The causal relationship between an AE and a suspected drug can be, according to the WHO:
- certain– sufficient information provided to determine that no other reasonable explanation exists, occurring in a plausible time relationship to drug administration, and which cannot be explained by concurrent disease or other drugs or chemicals.
- (A) probable, likely – sufficient information provided to no other equally plausible explanation exists,
- (B) possible – information provided supports a reasonable time sequence to administrations of the drug, but which could also be explained by another equally possible explanation (i.e. concurrent disease or other drugs or chemicals). Information on drug withdrawal may be lacking or unclear.
- (O1) conditional, unclassified – a clinical event, including laboratory test abnormality, reported as an adverse reaction, about which more data is essential for a proper assessment, or the additional data is under examination.
- (O) unassessable, unclassifiable – a report suggesting an adverse reaction which cannot be judged because information is insufficient or contradictory, and which cannot be supplemented or verified.
- (N) unlikely – a clinical event, including laboratory test abnormality, with a temporal relationship to drug administration which makes a causal relationship improbable, and in which other drugs, chemicals or underlying disease provide plausible explanations
It is determined based on:
- Temporal relationship, drug’s half-life
- Pathological mechanisms
- Alternative explanations for the event
- Dechallenge and rechallenge
- Concomitant diseases or use of other medicines
- Previous experience with the drug…
