PV Modules

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:

• Physician
• Medical Safety Officer
• Pharmacovigilance Scientist

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