A clinical event, including laboratory test abnormality, occurring in a plausible time relationship to drug administration, and which cannot be explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the drug (de-challenge) should be clinically plausible. The event must be definitive pharmacologically or phenomenologically, using a satisfactory re-challenge procedure if necessary.
Probable / Likely
A clinical event, including laboratory test abnormality, with a reasonable time sequence to administration of the drug, unlikely to be attributed to concurrent disease or other drugs or chemicals, and which follows a clinically reasonable response on withdrawal (de-challenge). Re-challenge information is not required to fulfil this definition.
A clinical event, including laboratory test abnormality, with a reasonable time sequence to administration of the drug, but which could also be explained by concurrent disease or other drugs or chemicals. Information on drug withdrawal may be lacking or unclear.
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.
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 are under examination.
Un-assessable / Unclassifiable
A report suggesting an adverse reaction, which cannot be judged because information is insufficient or contradictory, and which cannot be supplemented or verified.
Various causality terms are in use but the following are used most widely. Some, however, do not use all the terms, for instance many do not believe that a ‘certain’ classification is possible for a single report and other make no distinction between ‘probable’ and ‘possible’. These definitions are however acceptable to Programme members who do use the terms. Where only ‘possible’ or ‘unlikely’ are used to describe reactions it must be understood that ‘possible’ include those reactions which are called by others ‘probable’ and ‘certain’, as well as ‘possible’.
Whilst ‘conditional / unclassified’ and ‘unassessable / unclassifiable’ are not causality terms, they describe the status of adverse reaction reports and therefore allow for practical communication about ADR issues.
Frequency of adverse drug reactions
Whenever possible, an estimate of frequency should be provided, expressed in standard category of frequency.
It is always difficult to estimate incidence on the basis of spontaneous reports, owing to the uncertainty inherent in estimating the denominator and degree of under-reporting. However, whenever possible, an estimate of frequency should be provided and in a standard form.
The following standard categories of frequency are recommended:
|Very common||> 1/10||(> 10%)|
|Common (frequent)||> 1/100 and < 1/10||(> 1% and < 10%)|
|Uncommon (infrequent)||> 1/1,000 and < 1/100||(> 0.1% and < 1 %)|
|Rare||> 1/10,000 and < 1,000||(> 0.01% and < 0.1%)|
|Very rare||< 1/10,000||(< 0.01%)|