MODULE 4: CASE PROCESSING

Case Processing is the core operational activity of Pharmacovigilance.
Once a case is validated (minimum 4 criteria confirmed), it moves into processing, where the PSA enters, evaluates, codes, and prepares the case for medical and quality review.

Objectives of Case Processing

  • To accurately and completely capture adverse event information in the safety database
  • To ensure medical accuracy and consistency
  • To prepare the case for expedited or periodic regulatory reporting
  • To maintain data integrity for signal detection and risk assessment

Steps in Case Processing

Case processing typically includes the following components:

Step 1: Data Entry in Safety Database

Once a case is validated, it is entered into a safety database like:

  • Argus
  • ArisG
  • Veeva Vault Safety
  • MedDRA-supported systems

The PSA enters details in structured fields:

Data entered includes:

·         Patient demographics

·         Suspect & concomitant medications

·         Adverse event details

·         Lab reports / investigations

·         Reporter details

·         Past medical history

·         Treatment details

·         Product information

·         Reporter’s narrative

Key Principle:

“Enter exactly what the reporter says—no assumptions, no editing.”

Step 2: Chronology & Timeline Building

The PSA reconstructs the sequence of events:

  1. Drug start date
  2. Event onset date
  3. Hospitalization dates
  4. Outcome date
  5. Date of last dose
  6. Recovery or follow-up dates

Why it matters:

  • Helps assess causality
  • Determines expectedness
  • Supports regulatory timelines

Step 3: Medical Coding (Standardization)

Terminologies must be standardized to support global consistency.

(A) MedDRA Coding for Adverse Events

Using MedDRA hierarchy:

  • LLT (Lowest Level Term)
  • PT (Preferred Term)
  • HLT
  • SOC

Example:
“Severe stomach pain” → LLT (Abdominal pain) → PT: Abdominal Pain

Rules:

·         Code what is reported

·         Avoid interpreting or diagnosing

·         Do not code severity or seriousness

(B) WHO-DD Coding for Drugs

Used for:

  • Suspect drugs
  • Concomitant medications
  • Indications

Ensures standardized drug names.

Step 4: Causality Assessment

Determines whether drug caused the event.

Most common tools:

  • WHO-UMC causality scale
  • Naranjo algorithm
  • Manufacturer’s internal guidance
  • Clinical judgment by medical reviewer

Categories:

  • Certain
  • Probable
  • Possible
  • Unlikely
  • Unassessable

Factors assessed:

·         Temporal relationship

·         Dechallenge / Rechallenge

·         Known pharmacology

·         Alternative causes

·         Drug-drug interactions

Step 5: Expectedness Assessment

Determines whether the AE is mentioned in:

  • Investigator’s Brochure (IB) — Clinical trials
  • Company Core Data Sheet (CCDS) — Post-marketing
  • Product Label / SmPC / PI

Classification:

  • Expected (Listed)
  • Unexpected (Unlisted)

Use:

  • Determines 15-day reporting for Serious Unexpected cases

Step 6: Narrative Writing

The narrative is the complete medical story of the case.

Should include:

·         Patient details

·         Drug details (suspect and concomitant)

·         Full chronology

·         AE details

·         Seriousness criteria

·         Relevant medical history

·         Lab reports

·         Reporter’s statements

·         Treatment given

·         Outcome

Golden rule:

Clear, concise, chronological, medically accurate.

Step 7: Follow-up Request (If Needed)

Follow-up needed when:

  • Missing minimum criteria
  • Missing dates
  • Incomplete drug information
  • Seriousness unclear
  • Outcome missing
  • Pregnancy cases
  • Lack of essential labs

Requests are sent via:

  • Email
  • Call
  • Safety query letters
  • Medical information teams

Step 8: Medical Review

Performed by:

They review:

·         Coding accuracy

·         Causality

·         Expectedness

·         Narrative quality

·         Seriousness classification

·         Completeness

Their sign-off is necessary for regulatory submission.

Step 9: Quality Review (QA Check)

QA ensures:

  • Accuracy
  • Consistency
  • Alignment with SOPs & regulatory guidelines
  • Formatting correctness

Audit trail must be maintained.

Step 10: Regulatory Submission

Based on seriousness & expectedness:

Serious Unexpected → 15-Day Report

Fatal/Life-threatening → 7-Day Report

Non-serious → PSUR/PBRER

Cases are transmitted via:

  • E2B (R2 or R3) XML
  • Gateway submission
  • National portals (FDA, EMA, MHRA, PVPI etc.)

Case Processing Workflow

Intake → Validation → Data Entry → Coding → Causality → Expectedness → Narrative → QA → Medical Review → Submission

Important Tips for PSAs

  • Never assume missing information
  • Use exact reporter words
  • Always check chronology
  • Run consistency checks
  • Ensure seriousness criteria match narrative
  • Validate MedDRA codes carefully
  • Maintain clean, professional narrative style

Example of Case Processing

Reporter says:
“Patient took Amoxicillin for 3 days and developed rash and fever. Stopped drug on Day 4. Rash improved.”

What the PSA does:

✔ Validate case → Yes (all 4 criteria present)
✔ Enter demographics
✔ Enter suspect drug + start/stop dates
✔ Enter AE onset date
✔ MedDRA code “Rash” and “Pyrexia”
✔ Assess seriousness → Non-serious
✔ Causality → Probable (temporal relation + dechallenge)
✔ Expectedness → Expected
✔ Write narrative
✔ Send for QA and Medical review
✔ Submit case as part of periodic reporting