Reporting of adverse reactions in clinical trials
Clinical trial sponsors are obliged to immediately report suspected unexpected serious adverse reactions (SUSARs) that arise in clinical trials.
The following applies to immediate reporting of SUSARs to the Danish Medicines Agency:
- SUSARs arising from clinical trials in Denmark whose conduct have been authorised by the Danish Medicines Agency must be reported immediately to the Danish Medicines Agency in accordance with the definitions and time frames specified in the Danish executive order on clinical trials (no. 295 of 26 April 2004) and EU directive 2001/20/EC.
- SUSARs arising from clinical trials with the same protocol (same EudraCT number) in other EU/EEA countries must also be reported immediately to the Danish Medicines Agency in accordance with the Danish executive order on clinical trials (no. 295 of 26 April 2004) and EU directive 2001/20/EC.
- SUSARs from third countries or from other clinical trials with the same investigational medicinal product should not be reported to the Danish Medicines Agency. If they affect ongoing trials in Denmark, it is the usual practice to submit a protocol amendment as well as other relevant documentation with a description of the background for the amendment (including the SUSAR) in the cover letter.
All serious adverse reactions (SARs) from the entire trial must appear from the annual report on the trial subjects’ safety. This includes expected as well as unexpected serious adverse reactions (SARs and SUSARs). In our Guideline for applications for authorisation of clinical trials of medicinal products in humans, chapter 12.4, you can find detailed information about the Annual Safety Report.
All important adverse events from the trial must appear from the final reporting of trial results in the EudraCT database in accordance with the EU guideline 2008/C168/02
An adverse reaction, which is exclusively suspected to be related to non-investigational medicinal products, and where there is no interaction with the investigational medicinal products, should not be reported in relation to the trial but should be reported as a spontaneous adverse reaction. Read more about the reporting of spontaneous adverse reactions on our website under side effects from medicines.
Adverse reactions arising in non-interventional trials must also be reported as spontaneous reports because these trials are not regulated by the clinical trials regulation.
SUSARs must be unblinded before submission, and it must be clearly specified which investigational medicinal product the patient has received. Moreover, it must also be clearly stated that the investigator and/or sponsor has assessed that the adverse reaction is associated with the investigational medicinal product and why the adverse reaction is serious. If the investigator has assessed that the adverse reaction is related to the investigational medicinal product, the sponsor cannot downgrade this assessment. Both the assessment of the investigator and the sponsor can be included in the SUSAR report.
In connection with the submission of follow-up information, the new information must appear clearly from the report, and before the submission it should be considered carefully whether the new information is relevant. For example, minor changes of dates and typographical corrections are not relevant information, and laboratory results should be accompanied by a conclusion concerning the relevance to the current case. You can read more about the EU Commission's clinical trials guidelines in EudraLex - Volume 10, chapter II
In our Guideline for applications for authorisation of clinical trials of medicinal products in humans, chapter 12 you can find detailed information about how to handle and report adverse reactions in clinical trials.
Below you can find more information about how to report adverse reactions in clinical trials.
Note that special guidelines apply to reporting adverse reactions in clinical trials in animals
How do I report adverse reactions in clinical trials?
Sponsors are encouraged to report SUSARs electronically, both SUSARs occurring in clinical trials in Denmark and clinical trials with the same EudraCT number in other EU countries. Electronic reporting is possible either via EudraVigilance or via the Danish Medicines Agency's e-form.
The Danish Medicines Agency's recommends non-commercial sponsors without access to EudraVigilance to report SUSARs using the e-form Reporting of suspected unexpected serious adverse reactions (SUSARs) seen in clinical trials
Commercial sponsors are encouraged to report SUSARs via EudraVigilance. Read more about electronic reporting of SUSARs via EudraVigilance below and in Prerequisites for submitting SUSARs via E2B.
Electronic reporting of adverse reactions via EudraVigilance
To be able to report SUSARs electronically to the Danish Medicines Agency, the Sponsor's Sender ID must be registered in our system and the Sponsor must have tested the connection with the EMA and the Danish Medicines Agency. Read more about practical information in connection with testing and configuration of the Sender ID in Prerequisites for submitting SUSARs via E2B.
If you submit SUSARs via EudraVigilance, you should send the report to both the Danish Medicines Agency (DKMAEUDRA) and the EMA (EVCTMPROD) via E2B.
Only suspected unexpected serious adverse reactions (SUSARs) related to the investigational medicinal products of clinical trials and falling under directive 2001/20/EC must be reported by the sponsor to the EudraVigilance Clinical Trial Module (EVCTM).
Adverse reactions from clinical trials conducted in compliance with directive 2001/20/EC which are suspected only to be related to non-investigational medicinal products (or another medical product not covered by the clinical trial) and where there is no interaction with the investigational medicinal products are to be considered as spontaneous reports and must therefore be reported to the EudraVigilance Post-Authorisation Module (EVPM).
Reporting adverse reactions in clinical trials in animals
The sponsor is obliged to immediately report serious adverse reactions and serious adverse events occurring in veterinary trials to the Danish Medicines Agency.
You can find more information in Guidelines on application for clinical trials of veterinary medicinal products in animals from March 2012. You will find the form for reporting adverse reactions in clinical trials of veterinary medicinal products in animals in Annex 5.