PURPOSE: to promote public health and research throughout the European Union (EU) by establishing harmonised rules concerning the authorisation and the conduct of clinical trials.
LEGISLATIVE ACT: Regulation (EU) 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.
CONTENT: the new Regulation replaces Directive 2001/20/CE and applies to all clinical trials conducted in the Union. It relies on the general principle according to which a clinical trial may be conducted only: a) if the rights, safety, dignity and well-being of subjects are protected and prevail over all other interests; and b) if it is designed to generate reliable and robust data.
According to the Regulation, any clinical trial shall be subject to a scientific and ethical review and shall be subject to prior authorisation. The ethical review shall be performed by an ethics committee in accordance with the law of the Member State concerned.
Procedures for authorisation: the procedure to be used should be flexible and efficient, in order to avoid administrative delays for starting a clinical trial, without compromising patient safety or public health.
To obtain an authorisation, the sponsor must submit one application dossier to all the Member States concerned through a single EU portal. The Regulation sets the deadline for authorisation of clinical trials at 60 days. If no decision is taken within this period, the autorisation shall be deemed to have been given (tacit approval). Decisions on requests for substantial changes to clinical trials should be taken within 49 days. In the absence of a decision, the authorisation will be taken as given.
Application dossier for authorisation of a clinical trial: it should contain information on: a) the conduct of the clinical trial, including the scientific context and arrangements taken; b) the sponsor, investigators, potential subjects, subjects, and clinical trial sites; c) the investigational medicinal products and, where necessary, the auxiliary medicinal products, in particular their properties, labelling, manufacturing and control; d) measures to protect subjects; e) justification as to why the clinical trial is a low-intervention clinical trial, in cases where this is claimed by the sponsor.
Vulnerable people: clinical trials involving subjects in emergency situations, minors, incapacitated subjects, pregnant and breastfeeding women and, where appropriate, other identified specific population groups, such as elderly people or people suffering from rare and ultra rare diseases, will be strictly supervised and their evaluation subject to specific expertise.
Protection of participants: the Regulation stipulates that a clinical trial may be conducted only where certain conditions are met. In particular:
- the anticipated benefits to the subjects or to public health justify the foreseeable risks and inconveniences and compliance with this condition is constantly monitored;
- the subjects have been informed and given their informed consent;
- the rights of the subjects to physical and mental integrity, to privacy and to the protection of the data concerning them are safeguarded;
- the clinical trial has been designed to involve as little pain, discomfort, fear and any other foreseeable risk as possible for the subjects;
- the subject has been provided with the contact details of an entity where further information can be received in case of need;
- no undue influence, including that of a financial nature, is exerted on subjects to participate in the clinical trial.
Informed consent: informed consent must be written, dated and signed by the person conducting the interview and the participant, or if he is not able to give his consent, his legally designated representative.
Information given to the subject or his legally designated representative should allow them to understand: i) the nature, objectives, benefits, implications, risks and inconveniences of the clinical trial; ii) the subject's rights and guarantees regarding his or her protection; iii) the conditions under which the clinical trial is to be conducted, including the expected duration of the subject's participation in the clinical trial; iv) the possible treatment alternatives, including the follow-up measures if the participation of the subject in the clinical trial is discontinued.
In addition, the information should be: i) comprehensive and understandable to a layperson; ii) provided in a prior interview with a member of the investigating team who is appropriately qualified according to the law of the Member State concerned; iii) include information about the applicable damage compensation system.
Transparency: in order to allow patients to assess possibilities to participate in a clinical trial, and to allow for effective supervision of a clinical trial by the Member State concerned, the start of the clinical trial, the end of the recruitment of subjects for the clinical trial and the end of the clinical trial should be notified. In accordance with international standards, the results of the clinical trial should be reported within one year from the end of the trial.
The European Medicines Agency shall set up and maintain an electronic database for the reporting provided for in the clinical trial framework.
Supervision, Union inspections and controls: where a Member State concerned has justified grounds for considering that the requirements set out in this Regulation are no longer met, it may: a) revoke the authorisation of a clinical trial; b) suspend a clinical trial; c) require the sponsor to modify any aspect of the clinical trial. Qualifed inspectors shall be designated by the Membe States to supervise compliance with this Regulation.
The Commission should be able to control whether Member States correctly supervise compliance with this Regulation. Moreover, the Commission should be able to control whether regulatory systems of third countries ensure compliance with the specific provisions of this Regulation and Directive 2001/83/EC concerning clinical trials conducted in third countries.
Union database: in order to streamline and facilitate the flow of information between sponsors and Member States as well as between Member States, the Agency should, in collaboration with Member States and the Commission, set up and maintain an EU database, accessed through an EU portal. In order to ensure a sufficient level of transparency in the clinical trials, the EU database should contain all relevant information as regards the clinical trial submitted through the EU portal.
ENTRY INTO FORCE: 16.06.2014. The Regulation shall apply no earlier than 28.05.2016.
DELEGATED ACTS: the Commission may adopt delegated acts in order to supplement or amend non-essential aspects of the Regulation. The power to adopt such acts shall be conferred on the Commission for a period of five years from the date of the implementation of the Regulation. The European Parliament or the Council may object to a delegated act within a period of two months from the date of notification (this period can be extended for two months). If the European Parliament or the Council make objections, the delegated act will not enter into force.