Reporting safety information on clinical trials

Clinical trial sponsors must report information on the safety of clinical trial participants to the European Union (EU) Member States and European Economic Area (EEA) countries throughout the lifecycle of a clinical trial. Guidance is available from the European Medicines Agency (EMA) to help clinical trial sponsors comply with their reporting obligations.

Requirements differ depending on whether the clinical trial was authorised under the Clinical Trials Directive or the Clinical Trials Regulation. See Transition period for clinical trial sponsors.

Reporting requirements under the Clinical Trials Regulation

For clinical trials authorised under the Clinical Trials Regulation, sponsors must report the information below for assessment by the relevant EU and EEA authorities.

TYPE OF INFORMATION	DESCRIPTION	WHERE TO REPORT
Suspected unexpected serious adverse reactions (SUSARs)	Adverse reactions due to medicines administered in a clinical trial that are unexpected and serious.	EudraVigilance
Unexpected events	Events that affect the benefit-risk balance of a clinical trial that were unforeseen, e.g. an unexpected increase in the incidence of expected serious adverse reactions that may be clinically important. Unexpected events do not include SUSARs.	Clinical Trials Information System (CTIS)
Urgent safety measures	Measures taken to protect clinical trial subjects due to an unexpected event that is likely to seriously affect the benefit-risk balance of the clinical trial
Serious breaches	Transgressions against the clinical trial protocol or the Clinical Trials Regulation that are likely to significantly affect the safety and rights of a subject or the reliability and robustness of the data generated in the clinical trial
Annual safety reports	Yearly updates on the safety of each investigational medicinal product used in a clinical trial

These rules came into effect on 31 January 2022.

More information:

• Clinical Trials Regulation (Chapters VII and VIII )
• Reporting SUSARs to EudraVigilance
• Clinical Trials Information System
• Clinical Trials Information System: training and support

Reporting requirements under the Clinical Trials Directive

For clinical trials authorised under the Clinical Trials Directive, sponsors must report the information below for assessment by the relevant EU and EEA authorities.

For SUSARs, they should report to EudraVigilance. For some countries, sponsors should report to national ethics committees (they are advised to review the relevant national legislation). 

SUSARs should be reported to EudraVigilance instead of separately to national competent authorities in each EU / EEA country where related clinical trials are running. This rule came into effect on 31 January 2022. 

All other safety related information should be reported to the national competent authorities of the EU Member States / EEA countries and ethics committees via national processes.

More information:

• European Commission: Detailed guidance on the collection, verification and presentation of adverse event / reaction reports arising from clinical trials on medicinal products for human use (‘CT-3’) (Sections marked as 'final arrangements')
• Clinical Trials Directive
• Reporting SUSARs to EudraVigilance

Reporting SUSARs to EudraVigilance

Sponsors must complete the following steps before they can submit SUSARs to Eudravigilance:

• Obtain a medical dictionary for regulatory activities (MedDRA) licence if required or confirm if the fee waiver is applicable for your organisation
• Create an active EMA account in EMA Account Management
• Register the organisation in EMA’s Organisation Management Service (OMS), if it has not already been registered
• Designate a person responsible for EudraVigilance (they should request the EudraVigilance role "responsible person (RP)" in EMA Account Management)
• Choose one of the following reporting modes:
  • EVWEB, whereby sponsors use EudraVigilance for creating and sending SUSARs
  • Gateway, whereby sponsors send SUSAR from their own database to Eudravigilance
• Request 'EudraVigilance user roles' in the EMA Account Management portal 
• Train users in EudraVigilance, if the organisation chooses to use EVWEB (at least one person per organisation must have a notification of successful completion of the competency assessment or knowledge evaluation before the organisation can initiate electronic submission of SUSARs in EudraVigilance)
• Create a clinical trial application in CTIS or in the European Union Drug Regulating Authorities Clinical Trials (EudraCT)

Those who cannot report SUSARs to EudraVigilance due to lack of resources may be able to report them directly to the national competent authority of the Member State or EEA country where they occurred. The national competent authority then takes responsibility for reporting the SUSARs to EudraVigilance. This is only possible with prior agreement from the national competent authority.

Targeted training opportunities are available from EMA to support clinical trials sponsors in using EudraVigilance:

• Virtual live hands-on training courses for clinical trial sponsors
• Online training and competency assessment for non-commercial sponsors

More information and guidance:

• EudraVigilance
• EudraVigilance: how to register
• EudraVigilance training and support

EudraVigilance - EVWEB user manual

Reference Number: EMA/501718/2018 Version 1.7