Bioequivalence and Bioavailability Forum

Dear ssk!

❝ Can anyone explain how to classify the adverse events as possible, probable, certain, remote.

Almost every CRO has a different SOP for coding AEs (never heard about 'remote'). Some examples I came across follow:
(1) not related, (2) unlike, (3) possible, (4) probable, (5) definite, (6) not assessable
(1) definite, (2) probable, (3) possible, (4) unlikely, (5) impossible to determine
(1) certain, (2) probable, (3) possible, (4) unlikely, (5) conditional, (6) inestimable
(1) suspected, (2) not suspected, (3) unassessable

Example of a detailed rating:

Category ‘A’

• A reaction that follows a reasonable temporal sequence from administration of the drug, that follows a known or expected response pattern to the suspected drug; that is confirmed by improvement on stopping or reducing the dosage of the drug, and reapparance of the reaction on repeated exposure (connection to study drug is certain: 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 clinically be plausible. The reaction must be definitive pharmacological or phenomenological, using a satisfactory re-challenge procedure if necessary).
  
• A reaction that follows a reasonable temporal sequence from administration of the drug; that follows a known or expected response pattern to the suspected drug, that is confirmed by improvement on stopping or reducing the dosage of the drug and that could not be reasonably explained by the known characteristics of the volunteer's clinical state (connection to study drug is 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).

Category ‘B’

• A reaction that follows a reasonable temporal sequence from administration of the drug, that follows a known or expected response pattern to the suspected drug but that could readily have been produced by a number of other factors (connection to study drug is possible: 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 reaction that follows a reasonable temporal sequence from administration of the drug, that follows a known or expected response pattern to the suspected drug but that could reasonably be explained by known characteristics of the volunteers clinical state (connection to study drug is 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 explanation).

Category ‘O’

• Any reaction that does not meet the above criteria; there is sufficient information that the aetiology of the reaction is not connected with the study drug (no connection with study drug 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).
  
• A judgment of the relation to study drug is not possible. The statements that are available will not suffice for a definite judgment (connection with study drug not possible to judge unassessable/unclassified: A report suggesting an adverse reaction which cannot be judged because information is insufficient or contradictory, and which cannot be supplemented or verified).

Also have a look at the WHO-UMC classification system.

Whatever rating system you adopt, it has to follow the Investigator’s Brochure (and should be stated in the protocol/CRF as well).
If you are dealing with a new drug, it will not make sense to include a rating ‘definite/certain’, because we simply don’t know yet!