Bioequivalence and Bioavailability Forum

Dear VSP
Please explain what do you mean by dose failure in case of sub-lingual film.
IMHO dose failure = post dose = drop-out => replacement not possible if not explicitly permitted by the protocol.

Hi VSP,

❝ […] replacing a subject withdrawn for dose failure (ex., Sub-lingual Film) with a stand-by subject will be considered contradiction/violation of protocol?

Only you know the protocol – so what are you expecting from us? I agree with what Dan wrote above.
A dropout is a dropout is a dropout.

The procedure of “replacing” subjects opens a can of worms (related to the statistical treatment of multi-group studies). The periods of these subjects are different from the other subjects. The loss in power in a properly planned study is usually negligible. If you don’t believe me, add some subjects to the estimated sample size in order to compensate for the expected dropout-rate.

Another story are “reserve subjects”. They signed the ICF, comply with the inclusion criteria, are screened, etc. Sometimes a volunteer gets ill before the first administration or withdraws consent (‘I don’t like the face of the PI, this place sucks, my neighbor last last night snored, …’). Then one of the “reserves” jumps in. Hence, in many CROs subjects are randomized in the morning of the first day and not at hospitalization. That’s fine as long as you have an SOP in place and/or describe it in the protocol.

Dear VSP, all,

❝ (...) dose failure (ex., Sub-lingual Film) (...)

This caught my attention.
What is dose failure for this type of product, and how is it verified??

The subling films dissolve rapidly so I am thinking the classical mouth check with tongue depressor and penlight does not achieve much. If there's nothing to see, then it means the subject took the dose or that she/he didn't

Perhaps something else was meant?? I am a curious person so please pardon me for going a little off topic.