Bioequivalence and Bioavailability Forum

Hi Astea,

❝ I am very grateful for your detailed answer!

And I’m grateful for interesting questions! (see my signature)

❝ ❝ Whenever you assume a CV_wR keep the (maybe counterintuitive) behavior of power in ABEL in mind.

❝

❝ Are there some general sound advices how to plan the study with SCABE?

By counterintuitive I meant power curves for different CVs (while keeping the the T/R-ratio and sample size constant) in ABEL. In ABE it is straightforward: Higher CV → wider CI → lower power → increase the sample size to keep power. Hence, if you want to be on the safe side, assume a higher CV (or the upper CL of an estimated CV). I will explore your example for ABEL below.

❝ As an example, on the basis of literature data CV of some drug ranges from 32 % to 46 %. If we plan sample size basing on the highest value we would get the less number!

Let’s assume CV 32%, T/R 0.9, target power 80%, 4-period full replicate for the EMA’s ABEL:

If the CV decreases, power increases. That’s similar to ABE. But if the CV increases, power increases as well because the acceptance range will be wider and a smaller sample size would be sufficient (yes, you are right!). This increase ends at 50% because the scaling ends here. Any higher CV will decrease power again. Starting here, ABEL – apart from the additional PE-restriction – behaves like ABE.

Now let’s assume CV 46%:

With lower CVs we will loose power for the given sample size. Whether such a loss is acceptable is another story (at 32%: 73.5%).

❝ What should we prefer?

I would say for any CV the rule for ABE given above reverses: If you want to be on the safe side, assume a lower CV (or the lower CL of an estimated CV). If you have good reasons that the CV will not drop much below 50%, use the ABE-rule again.