Clinical trials in human medicines
The European Medicines Agency relies on the results of clinical trials carried out by pharmaceutical companies to reach its opinions on the authorisation of medicines. Although the authorisation of clinical trials occurs at Member State level, the Agency plays a key role in ensuring that the standards of good clinical practice (GCP) are applied across the European Economic Area (EEA) in cooperation with the Member States. It also manages a database of clinical trials carried out in the European Union.
Clinical trials are studies that are intended to discover or verify the effects of one or more investigational medicines. The regulation of clinical trials aims to ensure that the rights, safety and well-being of trial subjects are protected and the results of clinical trials are credible.
Regardless of where they are conducted, all clinical trials included in applications for marketing authorisation for human medicines in the European Economic Area must have been carried out in accordance with the requirements set out in Annex 1 of Directive 2001/83/EC. This means that:
- clinical trials conducted in the EEA have to comply with European Union (EU) clinical-trial legislation (Directive 2001/20/EC);
- clinical trials conducted outside the EEA have to comply with ethical principles equivalent to those set out in the EEA, including adhering to international good clinical practice and the Declaration of Helsinki.
In the EEA, approximately 4,000 clinical trials are authorised each year. This equals approximately 8,000 clinical-trial applications, with each trial involving two Member States on average. Approximately 61% of clinical trials are sponsored by the pharmaceutical industry and 39% by non-commercial sponsors, mainly academia.
Role of the Agency
Clinical-trial data is included in clinical-study reports that form a large part of the application dossiers submitted by pharmaceutical companies applying for a marketing authorisation via the Agency.
The Agency's Committee for Medicinal Products for Human Use (CHMP) is responsible for conducting the assessment of a human medicine for which an EU-wide marketing authorisation is sought. As part of its scientific evaluation work, the CHMP reviews the clinical-trial data included in the application.
Assessments are based on purely scientific criteria and determine whether or not the medicines concerned meet the necessary quality, safety and efficacy requirements in accordance with EU legislation, particularly Directive 2001/83/EC.
Good clinical practice
The Agency plays a central role in ensuring application of good clinical practice (GCP). GCP is the international ethical and scientific quality standard for designing, recording and reporting clinical trials that involve the participation of human subjects.
The Agency works in cooperation with GCP inspectors from medicines regulatory authorities ('national competent authorities') in EEA Member States on the harmonisation and coordination of GCP-related activity at an EEA level.
The Agency does not have a role in the approval of clinical-trial applications in the EEA. The approval of clinical-trial applications is the responsibility of the national competent authorities.
EudraCT database and the EU Clinical Trials Register
The Agency is responsible for the development, maintenance and coordination of the EudraCT database. This is a database used by national competent authorities to enter clinical-trial data from clinical trial sponsors and paediatric-investigation-plan (PIP) addressees.
A subset of this data is made available through the European Union Clinical Trials Register, which the Agency manages on behalf of EU Member States and forms part of EudraPharm, the EU database of medicines.
Users are able to view:
- the description of phase-II to phase-IV adult clinical trials where the investigator sites are in the EEA;
- the description of any clinical trials in children with investigator sites in the EU and any trials that form part of a PIP including those where the investigator sites are outside the EU.
The content and level of detail of these summary results is set out in a European Commission guideline and in its technical guidance. 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. As of 21 July 2014, it is mandatory for sponsors to post clinical trial results in the EudraCT database.
As of October 2016, the Agency publishes clinical reports submitted by pharmaceutical companies to support their regulatory applications for human medicines under the centralised procedure. For more information, see clinical data publication.
Clinical trials conducted in countries outside the EU
Clinical trials conducted outside the EU but submitted in an application for marketing authorisation in the EU have to follow the principles which are equivalent to the provisions of the Directive 2001/20/EC.
In April 2012, the Agency published the final version of this paper:
- Reflection paper on ethical and GCP aspects of clinical trials of medicinal products for human use conducted outside of the EU / EEA and submitted in marketing-authorisation applications to the EU regulatory authorities .
This paper aims to strengthen existing processes to provide assurance that clinical trials meet the required ethical and GCP standards, no matter where in the world they have been conducted.
The number of clinical trials and clinical-trial subjects outside Western Europe and North America has been increasing for a number of years. More information is available in this document:
- Clinical trials submitted in marketing-authorisation applications to the European Medicines Agency: Overview of patient recruitment and the geographical location of investigator sites
New Clinical Trials Regulation
On 16 April 2014 the European Commission adopted the new Clinical Trial Regulation (EU No 536/2014), repealing Directive 2001/20/EC. The Regulation entered into force on 16 June 2014 but will apply no earlier than 28 May 2016. For more information, see Clinical Trials Regulation.
Clinical Trials Facilitation Group
- acts as forum for discussion to agree on common principles and processes to be applied throughout the European medicines regulatory network;
- promotes harmonisation of clinical-trial-assessment decisions and administrative processes by national competent authorities;
- operates the voluntary harmonisation procedure for assessment of clinical-trial applications involving several Member States.
The Group is composed of representatives from the clinical-trial departments of the national competent authorities.