Bioequivalence and Bioavailability Forum

Dear all,

I am still wondering about the Danish policy for BE, so I got curious and wanted to see some power curves for 2,2,2-BE studies when 1.0 must be part of the 90% CI. The data I have are based on a brute force metho, i.e. the calculated power asymptotically approaches the true power as the number of iterations/resmaples approach infinity.

So, here an example, using R lingo, where N is the number of sbj in each sequence, Pwr1 is power according to the Danish requirements, and Pwr2 is power with the usual requirements. CV was 28%, R/T was 95%, 120000 resamples used:

N=c(16, 20, 24, 28, 32, 36, 40, 44, 48, 50, 60, 70, 80, 90, 100, 110)
Pwr1=c(0.712, 0.751, 0.754, 0.738, 0.718, 0.696, 0.677, 0.654, 0.637, 0.629, 0.581, 0.535, 0.493, 0.451, 0.415, 0.38)
Pwr0=c(0.772, 0.856, 0.911, 0.946, 0.967, 0.98, 0.989, 0.993, 0.996, 0.997, 0.999, 1, 1, 1, 1, 1)

Example how to read: If we have 16 sbj in each sequence then the power with the standard requirements is approximately 77.2% (Fartssie gives 77.6% on my machine); with the Danish requirements it is approximately 71.2%.

These data are rather shocking to me, provided they are true. The power has a maximum in the early 20'ies at about 75%. So if a company believes their product has a CV of 28% and T/R=95% then there is no way of powering the study to 80%.

So my questions: Are these data correct - could somemone with more specialised software check those values? I think the assumed CV and R/T values are reasonable, agreed? Did anyone ever understand the Danish thinking? Talk to a regulator there perhaps?

Best regards
EM.



*: What's the real power at CV=65%, R/T=95%, 38 sbj (19 in each seq)??