Bioequivalence and Bioavailability Forum

Hi Louis,

❝ Did anybody encounter a situation with a BE study with more than 2 arms (i.e. Ref 1, Ref 2, and Test)? I understand it might sound weird but it can be a real case. Is there any adjustment for the sample size calculation in this instance? Any other adjustments, like for the power, etc?

This is a fairly common scenario.
You can dimension it conservatively by assuming the worst metric and its CV.
Multiplicity adjustment could be very relevant in this case (you want BE for test against both refs), but there is no obvious way to do it because things can be somewhat correlated. If you look at them separately and assume no correlation then you can easily power both tests to 90% and expect about an 80% chance of success if your assumptions are correct. And so forth. Note also for EU you are often removing the irrelevant data serially, but you aren't doing so for the US analysis. I am not aware of anyone having ever qualified a healthy way to deal with this aspect at the sample size stage (but I am aware of people less closely connected to real life having done -or should I say 'tried'- such a thing).
How does it look at your end, is the between-unit CV (total) for the potencies different between the two refs?