Bioequivalence and Bioavailability Forum

Hi ElMaestro!

❝ ❝ Given the above (and assuming you have stated nothing in the protocol) I would write an amendment or at least a note to file stating that the subject will be taken out from the confirmatory assessment of bioequivalence. You can present the complete data set (with the subject) in an exploratory manner. Personally I would assume the worst case scenario and take the subject out (no further dosing, but samples analyzed).

❝

❝ Are you sure about this?

I’m never sure (some kind of professional deformation).

❝ If nothing is written in the protocol about excluding those who chew, and everything else is done according to SOPs then I would think:

❝ 1. The subject fulfils the PP and ITT criteria.

Agree.

❝ 2. The subject should not be eliminated from analysis or terminated from study, at least as long as the chewing does not cause safety concerns.

Well. If the posology does not specifically state that chewing is allowed, I would assume the worst. I would not expect a large impact on IR formulations but MR are of a different breed. If the subject is kept in the data set (following the protocol) this may blew the study. I would rather follow common sense: “Oops, the volunteer chewed the tablet – we haven’t thought about that – might have an impact on absorption – do we want to compare e.g. Test_chewed vs. Reference_unchewed? – write an amendment.”

❝ 3. The clinic should update SOPs so that this doesn't happen in the future.

Agree.