Bioequivalence and Bioavailability Forum

Hi zizou,

❝ Nevertheless in practice power is almost equal to 0.05 at GMR 0.8000 (if you replace axis "sample size" by "CV" in the figure and the points (for each CV) will be calculated as for minimum required sample size, the curve with power 0.05 (almost straight line) will be approximately at GMR 0.80).

Correct. Your wish is my command. For every CV/GMR-combo the sample size estimated for expected GMR 0.95, target power 80%:

❝ So alpha could be seen as less than 0.05 (with two decimals accuracy) only in pilot studies or in really underpowered studies. (If I am not mistaken.)

Correct.

❝ To the slide, the figure is for classical 2x2 design?

Yep.

❝ It seems strange to me, especially curve alpha=0.0500, which is raising and I'm not getting why it's descreasing with n>56. Try recalculation at n=60, CV=35% (last minor tick) ... with GMR 0.80, the power will be 0.0500 (so this point should be under the curve 0.0500 and not above) or am I wrong somewhere?

No, you aren’t (see below).

❝ Maybe I am just not understanding the slide without the comments presented in Barcelona.

The context were two-stage designs. Since I started to present TIE-contours in 2012 attendees were worried about the ‘large red area’ in ‘Type 2’ TSDs (Method C, D,…) and TIEs close to 0.05 for low to moderate CVs. In the same presentation compare slide 16 (‘Type 1’ – Method B) with slide 23 (‘Type 2’ – Method C). In the former we get small TIEs caused by the fraction of studies which stop in the first stage (BE or not) evaluated with α 0.0294, whereas in the latter the evaluation might be done with α 0.05.
Since in TSDs the TIE is based on simulations and R’s filled.contour() uses the raw data, the plots looked awful. Therefore, I opted for thin plate splines (package fields) to smooth the data. Unfortunately when I decided to show the 2×2×2 fixed sample design as well I was lazy and used the same code (although no smoothing is required). Hence, the shape of contours at the extremes are an artifact. My fault.