Bioequivalence and Bioavailability Forum

Dear Helmut,

❝ Amazing. Small is beautiful?

For me your finding is not so astonishing.
Remember one of the features of the scaled ABE method: In its pure form the power is independent of the intra-subject variability, at least if we assume a true ratio T/R of ~1. Therefore the FDA had discussed about a fixed sample size (24 or 36) for such studies.

The simplification of the scaled ABEL method and the additionally regulatory constraints like cap on widening the acceptance ranges or the PE constraints of course change that behaviour. But as your numbers show not to that extent that you observe a benefit for larger pilots.

I would nevertheless not state "Small is beautiful". This would only be the case if you take only the variability from the pilot. The other side of the moon is the PE and its value may be very misleading in small pilots, especially if we talk HVD.