MODULE 9: MEDICAL REVIEW

Medical Review is the clinical evaluation of an adverse event (AE) case before it is submitted to regulatory authorities. It ensures that the case is scientifically accurate, medically sound, and compliant with regulations.

Who Performs Medical Review?

Medical Review is conducted by qualified medical and safety professionals, typically:

• Physician / Medical Doctor (MD)

  • Provides expert clinical judgement
  • Evaluates the logical medical relationship between drug and event

• Medical Safety Officer (MSO)

  • Ensures the case aligns with company safety strategy
  • Identifies potential signals or trends

• Pharmacovigilance Scientist / Safety Reviewer

  • Performs medical analysis along with data accuracy checks
  • Supports physician with evidence and documentation

2. Key Elements Reviewed During Medical Review

The medical reviewer thoroughly evaluates various scientific and regulatory components of the case:

A. Coding Accuracy

  • Ensures MedDRA terms (PT, LLT) are correctly selected
  • Ensures WHO-DD coding is correct for drug names/indications
  • Verifies that coding represents the true clinical situation

Example:
“Swelling of lips” should be coded as “Lip swelling” (PT), not “Angioedema” unless clinically diagnosed.

B. Causality Assessment

The medical reviewer determines whether the drug likely caused the AE.

Common causality tools:

  • WHO-UMC scale
  • Naranjo’s scale
  • Company-specific causality criteria

They consider:

  • Temporal relationship
  • Dechallenge/rechallenge
  • Biological plausibility
  • Known side effect profile
  • Concomitant medications
  • Underlying disease

C. Expectedness Assessment

Reviewer determines whether the AE is:

  • Expected (listed in Product Information / Investigator Brochure)
  • Unexpected (not listed → potential SUSAR in clinical trials)

Expectedness determines:

·         Expedited reporting timelines

·         Whether the event qualifies as a SUSAR

D. Narrative Quality

The reviewer ensures the narrative is:

  • Clear
  • Chronological
  • Complete
  • Clinically meaningful
  • Free of speculation
  • Contains all details on AE onset, drug history, relevant tests, outcomes, etc.

A good narrative must allow a regulator to understand the full medical picture without reading other sections.

E. Seriousness Classification

The reviewer checks whether seriousness is correctly assigned based on ICH criteria:

  • Death
  • Life-threatening
  • Hospitalisation
  • Disability
  • Congenital anomaly
  • Medically important condition

Incorrect seriousness can lead to incorrect reporting timelines, so accuracy is crucial.

F. Completeness Check

Ensures all minimum and essential data are present:

Minimum 4 criteria:

  1. Identifiable patient
  2. Identifiable reporter
  3. Suspect drug
  4. Adverse event

Additional essential data:

  • Lab results
  • Relevant medical history
  • Treatment details
  • Lot/batch numbers (if required)
  • Concomitant medications

Reviewer may request follow-up information before sign-off.

3. Output of Medical Review

After review, the medical reviewer:

·         Confirms medical accuracy

·         Signs off (electronically in the safety database)

·         Approves case for regulatory submission

Medical review sign-off is mandatory for:

  • ICSR Regulatory Submission (VAERS, EudraVigilance, FDA)
  • SUSAR reporting in clinical trials
  • Aggregate reports (DSUR, PBRER)

4. Importance of Medical Review

Medical Review ensures:

  • Clinical validity
  • Regulatory compliance
  • Prevention of misreporting
  • Swift identification of safety signals
  • Patient safety protection

It is the final gate before a case leaves the company.

5. Example Case for Medical Review

Case:
A 54-year-old male taking Drug X developed “high fever and rash” on Day 3.
He visited a hospital and received treatment.
Drug withdrawn → patient improved (positive dechallenge).

Medical Reviewer conclusions:

  • AE coding:
    PT: “Drug eruption”
  • Seriousness: Hospitalisation = Serious
  • Causality: Probable
  • Expectedness: Unexpected (not listed in SmPC)
  • Reporting: 15-day expedited report
  • Narrative: Must include timeline and dechallenge