Bioequivalence and Bioavailability Forum

Dear all,

maybe this article is of interest:

Helmut Schütz , Divan A Burger , Erik Cobo , David D Dubins , Tibor Farkás, Detlew Labes , Benjamin Lang, Jordi Ocaña, Arne Ring , Anastasia Shitova , Volodymyr Stus, Michael Tomashevskiy. Group-by-Treatment Interaction Effects in Comparative Bioavailability Studies. AAPS J. 2024; 26(3): 50. doi:10.1208/s12248-024-00921-x. Open Access. Supplementary Material.

⅔ of the authors are members of the forum...

I’m not sure whether the results of the article will change the respective section of ICH M13A, which in the draft states:

Sample size requirements and/or study logistics may necessitate studies to be conducted with groups of subjects. The BE study should be designed to minimise the group effect in the study. The combination of multiple factors may complicate the designation of group.
BE should be determined based on the overall treatment effect in the whole study population. In general, the assessment of BE in the whole study population should be done without including the Group by Treatment interaction term in the model, but applicants may also use other pre-specified models, as appropriate. However, the appropriateness of the statistical model should be evaluated to account for the multi-group nature of the BE study. Applicants should evaluate potential for heterogeneity of treatment effect across groups, i.e., Group by Treatment interaction. If the Group by Treatment interaction is significant, this should be reported and the root cause of the Group by Treatment interaction should be investigated to the extent possible. Substantial differences in the treatment effect for PK parameters across groups should be evaluated. Further analysis and interpretation may be warranted in case heterogeneity across groups is observed.
(my emphasis)

If not, at least you can use the article in an argument with regulators… See also the meta-study in this article, which I regularly update with new data.