga) italiano (it) latviešu valoda (lv) lietuvių kalba (lt) magyar (hu) Malti (mt) Nederlands (nl) polski (pl) português (pt) română (ro) slovenčina (sk) slovenščina (sl) suomi (fi) svenska (sv) " (hereinafter "Clinical Trials Regulation") .

The adoption was announced in a press releasepdf(97 KB) Choose translations of the previous link български (bg) čeština (cs) dansk (da) Deutsch (de) eesti keel (et) ελληνικά (el) español (es) français (fr) italiano (it) magyar (hu) Malti (mt) Nederlands (nl) polski (pl) português (pt) română (ro) slovenčina (sk) slovenščina (sl) svenska (sv) , supported by a 'questions and answerspdf(64 KB) Choose translations of the previous link Deutsch (de) français (fr) ' document.

The Commission proposal was accompanied by an impact assessment report (Volume Ipdf(673 KB)Volume IIpdf(502 KB)) and a summarypdf(65 KB) Choose translations of the previous link български (bg) čeština (cs) dansk (da) Deutsch (de) eesti keel (et) ελληνικά (el) español (es) français (fr) Gaeilge (ga) italiano (it) latviešu valoda (lv) lietuvių kalba (lt) magyar (hu) Malti (mt) Nederlands (nl) polski (pl) português (pt) română (ro) slovenčina (sk) slovenščina (sl) suomi (fi) svenska (sv) thereof.

In addition, a 'citizen summary' pdf(128 KB) Choose translations of the previous link български (bg) čeština (cs) dansk (da) Deutsch (de) eesti keel (et) ελληνικά (el) español (es) français (fr) italiano (it) latviešu valoda (lv) lietuvių kalba (lt) magyar (hu) Malti (mt) Nederlands (nl) polski (pl) português (pt) română (ro) slovenčina (sk) slovenščina (sl) suomi (fi) svenska (sv) was published.

The proposalwas submitted to the European Parliament and the Council who engaged in ordinary legislative procedure. You may find an overview of this procedure here. To follow the proposal in the different steps of the procedure, please consult the "legislative observatory" of the European Parliament  or PreLex, the EU-database on interinstitutional procedures.

Preparation of the Commission proposal

In its Communication of 10 December 2008 to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions on “Safe, Innovative and Accessible Medicines: a Renewed Vision for the Pharmaceutical Sector”, the Commission announced that an assessment would be made of the application of the Clinical Trials Directive.

This assessment would consider, in particular, various options for improving the functioning of the Clinical Trials Directive with a view to making legislative proposals, if appropriate, while taking the global dimension of clinical trials into account.

In 2009, a public consultation document along this line was published herepdf(134 KB). The responses have been published here. A summary document of the responses is available herepdf(61 KB).

A 'roadmap' of the Commission impact assessment, setting out the main structure and the next steps, was made available here.

On 9 February 2011, a public consultation on a concept paper on the revision of the 'Clinical Trials Directive' 2001/20/ECpdf(94 KB) has been launched. The concept paper presented:
- a 'preliminary appraisal' of which option appeared to be the most suitable one to address some of the key concerns of the Clinical Trials Directive, on the basis of the current state of the impact assessment; and
- the main figures used to evaluate the impacts of the different policy options.

The responses to this public consultation are published here. A summary of the responses is herepdf(95 KB).

Useful contact points

For further information, please find below the relevant contact points:

Other useful links

Clinical Trials - Major developments