Adverse Events of Special Interest is an important concept in management of safety risks for medicinal products and vaccines.
The is no single definition of AESIs but there are a couple of regulatory documents that defines the concept.
CIOMS IV guidance defines an AESI already back in 1998 as a serious or non-serious scientific or medical concern specific to the sponsor’s product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor could be appropriate.
Such an event may require investigation to further characterize and understand these types of events.
Other parties (e.g. regulators, health authorities) may need or wish to learn about such events quickly, depending on the nature of the event.
The CIOMS guidance was, as it often happens, used as foundation for the ICH E2F document completed in 2010 which is implemented in law in all 3 ICH regions (US, EU and Japan) and later in many other jurisdictions.
ICH E2F defines how a Development Safety Update Report (DSUR) should be composed as as part of the DSUR structure there is a requirement to include AESIs:
- “If important and appropriate, the report should also include adverse reactions of special interest within the line listings and adverse events of interest in summary tabulations. The basis for selection of such events/reactions should be explained.”
If these are deemed important enough by us to collect as AESIs, they should be included within the DSUR. Some regulatory agencies or health authorities may ask for expedited reporting of these events, depending on the type of event.
AESIs may warrant collection across the entire study population to better characterise these events (e.g., particular laboratory parameters; vital signs; risk factors; concomitant therapies; and/or comitant illnesses). For example, if gastrointestinal haemorrhage was an adverse event of special interest,you might want to collect antithrombotic therapy proactively.
Reporting AESI is an important aspect related to characterising the safety profile of a medicinal product in clinical trials. It is important to define clearly “adverse events of special interest” in the protocol and to specify close monitoring and prompt reporting to the sponsor of these types of events, even if the event is non-serious according to the usual regulatory criteria.
These non-serious AESIs might be symptoms of more serious medical conditions; for example, muscle pain and elevated Creatine Phosphokinase (CPK) together may be symptoms of rhabdomyolysis.
In the early stages of development non-clinical research and toxicology may suggest the potential for important adverse events in humans and identification of such issues are very important prior to initiation of clinical trials.
Sponsor should identify adverse events of special interest from these data, or sometimes from experiences with similar compounds, that require special AESI collection and reporting by the investigator.
For example, if a compound in development has been demonstrated to have the ability to cause delayed conduction of electrical pulses in the heart in pre-clinical studies or if this is a concern with other compounds in the same class, it would be an indicator for particular caution in human trials. ECGs should therefore be monitored and arrhythmia routinely reported by investigators to sponsors for all subjects/patients until the risk to humans is clarified.
Templates for the most common 100 AESIs with relevant details to collect for each type of AESI are available here