Listed But Still Unexpected

Part of Pharmacovigilance and Drug Safety (PV) Training: Expectedness.

About 1 minutes. Free, in your language, no account needed.

Appearing in the document is not always enough

An event can be named in the reference document and still be unexpected, when what happened differs from what is described in nature, specificity, severity or outcome.

Specificity

The RSI lists "hepatic disorders". The patient developed fulminant hepatic failure requiring transplantation. The specific, severe event is not adequately described by the general term, and is unexpected.

The rule works the other way too. A document listing "acute hepatic failure" does not make every mild transaminase rise expected, though in practice a general term is the more common case.

Severity and outcome

An event listed as occurring in a mild and self-limiting form is not expected when it occurs fatally. A listed rash does not make Stevens-Johnson syndrome expected.

Why this matters

Because this is the judgment that catches genuinely new information about a product. A mechanical match on the term alone would let a qualitative change hide inside an existing listing, which is precisely the situation where a signal is most valuable and most easily missed.

How to apply it without over-reporting

Ask whether a reader of the reference document would have anticipated this event, as it actually occurred, from what is written there. If the document would have led them to expect something materially milder, or of a different character, treat it as unexpected.

Document the reasoning. An unexpectedness determination that departs from a plain reading of a listed term is exactly the kind of decision a reviewer will want to see explained.