Dechallenge refers to the observation of what happens to an adverse event when the suspected causative drug is withdrawn or its dose reduced. A positive dechallenge occurs when the adverse event resolves or substantially improves following drug discontinuation, providing evidence supporting a causal relationship. A negative dechallenge, where the event persists despite drug withdrawal, suggests that other factors may be responsible, though it does not definitively exclude drug causality, particularly for reactions with long recovery times or irreversible effects.

The interpretation of dechallenge results requires consideration of the expected time course for resolution of the specific adverse event. Events that typically resolve rapidly, such as drug-induced nausea or headache, should show improvement within a timeframe consistent with drug elimination and pharmacological reversal. Events involving tissue damage, such as hepatotoxicity or nephropathy, may require extended observation periods to assess recovery. Some drug-induced effects may be irreversible, in which case negative dechallenge does not argue against causality.

Dechallenge is a routine component of adverse event management in clinical trials, as investigators typically discontinue or reduce the suspected drug when adverse events occur. Documentation of dechallenge outcomes is therefore frequently available for causality assessment. The protocol should provide guidance on whether and how to perform dechallenge, including whether dose reduction or complete discontinuation is preferred, the observation period for assessing response, and whether and under what circumstances rechallenge might be considered following successful dechallenge.