Bioequivalence and Bioavailability Forum

Dear Kim

Who define HVD? Does it subject to the regulator in each country? Is it useless? if you known you are going to run study with 40% CV in Cmax but your regulator don't allow to extent the BE acceptance criteria. In this case, HVD is only the information telling you that you have to run the risky project if the number of subjects are not enough.

The first paper you referred is MR and The evidence that I have with standard design, IR, fasting condition there is no one which the CV exceed 20% that's why I don't think this drug (for above condition) is a high CV drug.

BTW: Combined CV is an option. Suppose that if you have 7 papers support the CV is around 10-15% CV but there is one paper that have 27% CV. How do you set the CV? There are many way to set CV into the formula e.g. select from median or select from mode or subjective setting up or even assuming and etc. Finally, beside the sample size calculation, the number of subjects also depend on your many restrictions e.g. your team discussion, budget, trust of your evidence, sponsor opinion and etc... that you and your team should be the best one who know about. It is the basically statistical idea. That's why there are a number of statistics textbooks stated about sample size determination under budget limitation.

Regards,

Boonchai L.