Bioequivalence and Bioavailability Forum

Dear all,

1. I am not a statistician and struggle to grasp the concept of type one error inflation in the reference-scaled approach. We basically do the same things as in the usual average bioequivalence where we are able to preserve TIE at 5%, but when we expand CI, we have got TIE inflation. What is behind this inflation, philosophically and mathematically? I also bumped into this discussion where some ever argue about whether this concept even exists. https://daniellakens.blogspot.com/2016/12/why-type-1-errors-are-more-important.html I assume this is not related to multiple testing. Also, we have a statistical concept, but do we have any real proof of this concept? Does anyone know products that were initially registered and then withdrawn from the market because their initial bioequivalence had been due to the inflation TIE.
2 Maybe this is not related to SABE but two-stage design, but anyway. What prevents us from using Bonferroni correction in the two-stage adaptive design, instead of rather complicated other statistical approaches?

Thanks in advance