Bioequivalence and Bioavailability Forum

Dear Martin,

thanks for sharing your opinion .
Let me ask some puzzled things further.

❝ - for visualizing individual concentration time profiles I treat values <LLQ as missing.

Is this also true for intermediate (between two values >LLOQ) or beginning values <LLOQ?

❝ for average concentration time profiles I use also arithmetic means [...] note that values of zero are not possible when using geometric means.

If you use the definition geom. mean=n-th root of the product of the values, you can account for zero's .

But then every time point with only one zero for a volunteer results in zero geometric mean. Not so good I think.
Omitting zero values results on the other hand in a geometric mean which is in certain cases to high for my feeling. F.i. all but one value <LLOQ would then result in a mean = that value not <LLOQ.

Nevertheless the geometric mean was recommended in the pioneering paper
Sauter R, Steinijans VW, Diletti E, Böhm A, Schulz HU.
Presentation of results from bioequivalence studies.
Int J Clin Pharmacol Ther Toxicol. 1992 Jul;30(7):233-56.

and recently in the book
D Hauschke, V Steinijans and I Pigeot
Bioequivalence Studies in Drug Development
John Wiley & Sons, Chichester (2007), chapter 6

I assume this is because the authors assume log-normal distribution of concentration values. But both literature do not explicitly explain how they deal with LLOQ.

OK, the whole is only for illustrative purposes in the study reports, but nevertheless a standardization deems necessary.