AE vs. AR — Fundamental Distinction
Adverse Event (AE)
Definition: Any untoward medical occurrence — no causal relationship required
Causality: Temporal association only
Scope: Broader — includes all events during exposure
Example: Patient taking Drug X falls and breaks an arm
vs.
Adverse Reaction (AR)
Definition: A noxious, unintended response — causal relationship suspected
Causality: At least a reasonable possibility of a link
Scope: Narrower — only events with suspected causality
Example: Patient taking Drug X develops hepatotoxicity
Classification Hierarchy
Hover over each box for details
AE
Adverse Event
Any untoward medical occurrence
No causality required. Includes any unfavorable medical event temporally associated with drug use, whether or not it is related to the treatment.
AR
Adverse Reaction
Causal relationship suspected
A noxious and unintended response to a medicinal product. Requires at least a reasonable possibility that the drug caused the event.
SAE
Serious Adverse Event
Meets seriousness criteria
Any AE that results in death, is life-threatening, requires hospitalization, causes persistent disability, congenital anomaly, or is an important medical event.
SAR
Serious Adverse Reaction
Serious + causally related
An adverse reaction that is also serious — meeting one or more of the ICH seriousness criteria while having a suspected causal link to the drug.
SUSAR
Suspected Unexpected SAR
Not in reference safety info
A serious adverse reaction that is also unexpected — its nature, severity, or specificity is not consistent with the applicable Reference Safety Information (IB for trials, SmPC/CCSI post-market).
Seriousness Criteria (ICH E2A)
Death
Any event resulting in the demise of the patient
Life-Threatening
Patient at immediate risk of death at the time of the event
Inpatient Hospitalization
Requiring admission of ≥24 hours or prolongation of existing stay
Persistent Disability
Substantial disruption of normal life functions
Congenital Anomaly
Birth defect in offspring of a patient exposed to the drug
Important Medical Event
May jeopardize the patient or require intervention — requires professional judgment
Clinical Insight — Important Medical Events
A seizure treated in an emergency room without hospital admission technically does not meet the hospitalization criterion, but professional judgment should classify it as serious under the IME category to prevent under-reporting of significant risks.
MedDRA Hierarchy
Five-level coding structure — hover for examples
Most general
SOC — System Organ Class
e.g., Cardiac Disorders
HLGT — High Level Group Term
e.g., Coronary Artery Disorders
HLT — High Level Term
e.g., Ischaemic Coronary Artery Disorders
Analysis level
PT — Preferred Term
e.g., Myocardial Infarction
Most specific
LLT — Lowest Level Term
e.g., Heart attack
Why Coding Matters for Signal Detection
If different coders use different terms for the same medical concept (e.g., "heart attack" vs. "myocardial infarction"), the statistical signal will be diluted across multiple Preferred Terms, potentially masking a genuine safety concern. Consistent MedDRA coding is the foundation of effective signal detection.