Bioequivalence and Bioavailability Forum

Dear all,

we know for a good while that under certain conditions the Type I Error (TIE) might be inflated. However, seemingly European assessors were either not aware of it or ignored it. Last week I saw a deficiency letter (don’t ask for the country):

… in case of a value of 30% < CV_RR <45%, it is recommended to check the control of the patient's risk type I error at the level of 5%. If an alpha adjustment is necessary, it is recommended that a BE estimate for the new CI of the T/R ratio be submitted to meet the extended bounds.

Kudos! Almost correct. The area of inflated TIEs may reach below 30% and only rarely (say, for a 4-period full replicate in 24 subjects) to 45%.