Nothing Is Expected on a First-in-Human

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

About 2 minutes. Free, in your language, no account needed.

The empty reference document

In a first-in-human study, the product has never been given to a person. There is no human safety experience to list. The Reference Safety Information may contain almost nothing, or nothing at all.

The consequence follows directly from the rule: essentially every adverse event that is serious and assessed as related is also unexpected, and is therefore a SUSAR.

This is intended, not a defect

Early-phase studies are where unknown harms appear, and the reporting system is deliberately maximally sensitive there. The volume of expedited reports from a first-in-human study is not evidence that something is wrong with the product or with your process.

The mistake people make

The mistake is to reason from animal data. A finding in a toxicology study is not human Reference Safety Information. Something observed in rats at high dose is not an expected human adverse reaction, and events of that type in the trial are still unexpected.

Similarly, an event well known for the drug class is not expected for this product unless this product's own RSI lists it.

What this means in practice

Plan for it. A first-in-human study with a thin RSI will generate expedited reports at a rate that will surprise anyone who has only worked on late-phase studies. Resourcing that, rather than finding reasons not to report, is the correct response.

As the brochure fills

As the program progresses and the Investigator's Brochure is updated, more events become expected, and the expedited volume falls. That transition happens on the date the new RSI takes effect, not gradually and not retrospectively.