Signal Validation is the activity of verifying the reliability and completeness of the information supporting a potential signal. Here’s how it’s done according to GVP.
Signal Validation is the activity of confirming or not the existence of a new or changed cause/effect relationship on the basis of the documentation collected during the Signal Detection. Signal Validation aims to verify that the information collected in the previous phase is complete and sufficient for signal validation. It is the second phase of Signal Management: it follows the Signal Detection, i.e. the signal research activity that the companies holding the MA are required to carry out to comply with the pharmacovigilance regulations.
According to the Good Pharmacovigilance Practices – GVP, to carry out the validation of the signal, it is necessary to take into consideration the previous data such as the information reported in the Summary of Product Characteristics (SPC), in the Package Leaflet (FI), in the Risk Management Plan (RMP), in the report security update periodical (PSUR) or in any other source prior to the detection of the signal.
In addition, the straightness of the evidence should be analyzed taking into account elements such as the number of cases, data quality and consistency, possible mechanism based on biological and pharmacological plausibility, and any supporting data.
The context and clinical relevance must also be analyzed, for which elements such as the severity of the reaction, outcome, possible interactions, or reaction on special populations are investigated.
In addition to these data, other sources may provide additional evidence, including clinical data, findings on similar cases in the scientific literature, information on the epidemiology of the adverse reaction or underlying disease, experimental and/or non-clinical results, or data from health databases.
However, in addition to the indications given in the GVP, there is no common standard that indicates how to analyze the data or how to make a report, though, for example, tables or evaluation grids. It will therefore be the responsibility of the MAH to establish the values within which to validate or not a signal. If there are uncertainties, it is possible to reserve the right to validate a signal later in light of new evidence.
The safety database allows reliable collection of data related to adverse events, protecting the pharmacovigilant from the risk of errors or omissions of information. Inside the case it is possible to insert the indication of a possible signal, through a specific flag, the reference of which can be extracted in useful reports during the validation phase of the signal itself.
The Business Intelligence module, thanks to the quantitative analyses based on indicators of statistical disproportionality, such as ROR, PRR and RR, allows for rapid feedback on drug/reaction correlations that present a statistically disproportional result.