Bioequivalence and Bioavailability Forum

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❝ […] replacing a subject withdrawn for dose failure (ex., Sub-lingual Film) with a stand-by subject will be considered contradiction/violation of protocol?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