Bioequivalence and Bioavailability Forum

❝ Dear Helmut:

       ↑↑↑↑↑↑ Not interested in the opinion of other members?

❝ Can we use 10% formulation difference or more for sample size estimate.

Sure.

❝ I have a failed BE study and now we want to plan another BE study with the sample size based on the mean ratio (T/R)=112% (from the failed BE study). Is it appropriate to consider this much difference.

Of course, it is. The estimate you got from your own study is better than any assumption you might have used in planning it. However, power – and thus, the sample size – is extremely sensitive to the T/R-ratio (see the examples in this article). It would be risky to assume that in the next study the T/R-ratio will be exactly 112% again. Some statisticians call that the Carved-in-Stone approach. If it deviates even more from 100% you might fail again! On the other hand, if it is ‘better’ you invested more but have an even higher chance of passing than planned.

Don’t follow guidelines blindly (even if from the FDA).