Bioequivalence and Bioavailability Forum

Hi,

I am planning a study where I want to include the time until a pre-defined plasma concentration threshold is reached as a PK parameter. Two options/methods for defining this parameter has been discussed:

A) The simplest approach would be to use the first sampling time-point where the concentration exceeds the threshold.

B) The other approach would be to use linear interpolation to find a more precise estimate of the time the concentration actually crosses the threshold.

From a methodological point of view, I find option B somewhat more appealing, as this would give a more "correct" result. However, there are a few arguments making me lean more towards option A anyhow, including:

1. Option A requires no imputation/assumptions of plasma levels between samples.

2. Data based on actual sampling times will be analogous to Tmax and perhaps more recognizable/acceptable by the authorities.

3. I also plan to present the percentage of subjects exceeding the threshold value at each sampling timepoint. A definition according to option A would better correspond with this analysis.


-Is there a "standard" approach?
-Does anyone have any advice on the best approach or experience regarding regulatory acceptability of data?

Thanks,
/Martin