Bioequivalence and Bioavailability Forum

Hi Helmut,

I forgot to answer...

❝ When it comes to a test, see the end of Section 1 in this post (EUFEPS workshop, Bonn, June 2013).

Thanks, I more and more come to the same conclusion...

❝ ❝ Is there a way to define quantitative thresholds based on the PK (or even PD?) of the compound (i.e. concentration should not change by more than x%)?

❝ ... In the regression we assess the last three pre-dose concentrations, which – to some extent – takes the inter-occasion variability into account. Of course, we may fall into the trap mentioned previously.

I was thinking about the following: When we do a linear regression log(y) = a*x + b (+ eps), then the interpretation of a is that when x changes by 1 unit, then y changes (on average) by (exp(a) - 1) * 100%. That means we can make a statement about %-change in pre-dose concentration and we could maybe set relevance limits for this change. But the trap that you mentioned is I guess still valid and does not go away (we may argue not with the estimated coefficient of a but with some upper CI/PI limit (e.g. 68%), but nevertheless the issue remains).

❝ When we set a threshold of \(\small{x\%}\), we are essentially believing that the last two pre-dose concentrations are the true ones, right? Of course, that’s another trap.

Yes, agreed.

One more question: In your lecture you state that one should calculate gMean as well. Are you also calculating gMean ratios, i.e. calculating point estimates for the comparison of different time points (e.g. each vs. last)?

Best regards,
Ben.