Seriousness & Causality Assessment

MAH's assessment of causal relationship between drug and event; uses criteria (e.g., WHO-UMC, Naranjo) and is documented in case file.

Criteria defining serious AE: death, life-threatening, hospitalization, disability, congenital anomaly, other medically important.

Event that may not be immediately life-threatening but may jeopardize the patient or require intervention to prevent one of the serious outcomes.

Re-administration of the drug followed by recurrence of the reaction; supports causality.

Improvement or resolution after drug withdrawal; supports causal association.

Clinically relevant interaction between drugs (or drug–food); may be in SmPC and affect causality or signal.

Birth defect or malformation; serious and reportable. Pregnancy follow-up aims to capture outcome including anomalies.

Case in which the patient died; always serious. Expedited reporting often shorter timeline (e.g., 7 days). Autopsy if available.

Seriousness criterion: event that placed the patient at immediate risk of death.

Seriousness: initial or prolonged hospitalization; includes admission for observation.

Seriousness: substantial disruption of ability to conduct normal life functions.

Time relationship between drug and event; key for causality (e.g., onset after start, improvement after stop).

Other plausible cause for the event (e.g., underlying disease, other drug); considered in causality.

Whether the drug–event association is consistent with known mechanism; supports or weakens causality.

The final status of an adverse event at the time of the last observation, categorized as recovered, recovering, not recovered, recovered with sequelae, fatal, or unknown.

A potential cause of an adverse event other than the suspect drug, such as underlying disease, concomitant medications, or environmental factors.

The extent to which a causal relationship between drug and event is consistent with known pharmacology, mechanism of action, or scientific evidence.

The systematic evaluation of the likelihood that a suspect drug caused or contributed to an adverse event, using clinical judgment and established algorithms.

The Marketing Authorization Holder's or sponsor's evaluation of causality, which may differ from the reporter's assessment but must be documented and justified.

A standardized grading scale (1-5) developed by NCI to describe the severity of adverse events, commonly used in oncology clinical trials.

A substantial disruption of the patient's ability to conduct normal life functions resulting from an adverse event, qualifying it as serious.

Whether an adverse event's nature and severity are consistent with the applicable reference safety information (product label, IB, or RSI).

Formal inpatient admission to a hospital for treatment or observation, which qualifies an adverse event as serious. Emergency room visits alone typically do not qualify unless followed by admission.

An adverse event that may not meet other seriousness criteria but requires medical judgment because it may jeopardize the patient or require intervention to prevent a serious outcome.

An adverse event that places the patient at immediate risk of death at the time of the event. This refers to the event's immediate impact, not its potential future consequences.

An adverse event that is described in the Reference Safety Information, meaning it is an expected or known risk of the medicinal product.

A probability scale using 10 weighted questions to estimate the likelihood of an adverse drug reaction, producing scores categorized as definite, probable, possible, or doubtful.

A causality assessment conclusion indicating a reasonable possibility that the drug caused or contributed to the adverse event, triggering reporting obligations.

An adverse event that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, results in persistent/significant disability, is a congenital anomaly, or is an important medical event.

The six regulatory criteria used to determine if an adverse event qualifies as serious: death, life-threatening, hospitalization, disability, congenital anomaly, or important medical event.

The intensity or grade of an adverse event (mild, moderate, severe, life-threatening, fatal), which is distinct from regulatory seriousness.

An adverse event whose nature, severity, specificity, or outcome is not consistent with the applicable reference safety information for the product.

A causality assessment conclusion indicating no reasonable possibility that the drug caused or contributed to the adverse event, typically due to clear alternative etiology or implausible timing.

A system developed by the WHO Uppsala Monitoring Centre using clinical judgment to classify causality as certain, probable/likely, possible, unlikely, conditional, or unassessable.