SafetyGlossary Term
ICH E2A Section II.B
The discontinuation or dose reduction of a suspected drug following an adverse event to observe whether the event resolves or improves, providing evidence about the causal relationship.
Dechallenge refers to the observation of what happens to an adverse event when the suspected causative drug is withdrawn or its dose reduced.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.
Positive dechallenge
"Following discontinuation of the study drug due to persistent nausea and vomiting, the participant's symptoms resolved completely within 72 hours, representing a positive dechallenge that supported a causal relationship with the investigational product."
Inconclusive dechallenge
"Although the drug was discontinued immediately upon diagnosis of peripheral neuropathy, the symptoms persisted for several months due to the known slow recovery from nerve damage, making the dechallenge uninformative for causality assessment."
A response to a medicinal product that is noxious and unintended, where a causal relationship between the product and the adverse event is at least a reasonable possibility.
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product.
The strictest warning required by the FDA to appear on prescription drug labeling, alerting prescribers and patients to serious risks that may lead to death or severe injury.
The systematic evaluation of the likelihood that an adverse event was caused by the investigational product or another factor, using established criteria to determine the relationship between exposure and outcome.
A standardized one-page format developed by the Council for International Organizations of Medical Sciences for reporting suspected adverse drug reactions from clinical trials to regulatory authorities.
ICH E2A Section II.B
The discontinuation or dose reduction of a suspected drug following an adverse event to observe whether the event resolves or improves, providing evidence about the causal relationship.
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.
Positive dechallenge
"Following discontinuation of the study drug due to persistent nausea and vomiting, the participant's symptoms resolved completely within 72 hours, representing a positive dechallenge that supported a causal relationship with the investigational product."
Inconclusive dechallenge
"Although the drug was discontinued immediately upon diagnosis of peripheral neuropathy, the symptoms persisted for several months due to the known slow recovery from nerve damage, making the dechallenge uninformative for causality assessment."
A response to a medicinal product that is noxious and unintended, where a causal relationship between the product and the adverse event is at least a reasonable possibility.
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product.
The strictest warning required by the FDA to appear on prescription drug labeling, alerting prescribers and patients to serious risks that may lead to death or severe injury.
The systematic evaluation of the likelihood that an adverse event was caused by the investigational product or another factor, using established criteria to determine the relationship between exposure and outcome.
A standardized one-page format developed by the Council for International Organizations of Medical Sciences for reporting suspected adverse drug reactions from clinical trials to regulatory authorities.