Examples
Worked examples
- Is an instance
A sponsor plans a Phase III oncology trial across Germany, France, and Poland and submits one CTIS application; Germany (as Reporting Member State) leads the harmonised Part I scientific assessment while all three countries separately assess Part II national aspects in parallel, each then issuing its own authorisation decision through CTIS.
- Is an instance
An academic investigator-initiated, single-country trial in Spain must still be authorised and registered through CTIS, even though no other member state is involved -- CTIS has been mandatory for all new EU trial applications since 31 January 2023, regardless of how many countries participate.
Counter-examples
Looks similar, but isn't
- Not an instance
A trial conducted solely at UK sites is not governed by the CTR/CTIS -- the UK left the EU before Regulation 536/2014 applied and authorises trials domestically through the MHRA under the Medicines for Human Use (Clinical Trials) Regulations 2004.
- Not an instance
A clinical investigation of a medical device with no medicinal product involved falls under the EU's Medical Device Regulation (MDR)/In Vitro Diagnostic Regulation (IVDR) framework, not the CTR -- it is not a CTIS submission.
Editorial commentary
The EU Clinical Trials Regulation — Regulation (EU) No 536/2014, usually shortened to the “CTR” — is the single piece of EU legislation that governs how interventional clinical trials of medicinal products are authorised, run, and reported across the European Union and European Economic Area (EEA). Its operational engine is the Clinical Trials Information System (CTIS), the centralised EU portal through which every such trial must now be applied for, authorised, and publicly registered. The two are effectively inseparable in practice: the CTR is the legal framework, CTIS is the system that implements it, and a sponsor cannot comply with one without using the other.
From the Clinical Trials Directive to the Regulation
The CTR replaced the earlier Clinical Trials Directive 2001/20/EC, which required each EU member state to transpose the Directive into its own national law — producing 27 different national implementations, divergent timelines, and duplicated national-only submissions for any multi-country trial. Because a Regulation is directly applicable EU law rather than something each country transposes separately, the CTR replaced that patchwork with one harmonised procedure. It entered into application on 31 January 2022, the same day CTIS went live.
How CTIS works: one dossier, one portal, many countries
CTIS lets a sponsor submit a single application to run a trial in up to 30 European countries (the EU/EEA member states) at once, rather than filing separately with each national authority. For a multi-country trial, the sponsor’s application designates one country as the Reporting Member State (RMS), which leads a harmonised scientific assessment (Part I of the dossier: benefit-risk, investigational medicinal product data, trial design) shared with every other Member State Concerned (MSC) in the application. Each MSC separately assesses Part II — the aspects that remain nationally specific, such as informed consent arrangements, data protection compliance, investigator and site suitability, and compensation arrangements — largely in parallel with the Part I review, and each then issues its own single combined authorisation decision for its territory through CTIS. Regulatory guidance sets Part I and Part II assessment periods at 45 days each (extendable if the assessing state requests further information), though independent post-launch reviews of CTIS have found actual elapsed time to first decision running somewhat longer in practice than the regulation’s theoretical floor.
Transition timeline: optional, then mandatory, then sole route
- 31 January 2022 – 30 January 2023: sponsors could choose between submitting a new trial application under the old Directive/EudraCT route or the new CTR/CTIS route.
- 31 January 2023: CTIS became mandatory for every new clinical trial application in the EU/EEA — the Directive route closed to new submissions.
- 31 January 2025: the transition period for trials that were still running under the old Directive ended; those trials had to be brought into compliance with the CTR and recorded in CTIS, making CTIS the sole authorisation and registration system for clinical trials in the EU/EEA from that date on.
Older references describing EudraCT or the EU Clinical Trials Register as “the” EU trial registry predate this transition and are now out of date.
Transparency: the public CTIS website
Alongside the secure workspace sponsors and regulators use to manage applications, CTIS operates a public-facing website where authorised trials, their protocols, and (once available) their results/lay summaries are searchable. Sponsors can request temporary deferral of publication for specific documents or data fields containing commercially confidential information or personal data, but the default is public disclosure — a deliberate shift from the more limited public visibility of the EudraCT-era system.
Scope: what is, and isn’t, a CTR/CTIS matter
The CTR covers interventional clinical trials of medicinal products for human use conducted at one or more sites in the EU/EEA. Two common edge cases fall outside it:
- Non-interventional (observational) studies — where the medicinal product is prescribed in the usual manner, in line with its marketing authorisation, and assignment to a treatment isn’t decided in advance by a trial protocol — are not CTR/CTIS trials. See CASRAI’s Non-Interventional Study entry for the distinguishing criteria.
- Medical device trials (with no medicinal product involved) fall under the separate Medical Device Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) clinical-investigation frameworks, not the CTR. See CASRAI’s Investigational Device entry.
Within a CTR/CTIS trial, the application dossier itself draws on other CASRAI-covered standards and documents: the Investigational Medicinal Product Dossier (IMPD) supplies the quality/nonclinical/clinical data on the Investigational Medicinal Product (IMP) being tested, and trial conduct itself still follows ICH Good Clinical Practice (GCP) regardless of which regulatory system authorised the trial.
Worked examples
Example 1. A sponsor plans a Phase III oncology trial across sites in Germany, France, and Poland. It submits one application through CTIS; Germany, as Reporting Member State, leads the harmonised Part I scientific assessment shared with France and Poland as Member States Concerned, while each of the three separately assesses its own Part II national aspects (informed consent, ethics committee opinion, data protection) in parallel. Each country then issues its own single combined authorisation decision through CTIS.
Example 2. An academic investigator at a Spanish university hospital runs a single-country, investigator-initiated trial of a repurposed generic medicine. Even though only one member state is involved, the trial still must be authorised and registered through CTIS — CTIS has been mandatory for all new EU trial applications, regardless of how many countries participate, since 31 January 2023.
Counter-example. A trial conducted solely at sites in the United Kingdom is not a CTR/CTIS matter. The UK left the EU before Regulation 536/2014 became applicable and authorises trials domestically through the MHRA under the Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031, as amended) instead.
References
- 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 — eur-lex.europa.eu, CELEX 32014R0536.
- European Medicines Agency, “Clinical Trials Regulation” and “Clinical Trials Information System (CTIS)” — ema.europa.eu.
- European Commission, Public Health, “Clinical trials — Regulation EU No 536/2014” — health.ec.europa.eu.
- Directive 2001/20/EC of the European Parliament and of the Council (the prior Clinical Trials Directive, repealed on application of the CTR).
Machine-readable encodings
Use in your systems
<role vocab="credit"
vocab-identifier="https://casrai.org/dictionary/"
vocab-term="EU Clinical Trials Regulation (CTR) & CTIS"
vocab-term-identifier="https://casrai.org/dictionary/term/eu-clinical-trials-regulation-and-ctis" />{
"@context": "https://schema.org",
"@type": "DefinedTerm",
"@id": "https://casrai.org/dictionary/term/eu-clinical-trials-regulation-and-ctis",
"name": "EU Clinical Trials Regulation (CTR) & CTIS",
"identifier": "https://casrai.org/dictionary/term/eu-clinical-trials-regulation-and-ctis",
"description": "A clinical trial is governed by the EU Clinical Trials Regulation (Regulation (EU) No 536/2014, the \"CTR\") -- and therefore must be authorised and registered through the EU's Clinical Trials Information System (CTIS) -- when it (1) is an interventional trial (not a purely observational/non-interventional study), (2) tests a medicinal product for human use (not a medical device, which falls under the MDR/IVDR instead), and (3) includes at least one trial site in an EU/EEA member state. Since CTIS became the sole authorisation and registration route on 31 January 2025 -- completing a three-year transition away from the prior Clinical Trials Directive 2001/20/EC and the EudraCT/EU Clinical Trials Register it used -- this applies whether the trial runs in a single member state or spans multiple countries via one application, one Reporting Member State (RMS), and any number of other Member States Concerned (MSC).",
"inDefinedTermSet": "https://casrai.org/dictionary/domain/clinical-research#set",
"url": "https://casrai.org/dictionary/term/eu-clinical-trials-regulation-and-ctis",
"sameAs": [],
"license": "https://creativecommons.org/licenses/by/4.0/",
"publisher": {
"@id": "https://casrai.org/#organization"
},
"dateModified": "2026-07-18T01:44:49",
"inLanguage": "en"
}
