Adverse event reporting comprises the regulated collection, documentation, evaluation, and transmission of safety information on medicinal products. Which entity is informed and which data are transmitted depends on whether a medicinal product is being investigated in a clinical trial or is already authorized. The reporting pathways for investigator sites, sponsors, marketing authorization holders, and authorities must therefore be clearly separated from each other.
Reporting pathway in the clinical trial
In clinical trials, the investigator site is the first point where safety information arises. The investigator documents adverse events and the laboratory abnormalities defined as safety-relevant in the protocol. Regulation (EU) No 536/2014 provides that all adverse events are recorded, provided the protocol contains no reasoned deviating rule. The protocol further specifies which details are required, how follow-up information is obtained, and which timeframes apply for non-serious events.
The investigator fundamentally forwards serious adverse events to the sponsor without undue delay; the EU practical guideline specifies for this at the latest 24 hours after obtaining knowledge, provided the protocol does not require immediate reporting for specific events. The sponsor is not merely a transmitter. The sponsor evaluates the case including causality and expectedness, consolidates safety information from all investigator sites, and decides whether a regulatory safety report is required.
Sponsor, SUSAR and EudraVigilance
If a case fulfills the criteria of a suspected unexpected serious adverse reaction, SUSAR, the sponsor reports the relevant information electronically to the designated EudraVigilance database. For fatal or life-threatening SUSARs, a timeframe of a maximum of seven days begins upon the sponsor’s knowledge; for other SUSARs it is a maximum of 15 days. The sponsor also submits an annual safety report for each investigational medicinal product it uses via the EU database.
In addition to SUSAR reporting, there are other safety pathways. Unexpected events that influence the benefit-risk balance of the trial, but are not SUSARs, are reported to the concerned Member States via CTIS. The separation is important: not every safety-relevant event is an individual case report to EudraVigilance, and not every AE documented at an investigator site directly reaches an authority. The sponsor controls the medical evaluation and the regulatory output channel.
For inquiries, follow-up reports, and annual safety reporting, these pathways must interlock in a documented manner.
Distinction from post-authorization reporting
After authorization, the starting point of reporting shifts. Patients, healthcare professionals, and other sources can report suspected adverse drug reactions to national systems or to the marketing authorization holder. The marketing authorization holder consolidates the suspected cases that become known to it and transmits the Individual Case Safety Reports electronically via EudraVigilance. Decisive here is the pharmacovigilance of a marketed medicinal product, not the protocol-based safety data flow of a single study protocol.
Post-authorization reporting also includes the continuous evaluation of aggregated data. Periodic Safety Update Reports, PSURs, assess the benefit-risk balance at defined time points. A signal is, in turn, not an automatically confirmed adverse reaction, but information from one or more sources that justifies further review of a possible relationship. EudraVigilance supports both the transmission of individual cases and the monitoring of safety data in the European pharmacovigilance system.
Relevance for clinical trials
In study practice, responsibilities, availability, and data pathways must be established before the first included participant. Investigators need clear specifications for the immediate forwarding of serious cases, for documentation in the case report form, and for the follow-up reporting of new information. The sponsor needs processes for triage, medical evaluation, coding, data reconciliation, and timely transmission. Incomplete dates, contradictory causality assessments, or untracked follow-up information jeopardize the quality of the safety evaluation.
Full-service CROs such as Mediconomics provide support with the safety management plan, training of investigator sites, monitoring of incoming cases, and coordination of pharmacovigilance, monitoring, data management, and regulatory affairs. Specific services are the plausibility check of case data, the tracking of queries, the preparation of regulatory reports, and the alignment of safety information with investigator information and study reports. Thus, investigator-to-sponsor and sponsor-to-authority processes remain traceably separated.
Frequently Asked Questions (FAQ)
Does an investigator report a SUSAR directly to EudraVigilance?
No. The investigator reports the relevant events to the sponsor. The sponsor evaluates the case and transmits SUSARs electronically to EudraVigilance.
Are all adverse events in a clinical trial reported to authorities?
No. Events are documented at the investigator site and transmitted to the sponsor according to the protocol. Only specific evaluated safety information triggers the respective regulatory reporting pathways.
What is the difference between CTIS and EudraVigilance?
CTIS is the clinical trials information system according to the Clinical Trials Regulation. EudraVigilance is the European database for electronic safety reports, including for SUSARs and suspected cases post-authorization.
Regulatory references
- Regulation (EU) No 536/2014, Articles 40 to 43 and 53 – regulates database, SUSARs, annual safety reports, and other events.
- ICH E6(R3) “Good Clinical Practice” – describes responsibilities of the investigator and sponsor for serious events.
- ICH E2B(R3) – defines data elements and message standards for individual case safety reports.
- Directive 2001/83/EC, Title IX – forms the Union law framework of post-authorization pharmacovigilance.
- Regulation (EC) No 726/2004, Article 24 – anchors the EudraVigilance database.