Bioequivalence and Bioavailability Forum

Dear Yura

❝ So, is it right: for ABEL I should adjust Type I Error (alpha)

To protect against an alpha-inflation which otherwise may occure, it's exactly what we recommend in our paper¹.

❝ or in other words to decrease to 0.025?

That's not what we recommend in our paper. We recommend to adjust alpha based on the outcome of the study. For details see our paper, especially the examples.

❝ What I can do if I’ll use RSABE

Here I can't help since nobody has thoroughly investigated alpha inflation of the FDA recommended method for scaled ABE. This has to do with the controversies regarding where to locate the region of the type I error. See the paper of Davit et al.²

❝ (because here alpha is absent in formula)?

That's not correct.
Alpha is contained in the request to calculate 95% upper confidence limit of the linearized RSABE criterion. If you adjust alpha you have to calculate 1-alpha_adj upper confidence limit. Looking at the SAS code change all alpha=0.1 to 2*alpha_adj you will use.
But as already said: Nobody knows or can calculate the value of alpha_adj to use.

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1. Labes D, Schütz H. Inflation of Type I Error in the Evaluation of Scaled Average Bioequivalence, and a Method for its Control. Pharm Res. 2016;33(11):2805–14. doi:10.1007/s11095-016-2006-1. full-text view-only
   
2. Davit et al. "Implementation of a Reference-Scaled Average Bioequivalence Approach for Highly Variable Generic Drug Products by the US Food and Drug Administration"
   AAPS Journal, Vol. 14, No. 4, December 2012

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