GVP Module IX: Signal Management Knowledge Assessment

Validation automatically mandates a product-information change Validation automatically establishes causality and requires an RMP amendment Validation initiates further assessment; the eventual outcome may be action, monitoring, further data generation or documented no-action Validation has no consequences beyond recording the signal in a tracker

It cannot be a signal because the adverse reaction is already known It may constitute a signal concerning a new aspect of an existing association It is automatically a confirmed new risk It should be excluded because only completely unknown events qualify as signals

Ignore the concentration because stratification can introduce complexity Automatically classify the disease as a contraindication Investigate the population-specific context, including baseline risk and relevant clinical factors Replace the cases with reports from the general population

Disproportionality methods can only be used after a signal has been confirmed Statistical patterns may be influenced by reporting behaviour, exposure, co-medication or other factors and therefore require clinical evaluation Quantitative methods are prohibited under EU pharmacovigilance requirements A disproportionality alert is always less reliable than an isolated case report

The MAH may suspend its own assessment because the regulator has assumed responsibility The MAH remains responsible for an effective internal process and must manage the regulatory interface The MAH should alter internal records to match the regulatory conclusion retrospectively The MAH should consider only information formally requested by the regulator

It allows the organisation to avoid documenting a final rationale It preserves the ability to detect whether accumulating evidence changes the current conclusion It guarantees that the signal will eventually be confirmed It replaces the need to assign an owner or due date

Only spontaneous reports because other sources are not suitable for signal detection Only literature because published evidence has already undergone scientific review Relevant combinations of cases, literature, clinical data, studies, registries, epidemiology and other safety information Only regulatory communications because they represent confirmed safety risks

To identify every unusual reporting pattern and convert it into a regulatory action To convert relevant new safety information into a controlled process of scientific assessment and proportionate decision-making To replace individual case causality assessment with automated statistical analysis To ensure that all known adverse reactions are removed from the safety specification

It ensures that all closed signals are automatically reopened annually It allows later evidence to be interpreted in relation to the earlier assessment rather than treated as entirely unrelated It prevents regulators from reviewing the original conclusion It eliminates the need for continued monitoring

PSURs replace the need for signal management Signal conclusions and aggregate safety evaluations should inform one another in a controlled manner Only signals that result in regulatory action may be discussed in a PSUR PSUR authors should independently decide whether prior signal assessments were correct without using underlying records