MODULE 3: SERIOUSNESS ASSESSMENT

Seriousness assessment is a key step in the PV workflow to determine whether the adverse event (AE) requires expedited reporting to regulatory authorities.
It is performed during Case Validation after confirming the minimum criteria for an ICSR.

What is Seriousness?

Seriousness refers to the regulatory definition of how severe an AE is based on clear, internationally accepted criteria.

It is NOT the same as severity.

  • Severity = clinical intensity (mild/moderate/severe)
  • Seriousness = regulatory impact

Example:

  • Severe headache → severe but not serious
  • Mild anaphylaxis managed at home → mild but serious

ICH E2A SERIOUSNESS CRITERIA

An AE is considered SERIOUS if it meets any of the following 6 criteria:

1. Death

The patient dies as a result of the AE.

Examples:

  • Death due to anaphylaxis
  • Sudden cardiac arrest after drug intake

2. Life-threatening

The patient was at immediate risk of death at the time of the event.

Examples:

  • Severe hypotension
  • Severe anaphylaxis needing resuscitation
  • Ventricular arrhythmia

3. Hospitalisation (Initial or Prolonged)

Hospitalization due to the AE or AE leads to extension of existing stay.

Include:

  • Emergency admission
  • 24-hour observation admission

Exclude:

  • Elective/planned hospitalisation

Examples:

  • Drug-induced acute pancreatitis
  • GI bleed requiring admission

4. Disability or Permanent Damage

AE results in lasting physical, psychological, or functional impairment.

Examples:

  • Drug-induced hearing loss
  • Vision impairment
  • Permanent motor weakness

5. Congenital Anomaly/Birth Defect

Exposure to drug during pregnancy results in fetal abnormality.

Examples:

  • Antiepileptic drug → cleft palate in new-born
  • Isotretinoin exposure → birth defects

6. Required Intervention to Prevent Permanent Impairment

A medical or surgical intervention was needed to avoid permanent harm.

Examples:

  • Epinephrine administered to prevent respiratory collapse
  • Emergency antidote administration
  • Surgery to prevent organ damage

Non-Serious Adverse Events

These do NOT meet ICH seriousness criteria.

Examples:

  • Mild rash
  • Headache
  • Local injection site pain
  • Transient dizziness

Non-serious AEs go into periodic safety reporting:

  • PSUR (Periodic Safety Update Report)
  • PBRER (Periodic Benefit-Risk Evaluation Report)

SERIOUSNESS VS. SEVERITY – IMPORTANT DISTINCTION

Severity

Seriousness

Clinical intensity

Regulatory significance

Mild/Moderate/Severe

Serious / Non-serious

“Severe” does NOT mean serious

“Serious” does NOT mean severe

Example:

  • Severe vomiting → Not serious
  • Mild anaphylaxis at home → Serious (life-threatening)

EXPEDITED REPORTING TIMELINES (ICH E2A)

If a case is serious → must be reported rapidly to health authorities.

Fatal / Life-threatening

  • 7 Calendar Days

Other Serious Unexpected Cases

  • 15 Calendar Days

Examples of 7-day reporting cases:

  • Drug-induced cardiac arrest
  • Severe anaphylaxis
  • Fulminant hepatic failure

Examples of 15-day reporting cases:

  • Drug-induced pancreatitis
  • Seizures
  • Hospitalisation due to acute kidney injury

 NON-SERIOUS CASE REPORTING

Non-serious cases are not expedited.

They are included in:

  • PSUR (Periodic Safety Update Report)
  • PBRER (Periodic Benefit–Risk Evaluation Report)

Usually cumulative data, submitted every:

  • 6 months
  • 1 year
  • 3 years (depending on regulatory phase)

EXAMPLES

Example 1

A 40-year-old male hospitalized for drug-induced pneumonia.

·         Serious — Hospitalisation

·         15-day report

Example 2

A patient died after a dose of chemotherapy.

·         Serious — Death

·         7-day report

Example 3

Mild vomiting after taking antibiotic.
✘ Not Serious
→ Periodic reporting only

Example 4

Pregnant woman took Drug X, delivered baby with limb deformity.

·         Serious — Congenital anomaly

·         Expedited reporting (15 days)

Example 5

Patient fainted but recovered at home, no medical visit.
Decision: Was the fainting life-threatening?
If yes → Serious
If no → Non-serious

Medical confirmation needed based on description.

RED FLAGS THAT INDICATE SERIOUSNESS

  • ICU admission
  • Emergency surgical intervention
  • Organ failure
  • Seizures
  • Loss of consciousness
  • Severe bleeding
  • Stroke-like symptoms
  • Foetal exposure with abnormal ultrasound

How PSAs Document Seriousness

A PSA must:

·         Select the seriousness criterion

·          Capture the date of outcome

·         Document clinical details clearly

·         Justify the seriousness choice

·         Determine expedited timeline

Route the case for rapid submission.