Bioequivalence and Bioavailability Forum

Dear all,

We are planning to conduct a comparative pharmacokinetic (PK) study including two test products and one comparator.
According to Section 2.2.5.2 “Multiple Test Products” of ICH M13A, when the objective is to demonstrate bioequivalence (BE) for any of the test formulations, a multiplicity (alpha) adjustment may be required.

Further clarification on this topic is provided in the M13A Q&A document.
In our study, we intend to apply a hierarchical testing approach, considering that one of the formulations has shown more promising in-vitro results.
Specifically, our plan is to first assess BE between Formulation 1 and the comparator. If BE is demonstrated, we would then proceed to assess Formulation 2 versus the comparator.

Could you please confirm whether, under this hierarchical testing approach, an alpha adjustment is required, or if it can be omitted in accordance with the statement from the M13A Q&A:

“Formally, there is no need for multiplicity correction for each individual test, but the type I error (consumer risk) is still controlled.”

Thank you very much for your clarification.

Kind regards,
Mikkabel