Bioequivalence and Bioavailability Forum

Dear All,

I am currently contributing as a statistician to the design of a drug interaction study. For this reason I went through the EMA Note for Guidance into operation, but also the EMA draft Guideline on this topic.

I was quite surprised to notice that the clear details provided in section 5.1.2 of the Guidance into operation seem not present in the draft Guideline. In particular, it is not specified how the lack of a relevant interaction should be demonstrated in a conventional interaction study (more details are provided on population pharmacokinetic analysis in the section 5.4.7 of the draft Guideline).

Furthermore, the analyses requested in the following part of the section 5.5 of the draft Guideline are not very clear to me:

The interaction effect should be calculated and the change in relevant pharmacokinetic parameters presented. Individual changes in pharmacokinetic parameters should be listed together with descriptive statistics, including the 90% confidence interval and the 95% prediction interval for the interaction effect.

Any help regarding these issues would be much appreciated.