Usually, signals are detected when assessing and reviewing individual case safety reports (ICSR) in an individual or cumulative way. In relation to this, the signal management process can be viewed as a set of activities the primary goal of which is to determine whether, based on an examination of ICSRs (including combined data from active surveillance systems or studies, literature information or other data sources) there are new hazards associated with an active medicinal product or whether already discovered and known risks have altered.
The signal management process covers several steps – detection, validation, confirmation, analysis and prioritisation, assessment and recommendation for action.
- Signal detection – it contains a mixture of statistical methods and review of individual case safety reports, as well as any relevant source of information
- Signal validation – this is the process which encompasses evaluation of the data that supports the detected signal. This evaluation is carried out in order to verify that the available documentation involves accurate and enough evidence demonstrating the existence of a new potentially causal association or a new aspect of an already known association, and respectively advocates and explains any additional and future analysis. During this step of the signal management, the appointed personnel should take into account the clinical importance of the signal, its previous awareness, the biological and temporal plausibility and any relevant sources of information supporting the association. Signals validated by the European Medicines Agency (EMA) or Member States are entered in the European Pharmacovigilance Issues Tracking Tool (EPITT).
- Signal confirmation – it is a procedure that includes communication via EPITT (within a strict timeframe of 30 days of its receipt by the PRAC Rapporteur or the lead Member State) confirming that the validated signal is supposed be analysed and prioritised by the PRAC.
- Signal analysis and prioritisation –this phase focuses on the potential effect of the signal on the benefit-risk profile of medicinal products. The prioritisation points out the deadline for submission and assessment of data.
- Signal assessment – it stands for the scientific evaluation of the available evidence (including additional data from MAHs when applicable and necessary). Once the signal is assessed (evaluated) and prioritised as “confirmed”, additional information must be collected in order to perform further signal evaluation.
Here it is crucial to underline that every signal which has been “confirmed” is assessed in terms of the following criteria or aspects:
– Causality
– Frequency
– Clinical implications
– Preventability
Furthermore, taking into consideration the suspected signal’s evaluation outcome, one may choose to elevate it to the status of either “potential” or “identified risk”.
This signal evaluation process is intimately tied to risk identification and may result into the feeding of the signal into the risk mitigation/management planning processes at your company.
If you are interested in the topic of Signal Detection, you may like to view our Pharmacovigilance Advanced training.