Bioequivalence and Bioavailability Forum

Many Thanks Helmut;
It was a non-replicated study design. We are considering RSABE according to the recent FDA presentations and papers. The full replicate design is indeed what I favor.
I did a sample size calculation for the non replicate design (usual cross over design) using the Excel spreadsheet FARTSIE from David Dubins, I have found this spreadsheet to be most useful in the past. Using a desired power of 0.9, with CV of 30.05 and an anticipated ratio of 0.93. I get 67 subjects and this is more than your estimate. I wonder why?
{I must try the freeware package you recommend}. I do have a Study Size program from Sweden, but have not used it for this project as yet. It seems to be an excellent program. Update using Study Size for the above sample size calculation again I get 67 subjects.
There is a reference I have found that appears to be most useful since it tabulates the simulations for sample size including the EMEA and FDA’s approach to highly variable drugs.
Sample Sizes for Designing Bioequivalence Studies for Highly Variable Drugs
Laszlo Tothfalusi¹ and Laszlo Endrenyi²
1 Semmelweis University, Department of Pharmacodynamics, Budapest, Hungary.
2 University of Toronto, Department of Pharmacology and Toxicology, Toronto, ON, Canada, J Pharm Pharmaceut Sci (www.cspsCanada.org) 15(1) 73 - 84, 2012
When I consult this paper I see for the fully replicate design with 4 periods that for CV of 30% and power 0.9 with GMR ratio of 0.9 that 38 subjects are estimated.
So I am thinking ~ 40 subjects is needed. Any thought are welcome,

Angus