Bioequivalence and Bioavailability Forum

Hello everyone,

Thank you for maintaining this forum, it is very helpful. I am another novice attempting to get a grasp of PK. After a few sort or regular courses and a lot of googling, I got to a level where I have some understanding, but still a lot of questions. I hope that one day I will be able to look back and laugh at my questions.
My most recent roadblocks are the following:
1) Text in WinNonlin help menu: "Measures for each individual should be displayed in parallel for the formulations tested. In particular, for each BE measure the ratio of the individual geometric mean of the T product to the individual geometric mean of the R product should be tabulated side by side for each subject."
I understand "for each BE measure" to refer perhaps to let's say Cmax. What I don't understand is what geometric mean could there be for each subject? Are they referring to replicate studies? If the study is not replicate, then one should tabulate simply the BE measure (such as Cmax, AUC etc) for each subject?
2) When using the BE wizard in WinNonlin, in the "Bioequivalence Fixed Effects" window, what does "Fixed Effect Confidence Level" refer to? For a crossover (1 treatment and reference) what are the fixed effects?
3) I read this example: http://www.ajpe.org/legacy/pdfs/aj630215.pdf and I was able to understand the step-by-step calculations, but when looking at the WinNonlin output, I don't find a confidence interval of the difference, instead I assume the CI of the ratio is listed. My guess is that I interpret to have bioequivalence if the value of the Ratio[% Ref] is included in the CI_90Lower and CI_90_upper. Is this right?
4) I am not clear if the 95% confidence level from the "Bioequivalence Fixed Effects" window of the BE wizard is related to the 90% confidence interval from the "Bioequivalence Options" window.

I'll stop here, thank you in advance for your patience.