AE / SAE / ADR

Adverse Event / Serious Adverse Event / Adverse Drug Reaction

The three terms are not interchangeable, and the differences drive legal reporting obligations. An adverse event is any untoward medical occurrence in a patient administered a medicinal product — it does not have to be caused by the product. An adverse drug reaction adds causality: a reasonable possibility that the product caused the event. Seriousness is a separate axis again, defined by outcome, not by how severe it felt.

ICH E2A defines serious by specific criteria: results in death, is life-threatening, requires or prolongs inpatient hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect. Important medical events that jeopardise the patient and may require intervention to prevent one of those outcomes are also handled as serious. Note that "severe" is not the same as "serious" — a severe headache may be non-serious; an asymptomatic but life-threatening arrhythmia is serious.

In clinical trials, the reportable subset is the SUSAR — a suspected unexpected serious adverse reaction, meaning serious, at least possibly related, and not consistent with the reference safety information. SUSAR clocks are short and start when the sponsor first becomes aware: 7 calendar days for fatal or life-threatening cases, 15 calendar days for other SUSARs.

• —AE — any untoward occurrence; causality not required.
• —ADR — an AE with at least a reasonable possibility of causal relationship.
• —Serious — defined by outcome (death, life-threatening, hospitalisation, disability/incapacity, congenital anomaly), not by intensity.
• —"Severe" ≠ "serious" — severity describes intensity, seriousness describes outcome.
• —SUSAR = serious + suspected related + unexpected against the reference safety information.
• —Expedited clocks: 7 calendar days (fatal/life-threatening), 15 calendar days (other SUSARs), from sponsor awareness.

ICH E2A (Clinical Safety Data Management: Definitions and Standards for Expedited Reporting); US: 21 CFR 312.32 (IND safety reporting) and 21 CFR 314.80 (postmarketing); EU: Regulation (EU) No 536/2014 for clinical trials and GVP Module VI for post-authorisation.