Bioequivalence and Bioavailability Forum

Hi Felipe,

❝ In case of performing a study with an endogenous substances such as hormones what would be the approach to justify an ocurrance of a sequence effect for HA? Premisse: You have an adequate washout period, and you have found this effect....

Endogenous compounds are of a nasty kind. I can only suggest to keep in mind that there might be a feedback loop. It’s not only laking concentrations in the higher periods which counts. Keep the wash­out as long a possible. If you followed all that (as you did), maybe the Type I Error hit (you got a significant effect, which is not there). You can try to claim that. Not sure whether regulators(s) will buy it.

If you want to be sure, I’m afraid there is no way around a parallel design. In all (!) crossover studies of biosimilars I’m aware of there was a significant sequence effect. Something happened to the body. Given that it is beyond me why biosimilar-guidelines recommend a crossover design as the “gold standard”.

❝ Some stats that I have contact suggested a bootstrap analysis to check if it was a random or a real effect...

Sounds like black magic to me. But I’m not a statistician.