The document “The use of the WHO-UMC system for standardised case causality assessment” provides a detailed explanation of the WHO-UMC causality assessment system, which is used in pharmacovigilance to evaluate the likelihood that a suspected adverse drug reaction (ADR) is actually caused by a drug.
Here’s a detailed breakdown of the content:
1. Why Causality Assessment?
- In pharmacovigilance, most ADR reports are suspected, not confirmed.
- ADRs are rarely certain; they often fall between “certain” and “unlikely”, typically categorized as “possible” or “probable”.
- Causality assessment helps:
- Reduce disagreement between assessors
- Classify the likelihood of a drug-event relationship
- Improve scientific evaluation and education
- However, it cannot:
- Provide precise quantitative likelihood
- Distinguish valid from invalid cases
- Prove a causal link
- Turn uncertainty into certainty
2. The WHO-UMC System
- Developed with input from National Centres in the WHO Programme for International Drug Monitoring.
- Focuses on clinical-pharmacological aspects and quality of documentation.
- Less emphasis on prior knowledge or statistical chance.
- Designed to be practical, unlike more complex or specific algorithms.
3. Causality Categories
The system defines six causality categories, each with specific criteria:
| Category | Key Criteria |
|---|---|
| Certain | – Plausible time relationship – Cannot be explained by disease/other drugs – Positive response to withdrawal – Event is pharmacologically/phenomenologically definitive – Rechallenge satisfactory (if done) |
| Probable/Likely | – Reasonable time relationship – Unlikely due to disease/other drugs – Clinically reasonable response to withdrawal – Rechallenge not required |
| Possible | – Reasonable time relationship – Could be explained by disease/other drugs – Withdrawal information may be lacking/unclear |
| Unlikely | – Time relationship makes causality improbable – Other causes provide plausible explanation |
| Conditional/Unclassified | – More data needed for assessment – Data under examination |
| Unassessable/Unclassifiable | – Insufficient or contradictory information – Cannot be supplemented or verified |
4. Key Distinctions Between Categories
- Certain vs. Probable:
- Certain requires the event to be definitive (e.g., anaphylaxis, grey baby syndrome) and a plausible time relationship.
- Probable requires only a reasonable time relationship and does not require rechallenge.
- Probable vs. Possible:
- In Possible, other causes are equally likely, or withdrawal information is unclear.
- Unlikely is used when the time relationship is improbable or other causes are more plausible.
5. How to Use the System
- Most cases fall into Possible or Probable.
- Start with one of these and adjust based on evidence:
- If evidence is stronger → move to a higher category (e.g., Possible → Probable)
- If weaker → move to a lower category
- For drug-drug interactions, assess the actor drug that influences the other drug’s kinetics or dynamics.
6. Conclusion
- The WHO-UMC system is a practical, standardized tool for causality assessment in pharmacovigilance.
- It emphasizes clinical and pharmacological reasoning over statistical or prior knowledge.
- The system is educational and improves consistency, though it does not eliminate uncertainty.
