Bioequivalence and Bioavailability Forum

Hi Helmut,

❝ I wonder if you are not overdoing standardization.

Damned, I am discovered ! I agree this is close to nitpicking.
The intention was just to give some math arguments to the fact that a fixed rule like "±5%" is not always the best choice.
The best choice would be not allowing any deviation, but not sure that the clinical staff would appreciate it , therefore the need for a compromise...
Practically, I often use a ±10% acceptance (for a classical IR formulation). However, this can be adapted depending on the context.

❝ I would be reluctant to use the term “bias”, since we don’t have good (any?) evidence of the underlying distribution of concentrations. Which location parameter should we use? The arithmetic or geo­metric mean, the median (see this post)?

I was not thinking of the deviation from any point estimate (for which I am generally more in favor of the geometric mean) but of the shift expected for the true concentration (so "bias" looks appropriate to me) due to the time deviation.

❝ Sampling too early would ring my alarm bell concerning the proper per­for­mance of the clinical part.

Indeed, this unusual case was just a theoretical consideration to maximize the math impact of the example.