What is vaccinovigilance? Signal analysis and validation (3/3)

In order to perform correct signal detection, it is necessary to analyze the global safety database regularly and systematically for each vaccine, on all AEFI collected with the different frequencies depending on the type of vaccine (single, combined, subject to additional monitoring).

Particular attention must be paid to the Designated Medical Events, i.e. rare events, fatal events and case clusters. Adverse events are evaluated by type, by correspondence with standard classifications, by lot, taking into consideration any complaints or production defects, variation in the reporting frequency of a known event with respect to the expected (observed vs expected), concurrent vaccination campaigns. Data are stratified by gender, age groups, geographical area, seasonality.
It is important to compare with other databases (e.g. VAERS), to check literature data and period data. As with drugs, event/vaccine pairs with a frequency greater than a predefined threshold can constitute a signal. An additional criterium for signal detection is the use of TTO (Time to Onset); this criterion examines the time of onset of the adverse event: TTO in the 60 days post vaccine significantly different from the TTO of the same event with other vaccines and / or other events of the same vaccine.
The signal must be analyzed using both statistical and traditional methods.

Signal validation is a long process: after receiving the adverse event, it is imported into the database. Therefore, a signal detection is performed on a valid sample and the data and information collected are evaluated. In the event that a significant signal is found, a communication is made to the competent authorities and appropriate corrective measures will be taken.

All that emerges from the analysis of the signals is discussed in periodic safety reports that represent the state of knowledge about the vaccine and have as a result the continuous updating of the prescriptive information. This active vaccinovigilance work continues throughout the life of the product and is constantly monitored by regulatory authorities who can approve/reject this report.

The reports are:

• Periodic Benefit Risk Evaluation Report (PBRER): describes the benefit/risk profile of a product in the post-marketing phase and represents a critical, concise and complete analysis of safety and effectiveness with respect to what was previously known
• Risk Management Plan (RMP): describes the state of the art of knowledge on all aspects of a product, describes the known risks, potential risks and missing information and implements appropriate mitigation systems for these risks (Post- Authorization Safety Study – PASS, Safety Communications – DHPC / DIL, Regulatory actions such as RCP/FI change, lot collection etc., educational materials and specific questionnaires by type of event) regarding the monitoring of rare or lot-related reactions, of the onset of autoimmune diseases or delayed onset reactions. The RMPs are a valid, proactive tool for identifying safety signals earlier and earlier.