SafetyGlossary Term
ICH E2E Section II.A
Information from one or multiple sources that suggests a new potentially causal association, or a new aspect of a known association, between an intervention and an adverse event or set of related adverse events.
A safety signal represents information that raises a hypothesis about a potential risk associated with an investigational or marketed product, warranting further investigation to determine whether a true causal relationship exists. Signals may emerge from various sources, including disproportionate adverse event reporting in clinical trials, statistical patterns identified through data mining of safety databases, published case reports or epidemiological studies, or pharmacological considerations suggesting biological plausibility for an adverse effect.
Signal detection in clinical development involves both prospective and retrospective approaches. Prospective methods include prespecified safety monitoring plans that define thresholds for adverse event frequencies and stopping rules for unacceptable safety findings. Retrospective approaches analyze accumulating safety data using statistical techniques such as disproportionality analysis, which compares the observed frequency of drug-event combinations against expected frequencies. The Data Safety Monitoring Board plays a critical role in signal evaluation, providing independent expert assessment of emerging safety information.
Not every potential signal represents a true risk. Signal validation involves comprehensive evaluation to distinguish genuine safety concerns from statistical noise, confounding, or reporting artifacts. This evaluation considers factors such as the strength of the association, consistency across different data sources, temporal relationship, biological plausibility, and the quality of the underlying data. Validated signals proceed to signal prioritization and assessment, ultimately informing risk management decisions that may include protocol amendments, labeling changes, or in severe cases, trial termination or product withdrawal.
Signal detection
"Statistical analysis revealed that the incidence of thrombotic events in the treatment arm was 2.5 times higher than in the placebo arm, representing a potential safety signal that required immediate evaluation by the Data Safety Monitoring Board."
Signal validation
"The sponsor convened an ad hoc safety review committee to evaluate whether the apparent clustering of renal adverse events represented a true safety signal or was attributable to the high baseline prevalence of renal disease in the study population."
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 E2E Section II.A
Information from one or multiple sources that suggests a new potentially causal association, or a new aspect of a known association, between an intervention and an adverse event or set of related adverse events.
A safety signal represents information that raises a hypothesis about a potential risk associated with an investigational or marketed product, warranting further investigation to determine whether a true causal relationship exists. Signals may emerge from various sources, including disproportionate adverse event reporting in clinical trials, statistical patterns identified through data mining of safety databases, published case reports or epidemiological studies, or pharmacological considerations suggesting biological plausibility for an adverse effect.
Signal detection in clinical development involves both prospective and retrospective approaches. Prospective methods include prespecified safety monitoring plans that define thresholds for adverse event frequencies and stopping rules for unacceptable safety findings. Retrospective approaches analyze accumulating safety data using statistical techniques such as disproportionality analysis, which compares the observed frequency of drug-event combinations against expected frequencies. The Data Safety Monitoring Board plays a critical role in signal evaluation, providing independent expert assessment of emerging safety information.
Not every potential signal represents a true risk. Signal validation involves comprehensive evaluation to distinguish genuine safety concerns from statistical noise, confounding, or reporting artifacts. This evaluation considers factors such as the strength of the association, consistency across different data sources, temporal relationship, biological plausibility, and the quality of the underlying data. Validated signals proceed to signal prioritization and assessment, ultimately informing risk management decisions that may include protocol amendments, labeling changes, or in severe cases, trial termination or product withdrawal.
Signal detection
"Statistical analysis revealed that the incidence of thrombotic events in the treatment arm was 2.5 times higher than in the placebo arm, representing a potential safety signal that required immediate evaluation by the Data Safety Monitoring Board."
Signal validation
"The sponsor convened an ad hoc safety review committee to evaluate whether the apparent clustering of renal adverse events represented a true safety signal or was attributable to the high baseline prevalence of renal disease in the study population."
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.