Clinical trials in human medicines

The European Medicines Agency (EMA) relies on the results of clinical trials carried out by pharmaceutical companies to reach its opinions on the authorisation of medicines. Although clinical trials are authorised at national level in the European Union (EU), EMA plays a key role in further developing the EU as a competitive centre for innovative clinical trials, and in maintaining IT systems for the coordination of clinical trials.

Clinical trials are studies intended to discover or verify the effects of one or more investigational medicines.

The Clinical Trials Regulation aims to ensure that the rights, safety and well-being of trial participants are protected and the results of clinical trials are credible.

Regardless of where they are conducted, all clinical trials included in applications for marketing authorisation for human medicines in the European Union (EU) / European Economic Area (EEA) must have been carried out in accordance with the requirements set out in Annex 1 of Directive 2001/83/EC. This means that:

• clinical trials conducted in the EU / EEA have to comply with EU clinical trial legislation;
• clinical trials conducted outside the EU / EEA have to comply with ethical principles equivalent to those set out in the EEA, including adhering to international good clinical practice and the Declaration of Helsinki.

Also on this topic

• Accelerating Clinical Trials in the EU (ACT EU)
• Data submission on investigational medicines: guidance for clinical trial sponsors
• Reporting safety information on clinical trials
• Clinical Trials Regulation
• Clinical Trials Information System
• Clinical Trials Information System: training and support

EMA's role

EMA's Committee for Medicinal Products for Human Use (CHMP) assesses marketing authorisation applications for human medicines designed to be marketed in the EU. CHMP reviews the clinical trial data included in the application. 

CHMP assessments are based solely on scientific criteria. They determine if a medicine meets the EU legislation requirements for quality, safety and efficacy.

Clinical trial data is included in clinical-study reports that form a large part of application dossiers. Applicants for marketing authorisation include pharmaceutical companies and small and medium enterprises.

Collaboration and guidance

EMA collaborates with Member States to uphold the principles of good clinical practice.

It provides scientific advice and protocol assistance to medicine developers upon request. 

EMA has a policy for publishing clinical reports that pharmaceutical companies submit to support their regulatory applications.

Support for clinical trials

EU Member States and EEA countries assess applications for clinical trial authorisations at national level. 

EMA supports this process by managing the Clinical Trial Information System, where sponsors submit their clinical trial information for authorisation. 

During a clinical trial, sponsors must report any safety information.

EMA also maintains the EudraCT database.

Furthermore, EMA co-leads the Accelerating Clinical Trials in the EU (ACT EU) initiative together with the Heads of Medicines Agencies (HMA) and the European Commission. ACT EU aims to create a favourable environment for clinical research in the EU / EEA.

For more information, see: 

• Committee for Medicinal Products for Human Use (CHMP)
• Clinical data publication
• European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) database
• Reporting safety information on clinical trials
• Accelerating Clinical Trials in the EU (ACT EU)
• Clinical Trials Regulation

Management of clinical trials impacted by the war in Ukraine

Sponsors can adjust the way they run clinical trials that have been affected by the war in Ukraine using the experience gained during the COVID-19 pandemic. They can also apply the approaches and flexibilities agreed in the context of the pandemic.

The European Commission, EMA and the Heads of Medicines Agencies (HMA) issued this initial advice for sponsors on 30 March 2022:

• Advice to sponsors on managing the impact of the war in Ukraine on clinical trials(30/03/2022)

Additional recommendations for sponsors are available from the Clinical Trials Coordination Group (an HMA group uniting clinical trials experts):

• Heads of Medicines Agencies - Recommendation to sponsors on managing the impact of the war in Ukraine on clinical trials

Guidance is also available from EMA's Biostatistics Working Party on actions sponsors of affected clinical trials can take to help ensure the integrity of their studies and the interpretation of the study results while safeguarding the safety of trial participants as a first priority:

• Points to consider on the impact of the war in Ukraine on methodological aspects of ongoing clinical trials

EMA strongly encourages sponsors to capture data affected and unaffected by the war, and to use the 'estimand framework' described in the ICH E9 (R1) guideline for dealing with events impacting the trial:

• ICH E9 statistical principles for clinical trials

Guidance on clinical trial management during the COVID-19 pandemic is available below.

• Guidance on clinical trial management during the COVID-19 pandemic
• Implications of Coronavirus disease (COVID-19) on methodological aspects of ongoing clinical trials

EMA advises sponsors to also check any guidance available at national level.

Sponsors with specific questions relating to EU guidance can contact EMA using the Send a question form. Questions relating to national guidance should be addressed to the relevant national authority.

Sponsors can also contact either EMA or the national competent authorities for scientific advice on:

• methodological aspects relating to their trials;
• the use of affected clinical trial results for regulatory purposes.

Clinical trial management for public health emergencies

Support in preparation for and during public health emergencies

EMA's Emergency Task Force (ETF) can provide support to clinical trial sponsors for all medicines intended to target a potential or declared public health emergency. This is in line the Regulation on EMA's Reinforced Role (Regulation (EU) 2022/123). 

This support includes:

• Setting up joint multinational clinical trials
• Acting as a sponsor or co-sponsor of a trial
• Deciding on which protocol to follow

Interested clinical trial sponsors should send their proposals to [e-mail].

They should include the study protocol and specify in which Member State(s) they intend to run clinical trials, if already known.

The ETF works closely with EMA’s partner organisations in the EU to support study sponsors and the conduct of larger multinational trials.

These partner organisations include:

• Heads of Medicines Agencies' (HMA) Clinical Trials Coordination Group (CTCG);
• European Commission's Clinical Trials Advisory Group (CTAG);
• European Health Emergency Preparedness and Response Authority (HERA)

A report is available recommending EU-level actions to improve the set-up and conduct of clinical trials during public health emergencies.

The recommendations seek to address issues seen in the COVID-19 pandemic and outbreak of mpox disease with setting up large enough clinical trials across multiple EU Member States. These are needed to rapidly gather sufficient high-quality evidence to support decision-making by health authorities. 

The report results from a lessons-learned workshop on clinical trials in emergencies held by EMA's ETF and the European Commission with national competent authorities, ethics committees and academic experts.

Report of the EMA/ETF workshop on Lessons Learned on Clinical Trials in Public Health Emergencies

Reference Number: EMA/340269/2023

For more information, see:

• European Medicines Agency / Emergency Task Force and European Commission workshop on lessons learned on clinical trials in public health emergencies (09/06/2023)
• Scientific advice and protocol assistance: Medicines intended for a disease causing public health emergency
• Public health threats  

Guidance for clinical trial sponsors during the COVID-19 pandemic

Guidance has been available for clinical-trial sponsors on managing clinical trials and participants during the COVID-19 pandemic:

• Good clinical practice: Guidance on clinical trial management during the COVID-19 pandemic

This covered how to deal with the extraordinary situations that the pandemic presented and specific advice on clinical trials for potential COVID-19 treatments.

Guidance has also been available for sponsors of affected clinical trials to help ensure the integrity of their studies and the interpretation of the study results while ensuring the safety of trial participants:

• Implications of Coronavirus disease (COVID-19) on methodological aspects of ongoing clinical trials

In line with this guidance, EMA has been flexible and pragmatic during the assessment of affected clinical trial data submitted as part of marketing authorisation applications.

Accelerating Clinical Trials in the EU (ACT EU)

The Accelerating Clinical Trials in the EU (ACT EU) initiative aims to develop the EU further as a competitive centre for innovative clinical research. 

The initiative builds on the Clinical Trials Regulation (CTR) and Clinical Trials Information System's (CTIS) launch on 31 January 2022. It aims to deliver on the clinical trial innovation recommendations of the European medicines agencies network strategy and the European Commission’s Pharmaceutical strategy for Europe.

For more information, see: 

• Accelerating Clinical Trials in the EU (ACT EU)

Decentralised clinical trials

Decentralised clinical trials aim to facilitate participation in clinical trials by offering maximum flexibility and convenience.

For instance, they can enable participants to:

•    have health visits at home;
•    receive study medicine shipments at home;
•    provide their consent electronically

The Clinical Trials Coordination Group (CTCG) is overseeing a project on decentralised clinical trials called the EU Decentralised Clinical Trials project (EU DCT project).

The project aims to identify:

•    innovative designs and methodologies for clinical trials;
•    opportunities provided by decentralised clinical trials in Europe;
•    the challenges that decentralised clinical trials provide.

The project began in March 2022.

The project delivered a recommendation paper on the use of decentralised elements in clinical trials in December 2022.

• Recommendation paper on decentralised elements in clinical trials

The development of this paper took account of the perspectives of all areas of the research community on decentralised clinical trials, including at a multi-stakeholder workshop hosted by ACT EU in October 2022.

Guidance on complex clinical trials

Guidance is available for clinical trial sponsors, clinicians engaged in clinical trials and marketing authorisation applicants on planning and conducting complex clinical trials: 

• Complex clinical trials – questions and answers

The guidance covers the following topics: 

• Planning and conducting complex clinical trials
• Designing and conducting master protocols
• Methods for clinical trial analysis (e.g. Bayesian approaches)
• Biomarkers and their assays
• Reporting trial information to regulatory authorities
• Transparency

EMA, the European Commission and the Heads of Medicines Agencies (HMA) published this guidance under the ACT EU initiative. 

It aims to strengthen the link between scientific advice offered by regulators and innovative clinical research.

They published the guidance in May 2022.

For more information, see: 

• Accelerating Clinical Trials in the EU (ACT EU)
• EudraLex - clinical trial guidelines

Clinical Trials Regulation and the Clinical Trials Information System

The Clinical Trials Regulation (Regulation (EU) No 536/2014) entered into application on 31 January 2022, repealing the Clinical Trials Directive (EC) No. 2001/20/EC. 

The Regulation is part of a broad initiative to transform the EU / EEA clinical trials environment in support of large clinical trials in multiple European countries, to the benefit of medical innovation and patients.

For more information, see Clinical Trials Regulation.

As of 31 January 2025, any ongoing trials approved under the Clinical Trials Directive fall under the Clinical Trials Regulation.

For more information, see:

• Clinical Trials Regulation: Transition period for clinical trial sponsors

Clinical Trials Information System

The Clinical Trials Information System (CTIS) supports interactions between clinical trial sponsors (researchers or companies that run clinical trials and collect and analyse the data) and regulatory authorities in the EU Member States and EEA countries, throughout the lifecycle of a clinical trial.

CTIS went live with a searchable public website on 31 January 2022.

It serves to implement EU pharmaceutical law in the Clinical Trials Regulation - Regulation (EU) No 536/2014.

For more information, see: 

• Clinical Trials Information System
• Clinical Trials Information System (CTIS): training and support

EudraCT database and the EU Clinical Trials Register

EMA is responsible for the development, maintenance and coordination of the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database and its interface, the European Union Clinical Trials Register.

The EudraCT database includes data on:

• Interventional clinical trials run in the EU / EEA under the Directive 2001/20/EC
• Interventional clinical trials run outside the EU / EEA that are part of a paediatric investigation plan (PIP), as required by Article 41 of the Paediatric Regulation (Regulation (EC) No 1901/2006)
• Interventional clinical trials run outside the EU / EEA that are in scope of Articles 45 and 46 of the Paediatric Regulation (Regulation (EC) No 1901/2006)

As of 31 January 2023, all initial clinical trial applications in the EU / EEA must be submitted through the Clinical Trials Information System.

The EudraCT database remains available for uploading the following:

• Amendments, trial statuses and results of trials that are already in EudraCT
• Third country files of trials conducted exclusively outside of the EU / EEA that are part of a paediatric investigation plan (PIP) or are in scope of Article 46 of the Paediatric Regulation (EC) No 1901/2006. 

As of 31 January 2025, any ongoing trial in the EU / EEA falls under the Clinical Trials Regulation. For more information, see Clinical Trials Regulation: Transition period for clinical trial sponsors.

A subset of this data is available through the European Union Clinical Trials Register, which EMA manages on behalf of EU and EEA Member States. Users are able to view protocol and result information regarding:

• phase-II to phase-IV adult clinical trials where the investigator sites are in the EEA;
• any clinical trials in children with investigator sites in the EU and any trials that form part of a PIP including those where the investigator sites are outside the EU.

Information about the results of public clinical trials is shown in the European Union Clinical Trials Register - if posted by the relevant sponsor on the EudraCT database. 

Requirements for sponsors on reporting of results

In line with European Commission guideline 2012/C 302/03, sponsors are required to post results of all clinical trials in EudraCT that are completed globally.

They need to post results within 12 months of completing the trial for clinical trials conducted in adults, and within six months for clinical trials in children.

In July 2019, EMA published a letter co-signed by the European Commission and the Heads of Medicines Agencies (HMA) reminding all sponsors of their obligation to post on EudraCT the results of completed trials:

Joint letter by the European Commission, EMA and HMA to stakeholders regarding the requirements to provide results for authorised clinical trials in EudraCT

Reference Number: Ref. Ares(2019)3933941 -20/06l2019

As of June 2022, 81% of clinical trials are compliant with this requirement in EudraCT.

Between April 2019 and June 2022, the compliance rate rose:

• from 24% to 64% for non-commercial sponsors;
• from 77% to 86% for commercial sponsors.

EMA and national competent authorities enabled these compliance rates through reminders sent to clinical trials sponsors. A full list of clinical trials for which sponsors did not follow up on these reminders is available on the European Clinical Trials Register.

From October 2020, sponsors can also post results of clinical trials that ended prematurely, whether they were approved but never started or started but terminated early. Sponsors should provide the reasons for the premature end and any partial results, if available.

For more information, see the EudraCT and European Union Clinical Trials Register websites.

Clinical trials conducted in countries outside the EU

Clinical trials conducted outside the EU but submitted in an application for marketing authorisation in the EU have to follow the principles which are equivalent to the provisions of the relevant EU legislation.

In 2012, the Agency published the final version of this paper:

Reflection paper on ethical and good-clinical-practice aspects of clinical trials of medicinal products for human use conducted outside of the European Union (EU) / European Economic Area and submitted in marketing-autho...

Reference Number: EMA/121340/2011

This paper aims to strengthen existing processes to provide assurance that clinical trials meet the required ethical and GCP standards, no matter where in the world they have been conducted.

The number of clinical trials and clinical trial subjects outside Western Europe and North America has been increasing for a number of years. More information is available in this document:

Clinical trials submitted in marketing-authorisation applications to the European Medicines Agency: Overview of patient recruitment and the geographical location of investigator sites

Reference Number: EMA/INS/GCP/676319/2012

Requirements for sponsors on reporting of trials conducted outside of the EU/EEA

Sponsors are required to submit information in EudraCT on clinical trials conducted exclusively outside of the EU / EEA, if they are: 
•    part of an agreed paediatric investigation plan (PIP); 
•    in scope of Article 46 of the Paediatric Regulation (Regulation (EC) No 1901/2006).

For more information, see the EudraCT Frequently Asked Questions.

Clinical Trials Coordination Group

The Clinical Trials Coordination Group (CTCG) is a working group of the Heads of Medicines Agencies.

The CTCG aims to help make the EU / EEA more attractive for clinical trials activities.

It is responsible for harmonising and optimising the regulatory environment while assuring the protection of rights, safety and wellbeing of clinical trial participants and ensuring the generation of robust data.

The group is composed of experts in the classification, assessment and oversight of clinical trials from national agencies.

The Clinical Trials Coordination Group replaced the Clinical Trials Facilitation and Coordination Group. 

Clinical Trials Highlights

The Clinical Trials Highlights newsletter covers topics such as Accelerating Clinical Trials in the EU (ACT EU) and the development of CTIS.

Issues from July 2023 (Issue 15) onwards are available at the link below: 

• Clinical Trials Highlights: Issue 15 onwards

Previous issues are available on EMA's website in PDF format: 

• Clinical Trials Highlights: Issues 1 - 14

Use the link below to receive Clinical Trials Highlights by email:

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