Bioequivalence and Bioavailability Forum

Dear all,

May I ask something about 90%CI and ANOVA, when bioequivalence study have to be conducted under both of fasting and fed condition and the design of four-way cross-over was considered.

According to "GUIDELINE ON THE INVESTIGATION OF BIOEQUIVALENCE" both of draft and new version allowed the design of four-way cross-over to be able to be used.

As everyone known, the 90%CI was calculated from formula that contains the MSE from the ANOVA.

My question are

1. Are the 90%CI of geometric mean ratio of test/reference for fasting and fed state calculated from the same MSE? or even the ratio food/fasting and 90%CI for test and reference, Is it the same MSE? Because there is only one ANOVA.
   
2. 2. If this design is not suitable for BE study, why they still recommend to use?

Best Regards,

BL

I am looking for your suggestion and Thanks in advance for your reply.