Marketing authorisation holders (MAHs) are requested to review and assess reports of suspected adverse reactions from medical literature to identify and record individual case safety reports (ICSRs). For ICSRs described in medical literature, the clock starts (Day zero) with awareness of a publication containing the minimum criteria. In pharmacovigilance, a recent interpretation by the Pharmacovigilance Inspectors Working Group (Ph IWG) regarding Day 0 in the context of ICSRs found in physical/hard copy local medical journalshas caused concern and confusion among professionals. In January 2023, the European Medicines Agency (EMA) posted this interpretation, which states that for ICSRs described in the medical literature containing the minimum criteria, the clock starts (day zero) when the MAH receives the physical/hard copy local journal. This is equal to performing a literature search in an electronic database.
EMA position on Day zero
“For ICSRs, described in the medical literature containing the minimum criteria, the clock starts (day zero) on the day when the physical/hard copy local journal is received by the organisation/Marketing authorisation holder, and this should be considered equal to performing a literature search in an electronic database.”
Therefore, the clock starts (day zero) for regulatory reporting purposes when the marketing authorisation holder (MAH) receives the physical copy local journal. Awareness of a publication includes any personnel of the MAH or third parties with contractual arrangements with the MAH. In essence, the new interpretation of EMA equals searching in physical copy local journals to a search in an electronic database.
Where did the panic come from?
Such a definition could not but surprise pharmacovigilance professionals—especially those who work with medical literature every day. For example, you can get a 200-300 page physical/hard copy local journal on Monday. And rejoice in the fact that day zero began on the same day. But is it possible to at least read such a volume of information?
So far, the alternative understanding was “Day 0 at awareness”, i.e., when the assessment of an article comes to a result. Such awareness supposes that the papers were read and matched with the selected search terms, the review was carried out, and an evaluation was made about the presence of an ICSR. Hence, the mere receipt of the physical copies was not considered the point of awareness of the minimum criteria.
Maybe not everything is so bad?
But we would like to look at such an interpretation from the EMA and Ph IWG from the other side.
According to EMA, for articles that have been ordered as a result of literature search results, day zero is the date when the minimum information for an ICSR to be valid is available. Organisations should take appropriate measures to obtain articles promptly in order to confirm the validity of a case.
Perhaps the EMA and Ph IWG just gave their interpretation of the last point? At the very least, additional clarifications are expected from the EMA.
Afterword from DrugCard
The decline in printed medical publications proves we’re all about that digital life now. It’s not just because we love fancy gadgets, but also because we care about the environment – deforestation is not a good look. So, it’s only natural that pharmacovigilance hops on the digital bandwagon and starts monitoring medical literature online. We can’t stress enough how crucial patient safety is, and the key to achieving that is by getting the necessary info quickly. Unfortunately, relying on the manual reading of medical literature is about as effective as trying to type with your toes. That’s why pharmacovigilance peeps must embrace digital tools to keep patients safe and sound.