POLICY BRIEF  

04 July 2023 

05

Chiara D’Elia – Stefano Tramacere 

REGULATION (EU) NO 536/2014 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL OF 16 APRIL 2014 ON CLINICAL TRIALS ON MEDICINAL PRODUCTS FOR HUMAN USE, AND REPEALING DIRECTIVE 2001/20/EC

CLINICAL TRIALS REGULATION (CTR)

Background. Regulation (EU) 2014/536 is a legislative act of the European Union (EU) governing clinical trials (CTs) conducted in the EEA (EU, Norway, Iceland, and Liechtenstein). With this regulation, the EU aims to promote the efficiency of CTs, especially in the case of trials conducted in more than one Member State (MS), while stimulating innovation and research and limiting duplication of evaluation and repetition of trials without added value. This approach, among other things, is the basis for the voluntary harmonization procedure already underway among MSs. 

Thus, this regulation was created with the aim to establish a favourable environment to carry out of CTs in Europe. This objective would be reached through the harmonization of the rules and processes for their evaluation and supervision, while guaranteeing the highest standards for the safety of participants and the transparency of information. This last result would be reached thanks to the publication of all information concerning the authorization, conduct and results of each trial conducted in EU. 

To improve the transparency of information on CTs, a dedicated portal for the management of all trials in Europe (Clinical Trials Information System, CTIS) has been developed. CTIS will be crucial for increasing transparency and to enable the strengthening of collaboration, information exchange and decision-making processes between and within MSs. Authorization and supervision of CTs will remain the responsibility of the MSs, while the European Medicine Agency (EMA) will manage the CTIS and the publication of its contents in the public section of the portal. 

Since this target could not be achieved efficiently by each MS individually, a European intervention was deemed more effective. The EU took the initiative to legislate in this specific field by relying on the principle of subsidiarity enshrined in Article 5 of the Treaty. In this way, areas of regulatory autonomy at national level are reduced to a minimum. 

HIGHLIGHTS 

  • Clinical study. Any investigation in relation to humans intended: to discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products; to identify any adverse reactions to one or more medicinal products; or to study the absorption, distribution, metabolism and excretion of one or more medicinal products with the objective of ascertaining the safety and/or efficacy of those medicinal products. 
  • Clinical trial. A clinical study which fulfils any of the following conditions: 
  • the assignment of the subject to a particular therapeutic strategy is decided in advance and does not fall within normal clinical practice of the Member State concerned;  
  • the decision to prescribe the investigational medicinal products is taken together with the decision to include the subject in the clinical study; 
  • diagnostic or monitoring procedures in addition to normal clinical practice are applied to the subjects. 
  • Single authorization. The regulation introduces a single (i.e., harmonized) authorization dossier system for CTs conducted in more than one EU country. This simplifies the authorization process, as the applicant can submit a single application that will be evaluated by all competent authorities involved. 
  • Increased transparency. The regulation promotes transparency in CTs by adopting a single portal, managed by the European Commission, for applying to conduct a CTs, linked to an EU database. This allows patients and researchers to access information on ongoing CTs and the results of completed trials. 
  • Safety standards. The regulation establishes harmonized standards for the protection of patients participating in CTs. 
  • Part I: on the scientific-technical merits quality, non-clinical and clinical. State of knowledge, clinical question, hypothesis to be tested, clinical relevance, objectives, endpoints, safety measures, risk-benefit. 
  • Part II: local ethical and feasibility aspects (patient information, informed consent, insurance, etc.). 
  • Role of Competent Authorities. The regulation clarifies the roles and responsibilities of competent authorities of MS. These must designate a competent authority responsible for evaluating and authorizing clinical trials in their territory. 

POTENTIALLY RELEVANT SCENARIOS 

  • Simplification of permit procedures: to avoid multiple submission of information, provision of a single application file through a single portal. 
  • Harmonization of standards: the regulation applies to all CTs conducted in the EEA.  
  • Increased transparency: establishment of an electronic safety communication database (Art. 40) managed by EMA ex Art. 42 and 43 communications (e.g., suspected adverse reactions/ serious adverse reactions/ unexpected serious adverse reactions). 
  • Improved access to information: within one year after completion, summaries of the CTs results are submitted to the EU database (Annex IV), accompanied by a written summary in a way that is understandable to non-experts. 
  • Harmonized standards of safety and protection of patients: a CTs may only be conducted if (a) the rights, safety and dignity of subjects are protected and take precedence over all other interests (e.g., scientific, and ethical review pursuant to Art. 4) and (b) it is designed to generate reliable and robust data. 
  • Protection of subjects and informed consent: Chapter V provisions to allow CTs. 

RELEVANT INTERPRETATIONS 

EDPB Opinion 3/2019 concerning the Questions and Answers on the interplay between CTR and GDPR has stated that, for data protection purposes, consent is not an appropriate legal basis in research activities where there is a clear imbalance of power between the data subject and the controller. It is acknowledged that in clinical trials such an imbalance may exist depending on the circumstances, for instance, when the data subject is not in a good health condition and there is no available therapeutic treatment outside the clinical trial. Therefore, it is stated in this Opinion that, if consent is still to be relied upon to process personal data in clinical trials, “a particularly thorough assessment” of the circumstances of the clinical trial must first be carried out to determine if consent is appropriate. As this Opinion is limited to the specific context of – some – clinical trials, there is room for a different approach depending on the circumstances and the balance of power between the data subject and the controller in other types of scientific research. Therefore, Opinion 3/2019 does not exclude the possibility for the data controller to rely on explicit consent as a legal basis for processing data from patients (hospitalized or not). Explicit consent as a legal basis can still be relied on in medical research projects where it can be established that no imbalance of power between data subjects and researchers exists and the requirements for explicit consent in GDPR can be met. However, this will require careful assessment on a case-by-case basis. 

CROSS-REFERENCE WITH OTHER POLICY/LAW INITIATIVES 

CTR and GDPR apply simultaneously: CTR states that “Member States shall apply Directive 95/46/EC [GDPR now] to the processing of personal data carried out in Member States pursuant to this Regulation”; GDPR explicitly refers to relevant legislation applicable to clinical trials (recitals 156 and 161).