An Adverse Event of Special Interest, AESI for short, is a pre-specified adverse event of special observational interest. The special attention arises from the known or plausibly expected safety profile of a medicinal product, its active substance class, the target population or from previous findings. An AESI is not an independent legal severity category, but an operational safety category with a defined collection and evaluation pathway.
Why events are specified as AESI
The specification of an AESI is done prospectively. Starting points can be non-clinical findings, known class effects, earlier clinical data, findings on a similar medicinal product or medically justified risks in the target population. The event is described as precisely as possible so that study centers and safety functions recognize comparable cases. This can include clinical criteria, laboratory parameters, diagnoses, MedDRA terms or specified examinations.
The AESI list does not focus exclusively on confirmed medicinal product risks. It can also cover hypotheses whose occurrence, frequency or course is to be specifically investigated. An event does not become an AESI because it appears particularly striking in a single case. What is decisive is its prior definition. This definition enables cases to be brought together systematically, follow-up information to be obtained uniformly and results to be evaluated across study centers and trials.
Specification in the protocol and safety management plan
The protocol should specify the scope and operational requirements for each AESI. This includes the event definition, the observation period, required diagnostics, the information to be collected, the reporting pathways and the procedure for follow-up information. The safety management plan translates these requirements into workflows for study centers, sponsor and involved service providers. In this way, it becomes clear which cases must be reviewed or medically followed up particularly quickly.
The specification does not replace an individual case assessment. Each AESI continues to be evaluated with regard to severity, causality and expectedness. Depending on the protocol, additional laboratory values, imaging diagnostics or the evaluation by an independent expert committee may be foreseen. Aggregated AESI analyses should consider the denominator of exposed persons, the time of occurrence, risk factors and alternative explanations. Only in this way can a professionally robust safety assessment be derived from an accumulation.
If definitions are adjusted during a trial, the reason, version and impact on already collected data must be transparently documented. Otherwise, the comparability of the analyses can be impaired.
Differentiation from SAE and signal
An SAE is a serious adverse event that meets defined consequences or criteria, such as death, life-threatening situation or hospitalization. An AESI can be serious, but does not have to be. Conversely, not every SAE is an AESI. The AESI category describes the special professional interest and the pre-planned handling; the SAE category describes the severity of a specific event. Both categories can coincide in a case, but fulfill different purposes.
A signal, on the other hand, arises from information or a bundle of information suggesting a possible association between an intervention and an event and justifying a review. A signal is detected from data and validated; an AESI is defined even before data collection. An AESI analysis can support a signal, but does not automatically confirm a causal relationship. Signal management according to GVP Module IX requires a separate professional review of the available evidence.
The prioritized review serves the analysis, not a prejudgment of the medicinal product.
Relevance for clinical trials
AESIs make safety monitoring targeted, without replacing the general collection of adverse events. In practice, it is particularly important that study centers know the definitions and do not overlook additional examinations. Inconsistent terminology, missing baseline values or incomplete follow-up can significantly complicate the evaluation. The prospective planning also supports the appropriate information of participants and the decision on whether safety measures need to be adjusted during the course of the study.
Full-service CROs such as Mediconomics support the elaboration of AESI definitions in the protocol and safety management plan, the training of study centers and the follow-up of defined data points. Further services are medical coding, data reconciliation between data management and pharmacovigilance, the preparation of aggregated overviews and the support of safety reports. As a result, the special observation of an AESI and the regular processes for AEs, SAEs and SUSARs remain consistently connected.
Frequently Asked Questions (FAQ)
Is an AESI always a serious adverse event?
No. An AESI can also be non-serious. It is specifically collected and evaluated because of its pre-defined safety interest.
Is an AESI automatically assessed as an adverse reaction?
No. Causality is assessed for each case. The AESI classification merely means that a special and pre-planned observation is required.
Can an AESI become a signal?
Yes. An accumulation or a conspicuous pattern in an AESI can be the reason for a signal review. The signal status, however, requires a separate evaluation of the evidence.
Regulatory references
- ICH E6(R3) “Good Clinical Practice” – requires a risk-based, protocol-supported handling of safety data.
- ICH E2A “Clinical Safety Data Management” – defines the basic terms for adverse events and adverse reactions.
- Regulation (EU) No 536/2014 – regulates safety records and safety reporting in clinical trials.
- EMA GVP Module IX “Signal Management” – describes definition, validation and evaluation of signals.