Bioequivalence and Bioavailability Forum

Dear Dr Brijesh,

❝ But are there any guidelines for ethical considerations for this?

Not that I know of. But you need to justify your sample size. Taking care of drop-outs is part of it (it would be unethical to fail to demonstrate BE just because 2 subjects dropped from the study). On the other hand you can (or rather, should) adapt the number of extra subjects to the known tolerability of the drug, and to the study design. If it is known to be create emesis, or if you have more than 2 periods, or a long wash-out, you will add more subjects. If the tolerability is known to be good and the study is "standard", you may not need 10 % extra.

❝ And if those extrasubjects also complete the study, what is the justification for including/excluding these extra subjects' samples for bioanalysis including theirdata in statistical analysis. Do we have any regulatory and guidelines for this?

The EU guideline is very clear:
The data from all treated subjects should be treated equally. It is not acceptable to have a protocol which specifies that 'spare' subjects will be included in the analysis only if needed as replacements for other subjects who have been excluded. It should be planned that all treated subjects should be included in the analysis, even if there are no drop-outs.

Regards
Ohlbe