Safety reporting during clinical medicinal trials

The sponsor of a clinical trial must ensure that information on adverse events, adverse reactions, protocol deviations and other safety issues during clinical trials are recorded and reported.

The investigator is responsible for assessing causality for all events and must report all serious adverse events to the sponsor without undue delay and within 24 hours, unless risk-adapted adverse event management is described in the protocol.

The sponsor is responsible for assessing whether a serious event received from the investigator is expected, and immediately report all suspected serious unexpected adverse reactions (SUSARs) directly to the European EudraVigilance database in accordance with the Article 42 of the Regulation. Read more under Reporting suspected serious unexpected adverse reactions to the EudraVigilance database for clinical trials with medicinal products.

Once a year, the sponsor must prepare and submit an annual safety report (ASR/DSUR) in CTIS. In the ASR, the sponsor must, based on cumulative safety information, evaluate the safety of the trial and assess whether the benefit/risk ratio has changed and whether the trial can continue. The ASR must be prepared for all trials. Read more under Reporting annual safety reports in clinical trials.

Other safety measures during clinical trial, such as urgent safety measures, serious breaches and premature end of trial must also be submitted in CTIS.

For further information on legal requirements and guidance on safety reporting in clinical trials, please refer to Regulation (EU) No 536/2014 of 16 April 2014 on clinical trials on medicinal products for human use and the European Commission's question and answer document available on the European Commission's website EudraLex Volume 10. In Denmark, there are no special national requirements for safety reporting in clinical trials.

Assessing serious adverse events and reactions in a clinical trial

It is essential for the safety of trial participants and data integrity that the sponsor, investigator and other relevant clinical trial staff understand and are trained in the processes of assessing, recording and reporting adverse events and reactions in clinical trials. The processes for assessment of adverse events and the definitions of relevant terms must therefore be adequately described in the protocol.

The process for assessing whether an event is serious (SAE), related (SAR) and whether the serious adverse reaction is unexpected (SUSAR) is described in the figure below. These processes must be in place irrespective of whether risk-adapted recording and reporting of adverse events is implemented.

Link to flow diagram of safety reporting during clinical trials

The protocol should always describe which adverse reactions and events the investigator should report to the sponsor and when this should be done after the adverse reaction/event has been identified.

For further guidance on the assessment of events and any risk adjustment of adverse reaction management, please refer to the Danish Medicines Agency's guidance risk-adapted adverse reaction recording and reporting in clinical trials of medicinal products under Regulation (EU) No 536/2014.

Change log: 

November 2024: Updated version of the DKMA guidance on risk-adapted recording and reporting (V. 2.0) (central version link).