Bioequivalence and Bioavailability Forum

Dear Helmut,

❝ Don’t agree. It’s easy enough through simulations (i.e., θ₀ 0.95, CV_intra 40%, n 12, power 82.2%).

Since no study will decide BE on Cmax alone this is wasting of time I think. The sample size estimation for the other metric AUC will give you with certainty a higher number of needed subjects.

❝ What puzzles me is the lacking consideration of the patient’s risk. With a θ₀ at the limits of the acceptance range by definition 50% of studies will pass – independent from CV and sample size.

As said above no study will decide BE on Cmax alone, but also on AUC.
The decision on AUC has an alpha=0.05. Combining it with the decision on Cmax will not raise the error probability if AUC is truly not BE, I think:
Only a half of the studies which conclude erroneously BE based on AUC will conclude also BE based on Cmax if true ratio for Cmax is on the BE limits. Thus the overall alpha should be <0.05. Correct me if I’m wrong.

But ... In case of 'true BE based on AUC' you are right. Then the overall decision is solely based on the point estimator of Cmax within 80-125%.
Seems the Canadians see this more as a problem of the power of the AUC decision than as a problem of patient’s risk.