Clinical trial approval in Europe involves several stakeholders whose respective roles can sometimes be difficult to distinguish. The EMA, national competent authorities and ethics committees all contribute to the clinical trial regulatory framework, but they do not operate at the same level or assess the same aspects.
Since Regulation (EU) No 536/2014 became applicable and the Clinical Trials Information System (CTIS) was introduced, the clinical trial approval procedure has become more harmonised at European level. However, the decision to authorise a trial remains the responsibility of each Member State concerned.
In France, the ANSM and the French ethics committees, known as Comités de protection des personnes (CPP), are involved in the assessment, while the EMA is notably responsible for the operation of CTIS. So, in practical terms, who does what?
Clinical Trial Approval: A European Framework, National Decisions
Regulation (EU) No 536/2014 establishes a fundamental principle: a clinical trial must undergo scientific and ethical assessment before it can be conducted.
In particular, the process must ensure that participants’ rights, safety, dignity and well-being are protected and that the study is designed to generate reliable and robust data.
Since 31 January 2023, new applications for authorisation of medicinal product clinical trials in the European Union and European Economic Area have been submitted through CTIS, which provides a single entry point for sponsors. However, centralising the application does not mean centralising the decision: each Member State concerned remains responsible for the decision in its own territory.
What Is the Role of the EMA?
In the clinical trial approval process, this is probably the point that causes the most confusion. The European Medicines Agency (EMA) plays a major role in the European medicines regulatory system, but it does not itself authorise clinical trials conducted in the Member States.
Under the Clinical Trials Regulation, the EMA is notably responsible for maintaining CTIS. This platform enables sponsors to submit applications, communicate with authorities during the assessment, manage several regulatory stages of the trial and contribute to the transparency of published information.
For clinical trial approval, CTIS is therefore the common European infrastructure. It does not replace national competent authorities or ethics committees.
Why Is the Application Divided into Part I and Part II?
To understand the roles of the different stakeholders in clinical trial approval, it is useful to look at the assessment structure established by the European regulation. The application is divided into two main parts.
Part I: Common Scientific Aspects
In the clinical trial approval process, Part I covers aspects of the trial that can be assessed in a coordinated manner by the Member States concerned. It includes, in particular, the protocol, data relating to the investigational medicinal product, and information used to assess the scientific rationale and the benefit-risk balance.
When a trial involves several countries, a Reporting Member State (RMS) coordinates this assessment. The other Member States concerned participate in the process and may provide comments.
Part II: National and Ethical Aspects
For clinical trial approval, Part II is assessed separately in each Member State concerned. It covers, in particular, recruitment arrangements, participant information and informed consent, any compensation for participants, investigator suitability, site suitability and certain aspects relating to data protection.
This structure enables coordinated European assessment of common elements while preserving the review of ethical and national aspects specific to each country.
In France, What Is the Role of the ANSM?
In France, the ANSM is the competent authority involved in clinical trial approval for trials involving medicinal products. It is involved in the scientific and regulatory assessment of the application and in the French organisation of the Part I assessment.
Its assessment notably covers the elements required to evaluate participant safety and the scientific robustness of the trial: the protocol, available data on the investigational medicinal product, the benefit-risk balance and the conditions of use of the product.
In a multinational trial, France may act as the Reporting Member State and coordinate the Part I assessment, or participate in the assessment as a Member State concerned. The ANSM’s role does not end with the initial authorisation: it is also involved in trial oversight and in the assessment of certain safety information or modifications during the course of the trial.
What Is the Role of the CPPs in France?
“Ethics committees” have different structures and names across European countries. In France, this role is performed by the Comités de protection des personnes (CPP), the French ethics committees responsible for protecting research participants.
For medicinal product clinical trials falling under the European regulation, the CPPs are particularly involved in assessing ethical aspects and Part II. They review, among other things, how participants will be informed and recruited, informed consent, participation arrangements, and the suitability of the individuals and sites involved in the research.
However, the boundary between “scientific” and “ethical” assessment is not completely rigid. The French system provides for coordination between the ANSM and the CPPs so that relevant ethical considerations can also be taken into account in the Part I assessment. The system therefore cannot simply be reduced to “Part I = ANSM” and “Part II = CPP”.
One CTIS Application, but a Decision in Each Country
Consider a clinical trial planned in France, Spain and Germany. The sponsor submits a single application through CTIS. A Reporting Member State coordinates the assessment of the common Part I. In parallel, each of the three countries assesses the Part II elements that apply to its territory.
At the end of the process, each Member State issues its own decision for its territory. The same multinational trial may therefore be authorised in some Member States but not in another if the conditions laid down in the regulation are not met in that country.
A More Coordinated European Procedure Without Removing National Responsibilities
Regulation (EU) No 536/2014 has profoundly changed clinical trial approval in Europe. The system can be summarised as follows:
CTIS centralises → Member States assess → competent authorities and ethics committees collaborate → each Member State decides.
The EMA provides and maintains the common European environment through CTIS. The Reporting Member State coordinates the common Part I assessment. In France, the ANSM performs the functions of the competent authority, while the CPPs contribute to the ethical assessment in accordance with the national system.
This allocation of responsibilities serves a dual objective: to harmonise and simplify multinational trials in Europe while maintaining rigorous scientific assessment and appropriate protection of participants in each country concerned.
