GVP Module IX: Signal Management Knowledge Assessment

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

Wait for complete certainty before escalating or considering action Ignore the signal until it becomes statistically significant Consider a rapid, proportionate response because the consequences of delay may be substantial Close the signal because uncertainty prevents any professional decision

Detection determines the regulatory action, whereas validation only records the date of the alert Detection identifies an observation that may warrant attention, whereas validation determines whether it meets the criteria to be treated as a signal Detection applies only to spontaneous reports, whereas validation applies only to clinical trials Detection establishes causality, whereas validation determines the seriousness of the adverse event

Keep it within the routine periodic workflow until the next scheduled review Wait until all possible evidence streams are complete Use the escalation route for accelerated medical, pharmacovigilance or regulatory assessment as appropriate Close the signal temporarily to avoid disrupting normal procedures

Accurate duplicate handling can prevent artificial amplification of an apparent reporting pattern High-quality case processing eliminates the need for aggregate assessment Removing incomplete cases always improves signal sensitivity Case quality has no effect on the interpretation of product-event patterns

Personally performing every statistical and epidemiological analysis Replacing all scientific specialists in making detailed case-level assessments Maintaining oversight of significant issues, escalation, important decisions and system effectiveness Approving every individual case before it enters the safety database

Potential seriousness and medical importance Vulnerability of the affected population Potential impact on the benefit-risk balance A numerical score without consideration of clinical judgement

The first report ever associating a medicine with an unrelated event Evidence that an established reaction occurs at a different dose relationship or through an important interaction A statistical alert caused solely by a reporting-system change A duplicate case entered into two databases

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

The issue is removed from all cumulative safety evaluation The signal is closed only if a regulatory action is taken The evidence refutes the association or the issue is adequately characterised or incorporated into an established risk, with documented rationale The signal is deleted to prevent it from reappearing in future reviews