Bioequivalence and Bioavailability Forum

Dear Imran!

❝ Boltan gives a example to calculate sample size (page no. 157) where it estimate sample size using the mean and SD.

Be careful! To quote Bolton/Bon:

“Estimates of the standard deviations of the ratios of the values of each of the parameters […] were determined from a small pilot study.”

If you don’t have the study’s data available, where to you get the SD of the individual ratios from?

I used subjects 1-6 of my example data to get:
SD of T/R-ratios: 0.19923581
applying Eq.(6.6) with a maximum deviation (Delta) to detect of 0.2 one gets N=9.71
which is in agreement with the common method based on CV%-intra, where N=10 is estimated for a point estimate of 0.95 (Delta 0.05).
With a PE of 0.90 N is estimated with 18…

Using subjects 7-12 (6.6) gets N=23.9, again in agreement with the CV%-intra method, which gets N=24.

❝ so calcualtion of a sample size using this formula will be questionalbe!!!!

Hmm, I agree, but since you need to have access to raw data for Bolton/Bon’s formula also, why not using one of the ‘traditional’ sample size estimations based on the intra-subject CV anyway?
It looks like that (6.6) gives the ‘correct’ sample size for a PE of 0.95; but other Deltas should be possible according to the Guidelines…