The EU Clinical Trials Regulation (Regulation (EU) No 536/2014, the CTR) is now in full effect, and the Clinical Trials Information System (CTIS) is the single, mandatory entry point for clinical-trial applications across the European Union and the European Economic Area. The CTR replaced the earlier Clinical Trials Directive, moving from a country-by-country model to a harmonised one. This article is a neutral explainer of how the system works following the end of the transition period; it is not legal or regulatory advice.
From directive to regulation
The previous framework, the Clinical Trials Directive, was a directive — meaning each EU member state transposed it into national law, producing variation in how trials were authorised and overseen. Sponsors running multinational trials had to submit separately to each country, with differing requirements and timelines. The CTR is a regulation, applying directly and uniformly across member states, and was designed specifically to harmonise the assessment and supervision of clinical trials. For the focused overview, see our explainer on the EU Clinical Trials Regulation.
What CTIS does
CTIS is the IT backbone of the regulation. It provides a single online portal and database through which sponsors submit one application to run a trial in one or several EU/EEA countries, and through which regulators and ethics bodies coordinate their assessment. It also includes a public-facing component that improves transparency about authorised trials.
- Single submission: one dossier for a trial spanning multiple member states.
- Coordinated assessment: a reporting member state leads the scientific assessment shared across the countries concerned.
- Two-part evaluation: a jointly assessed scientific part and a national part covering country-specific and ethical aspects.
- Transparency: a public portal with information on authorised trials.
The coordinated model means sponsors no longer duplicate a full application in every country; instead, a shared assessment is combined with country-specific evaluation.
The transition period has ended
The regulation became applicable in January 2022, but it included a phased transition to give the system and its users time to adapt. During that window, sponsors could in some cases still start trials under the old directive, and existing trials had a defined period to transition to the regulation and into CTIS. That transition has now concluded: CTIS is the mandatory route, and trials that were approved under the old directive were required to be brought under the CTR framework within the transition timeline.
The end of the transition is significant because it means there is now a single regime in operation. New trials are authorised exclusively through CTIS under the CTR, and the legacy directive pathway is closed.
How an application flows
At a high level, a sponsor compiles a single application dossier and submits it through CTIS, indicating the member states in which the trial is to run. A reporting member state coordinates the scientific assessment (Part I), which is shared across the participating countries, while each member state evaluates the national and ethical aspects relevant to its territory (Part II). Defined timelines structure the process, and the outcome is a single decision per member state delivered through the system. Substantial changes and safety reporting during the trial are also managed within the same platform.
This single-platform approach is intended to make multinational trials more predictable and to reduce duplicative administration, while maintaining rigorous scientific and ethical assessment in each country.
Transparency and public access to trial information
A notable feature of the CTR and CTIS is the emphasis on transparency. The system includes a public component through which information about authorised trials is made available, and the regulation sets expectations around the publication of trial information and, in time, results. This responds to long-standing calls to reduce so-called publication bias — the under-reporting of trials whose findings are inconvenient or negative — by making the existence and outcomes of trials more visible. Certain commercially confidential information and personal data are protected, so transparency operates within defined limits rather than as unrestricted disclosure.
For the research community, this public visibility supports independent scrutiny and helps ensure the evidence base reflects the trials that were actually conducted, not only those that reported favourable results. It connects clinical-trials regulation to the broader open-science direction seen elsewhere in research policy.
How it fits with GCP and global standards
The CTR governs authorisation and oversight within the EU, while the conduct of trials continues to follow Good Clinical Practice. The modernised international GCP guideline is described in our explainer on ICH E6(R3) Good Clinical Practice, and the two operate together: the regulation defines how trials are approved and supervised in Europe, and GCP defines the quality and ethical standards for running them.
The transparency dimension also connects to broader open-science expectations, since CTIS publishes information about authorised trials, supporting public visibility of clinical research. For neutral definitions of related terms, see our standards dictionary.
What it means for sponsors and sites
For sponsors, the end of the transition removes the option of the legacy pathway and concentrates all trial activity in one system, which favours organisations that have built familiarity with CTIS and its document and timeline requirements. For sites and investigators, the harmonised model means the ethical and national assessment of a trial in their country proceeds within a coordinated EU process rather than in isolation. Sponsors running trials in several member states benefit most from the single submission, but even single-country trials in the EU now flow through CTIS. As with any large system, users continued to adapt their internal processes — document preparation, role management within the portal, and response to assessment questions — to work efficiently within the platform.
The takeaway
The EU has moved decisively to a single, harmonised system for clinical trials: one regulation applying directly across member states, one mandatory portal in CTIS, and a coordinated assessment that replaces country-by-country duplication. With the transition period over, CTIS is the only route for trial applications in the EU and EEA. Authoritative detail is published by the European Medicines Agency and the European Commission at ema.europa.eu, which sponsors and investigators consult for binding requirements.