09 Feb Day 0 In Local Literature Screening
In January 2023 EMA posted an interesting interpretation of the Pharmacovigilance Inspectors Working Group regarding Day 0 in the context of Individual Case Safety Reports (ICSRs) found in physical/hard copy local medical journals:
“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.”
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 articles were read, matched with the selected search terms, assessment was carried out and evaluation was made about the presence of an ICSR. Hence, the mere receipt of the physical copies was not considered as the point of awareness of the minimum criteria.
In essence, the new interpretation of EMA equals searching in physical copy local journals to a search in an electronic database. This shortens the timelines in which Marketing Authorisation Holders (MAHs) and their vendors need to organise the activities of technical receiving, reviewing and assessing hard copies as this time is counted now towards the overall reporting deadline.
Both interpretations claim to step on reading the Guideline on good pharmacovigilance practices (GVP), Module VI. According to GVP (VI.B.7.) for ICSRs described in medical literature, the clock starts (day zero) with awareness of a publication containing the minimum criteria. According to GVP VI.App.2.7. day zero is the date on which an organisation becomes aware of a publication containing the minimum information for an ICSR to qualify for submission. Awareness of a publication includes any personnel of that organisation, or third parties with contractual arrangements with the organisation. 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.
It is clear that EMA aims at making sure that MAH’s organisation does not allow for delays between the point of having available literature hard copies and their respective processing. However, there are some practical implications related to paper literature: the unpredictable arrival date and volume of hard copy medical journals. For MAHs that means maintaining significant stand-by resources in order to do the processing as soon as possible upon arrival. It is questionable though what the actual impact on patient safety would be, considering that at the time we read a paper article the case in such local literature or reference databases is already at least three-months old.