Bioequivalence and Bioavailability Forum

Dear all,

I’m wondering what we can say about the precision of estimated CV_WR in different replicate designs. One full replicate (TRTR|RTRT) and the partial replicate (TRR|RTR|RRT) are mentioned by both the FDA and the EMA. An alternative full replicate, but requiring only three periods was used by the Lászlós in 2009 and is also mentioned in the new Russian draft GL, namely TRT|RTR. On the contrary to the partial replicate we could also derive CV_WT. For CV 30%, T/R 95%, 80% target power I get n=20 for the 4-period design and n=30 for both 3-period designs with power of 82.02% in all designs. So far so good. What about the precision of the estimated CV_WR? Let’s look from how many subjects the value is estimated:
TRTR|RTRT:   20 (100%)
TRR|RTR|RRT: 30 (100%)
TRT|RTR:     15 (50%)
Heretic question: From TRT|RTR the estimate will be less precise (only half of the subjects used), but we get additional information about the test. Less chance of outliers? Duno.