Investigators and sponsors are required to report adverse reactions and information on the safety of medicines in clinical trials in accordance with Regulation (EU) No. 536/2014 concerning pharmacovigilance definitions.

• Read more about pharmacovigilance or the main definitions of adverse reactions that must be reported. (link to another page?)

Procedure for reporting adverse reactions

Adverse reactions and serious adverse reactions – reporting by the investigator to the sponsor

The investigator must keep records of all adverse reactions and abnormal findings, unless otherwise specified in the protocol.

• Serious adverse reactions must be reported to the sponsor without delay and no later than 24 hours after the investigator becomes aware of the reaction.

• If adverse reactions occur after the clinical trial has ended, the investigator must report them to the sponsor without delay.

• The sponsor must keep detailed records of all adverse reactions reported by the investigator.

For non-interventional studies, an exemption from recording adverse reactions may be granted following a thorough risk assessment. The sponsor must specifically state and justify the request for an exemption in the protocol.

Suspected unexpected serious adverse reactions (SUSARs) – reporting by the sponsor to the European Medicines Agency (EMA)

The sponsor of a clinical trial must report the following SUSARs to the EudraVigilance database without delay:

• All SUSARs occurring in the clinical trial, whether at a trial site in the EEA or in a third country (a country outside the EEA).

• All SUSARs relating to the same active substance of the investigational medicinal product in a clinical trial conducted exclusively in a third country, regardless of the pharmaceutical form, strength or indication being investigated, where the sponsor is:

  • the same sponsor, another sponsor belonging to the same parent company as the trial sponsor, or a party jointly developing a medicine with the trial sponsor under a formal agreement.

• All SUSARs relating to the investigational medicinal product in animals or humans that occur after the clinical trial has ended and of which the sponsor becomes aware.

SUSAR reporting timelines depend on the seriousness of the adverse reaction

If the suspected unexpected serious adverse reaction is:

If necessary, section 2.4 of Annex III to the Clinical Trials Regulation (CTR) allows the sponsor to submit an incomplete report to ensure that information about a SUSAR is reported within the required timeframe. A complete report must be submitted later. The same section provides information on how to report follow-up information relating to suspected unexpected serious adverse reactions.

The assessment of whether an adverse reaction is unexpected is based on the available safety information. SUSARs must be reported unblinded, while those responsible for conducting the trial, such as the investigator, must remain blinded.

Reporting to the EudraVigilance database

The sponsor, or the party to whom the sponsor has delegated SUSAR reporting, must be registered as a sender in the EudraVigilance database. Non-commercial sponsors, such as universities and university hospitals, that do not have access to EudraVigilance may contact the Icelandic Medicines Agency (IMA), which will submit the SUSAR report to the database if the case occurs in Iceland.

In such cases, a request and justification must be submitted with the clinical trial application. Reports must then be sent to IMA using the CIOMS form. Please do not send the request by email, as it contains personally identifiable data. The report must be sent to IMA via Signet Transfer.

Suspected unexpected serious adverse reactions (SUSARs) – reporting by the sponsor to investigators