Safety Reporting and Adverse Event Management
Safety is where terminology precision decides the answer. Sort the concepts: an adverse event is any untoward medical occurrence, whether or not related to the investigational product. A serious adverse event meets at least one criterion: death, life-threatening, inpatient hospitalisation or prolongation, persistent or significant disability, congenital anomaly, or an important medical event requiring intervention to prevent one of these.
Three independent axes
- Seriousness - a regulatory/medical definition. Severity (mild/moderate/severe) is a separate intensity scale; severe headache is usually not serious, and a mild but hospitalising event is.
- Causality - investigator-assessed relationship (related, possibly related, unrelated, or a similar scale). The sponsor cannot downgrade the investigator's assessment.
- Expectedness - judged against the investigator's brochure (or package insert) at the observed specificity and severity.
Serious + unexpected + suspected adverse reaction = SUSAR, which drives expedited reporting: generally 15 calendar days for IND safety reports, and 7 calendar days for unexpected fatal or life-threatening suspected reactions, with follow-up. Sites typically report SAEs to the sponsor within 24 hours per protocol; IRB timelines follow local policy. Separately, an unanticipated problem involving risk to subjects must be reported to the IRB. Pregnancies, overdose, and device malfunctions are handled per protocol even when no AE exists.
Traps
- Starting the clock when the PI reviews the case rather than when any site staff first learns of it.
- Coding symptoms instead of the unifying diagnosis.
- Reporting a planned hospitalisation for a pre-existing condition as an SAE.
- Assuming "unexpected" means never seen before; it means not described in the reference safety information.
Worked example: a subject is admitted for angioedema listed in the IB as "hypersensitivity, uncommon." Serious and related, but expected - not a SUSAR.