Bioequivalence and Bioavailability Forum

Hi everybody and nobody!

❝ I agree with ElMaestro. If you design a replicate study based on the CV_w of a 2×2×2 crossover you have to assume that CV_wT = CV_wR.

Practically I agree with everyone of you.
Nevertheless I have one nitpicker's question.
We have to assume CV_wT = CV_wR = CV_w? (If we design a replicate study for EMA based on the CV_w of a 2×2×2 crossover.)
Or CV_w can't differ when CV_wT = CV_wR?
Theoretically I can imagine (no real) data of 2x2x4 replicate study - see following idea:
After Test treatment we will have almost the same values for each individual subject (e.g. subject No. 1 value 0.9501 after the first T and 0.9502 after the second T (before ln-transformation)) - for simplicity geometric mean of T values close to 0.95.
In the same way after Reference treatment we will have almost the same values for each individual subject (e.g. subject No. 1 value (1/0.9501) after the first R and (1/0.9502) after the second R (before ln-transformation) - If all the values of R are reciprocal values of T we should get the same intra-subject CV for T and R.) - for simplicity geometric mean of R values equal to (1/0.95).
So GMR T/R of all "pooled" data will be close to 0.95/(1/0.95)=0.95^2=0.9025 and CV_w used for CI calculation will be higher than CV_wT and CV_wR?
I know, in this kind of example the CV_wT and CV_wR are extremely low, but the point is that theoretically the CV_w observed in 2x2 study can be higher than 30% (so we can try replicate design with possible widening of BE acceptance criteria) but the CV_wT and CV_wR (which we don't know from 2x2) can be lower.
Fact or Fiction?

Best regards,
zizou