Guideline on good pharmacovigilance practices (GVP) – Module IX (Rev 1)
an intervention and an event or set of related events, either adverse or beneficial, that is judged to be
of sufficient likelihood to justify verificatory action [IR Art 19(1)].
New aspects of a known association may include changes in the frequency, distribution (e.g. gender,
age and country), duration, severity or outcome of the adverse reaction.
A signal often relates to all medicinal products containing the same active substance, including
combination products. Certain signals may only be relevant for a particular medicinal product or in a
specific indication, strength, pharmaceutical form or route of administration whereas some signals may
apply to a whole class of medicinal products.
For the purpose of monitoring data in the EudraVigilance database (also referred to as
‘EudraVigilance’), only signals related to an adverse reaction shall be considered [IR Art 19(1)].
Signal management process: A set of activities performed to determine whether, based on an
examination of individual case safety reports (ICSRs), aggregated data from active surveillance
systems or studies, scientific literature information or other data sources, there are new risks
associated with an active substance or a medicinal product or whether known risks have changed, as
well as any related recommendations, decisions, communications and tracking.
The EU signal management process includes the following activities: signal detection, signal validation,
signal confirmation, signal analysis and prioritisation, signal assessment and recommendation for
action [IR Art 21(1)] (see IX.A.1.2.).
Signal prioritisation: The process, continuously performed throughout signal management, which
aims to identify those signals suggesting risks with a potential important patients’ or public health
impact or which may significantly affect the risk-benefit balance of the medicinal product and thus
require urgent attention and management without delay.
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Signal detection: The process of looking for and/or identifying signals using data from any source.
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Signal validation: The process of evaluating the data supporting the detected signal in order to verify
that the available documentation contains sufficient evidence demonstrating the existence of a new
potentially causal association, or a new aspect of a known association, and therefore justifies further
analysis of the signal [IR Art 21(1)].
This evaluation should take into account the strength of the evidence, the clinical relevance and the
previous awareness of the association (see IX.B.3.).
The extent of evaluation performed during signal validation versus further assessment may vary
according to the organisation’s internal procedures.
Validated signal: A signal for which the signal validation process has verified that the available
documentation contains sufficient evidence demonstrating the existence of a new potentially causal
association, or a new aspect of a known association, and therefore justifies further analysis of the
signal.
Non-validated signal: A signal for which the signal validation process has led to the conclusion that
the available documentation at that point in time does not contain sufficient evidence demonstrating
the existence of a new potentially causal association, or a new aspect of a known association, and that
therefore further analysis of the signal is not warranted.
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Based on SCOPE Work Package 5 – Signal Management - Best Practice Guide (www.scopejointaction.eu)
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Council for International Organizations of Medical Sciences (CIOMS). Report of CIOMS Working Group VIII on Practical
Aspects of Signal Detection in Pharmacovigilance. Geneva: CIOMS; 2010.
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SCOPE Work Package 5 – Signal Management - Best Practice Guide (www.scopejointaction.eu)