SUSAR (Suspected Unexpected Serious Adverse Reaction)

A SUSAR (Suspected Unexpected Serious Adverse Reaction) is an adverse event in a clinical trial that is simultaneously serious, suspected to be caused by the investigational product, and unexpected given what is already documented about the product’s safety profile. The term comes from ICH E2A, “Clinical Safety Data Management: Definitions and Standards for Expedited Reporting” (finalized 1994), and it is the specific classification that triggers expedited, case-by-case safety reporting to regulators — as opposed to the routine, aggregated adverse-event data collected throughout a trial and reported periodically.

The three-part SUSAR test

An event only qualifies as a SUSAR if all three of the following are true at once:

• Serious. The event meets one of the ICH E2A seriousness criteria: it results in death, is life-threatening, requires or prolongs hospitalization, causes persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is another medically important event that the investigator judges serious based on clinical judgment. See Serious Adverse Event (SAE) for the full breakdown of these criteria.
• Suspected. The investigator or sponsor assesses there is a reasonable possibility the investigational product caused the event — this is a lower bar than proven causation, but higher than mere temporal coincidence.
• Unexpected. The event’s nature, severity, or specificity is not consistent with the reference safety information in the current edition of the Investigator’s Brochure, or, for an approved product used as a comparator, the approved labeling. An adverse reaction already described as a known risk is, by definition, expected — no matter how serious it is.

All three elements have to hold together. A serious, unexpected event judged unrelated to the drug is not a SUSAR. Neither is a serious, suspected-related event that is already a documented, expected risk of the product.

Why SUSARs get expedited reporting

Identifying an event as a SUSAR is what separates expedited, individual-case safety reporting from routine trial safety monitoring. In the US, sponsors holding an active IND must report SUSARs to FDA and to all participating investigators under 21 CFR 312.32: fatal or life-threatening SUSARs within 7 calendar days of the sponsor’s initial receipt of the information, with a complete follow-up report within an additional 8 days, and all other SUSARs within 15 calendar days. See IND Safety Report for the mechanics of that specific filing. In the EU, sponsors report SUSARs on the same 7-/15-day structure to the EudraVigilance database under Regulation (EU) No 536/2014, reflecting the same underlying ICH E2A definitions harmonized internationally. This is distinct from routine adverse-event data, which is collected continuously across a trial and reported in aggregate through periodic mechanisms such as annual IND reports or a Development Safety Update Report (DSUR), rather than case by case as it happens. For the fuller picture of how AE, SAE, and SUSAR reporting fit together across a trial, see Pharmacovigilance in Clinical Research: AE, SAE, and SUSAR Reporting.

SUSAR vs. related terms

A SUSAR is a subset of a Serious Adverse Event (SAE), which is itself a subset of any Adverse Event (AE). Not every SAE is a SUSAR — an SAE only becomes a SUSAR when causality is suspected and the event is unexpected. A related but distinct category is the Adverse Event of Special Interest (AESI), which a protocol may flag for close monitoring regardless of seriousness or expectedness. Good Clinical Practice expectations for identifying and assessing these events are set out in ICH E6(R2).