Bioequivalence and Bioavailability Forum

Hi Mauricio,

❝ I am looking for a post in this forum that explain what is the best design to replicate a bioequivalence study.

Maybe there is one but the search function is slow those days. The data base seems to be corrupted and I didn’t have the time to repair it yet.

❝ The 4x4 or 4x2? Normally, I use 4x4 this is a best choice? Or I can use 4x2 with same eficcacy?

To clarify: By 4×2 do you mean RTRT|TRTR and by 4×4 RTRT|TRTR|RRTT|TTRR or yet another one (e.g., TRRT|RTTR|TTRR|RRTT)? The notation used by PowerTOST is treatments × sequences × periods.

library(PowerTOST)
print(as.data.frame(known.designs()[8:9, ]), row.names=FALSE)

 no design    df df2 steps bk bknif   bkni                      name
  6  2x2x4 3*n-4 n-2     2  1   1/4 0.2500 2x2x4 replicate crossover
  7  2x4x4 3*n-4 n-4     4  1  1/16 0.0625 2x4x4 replicate crossover

Since both have the same degrees of freedom they should have the same efficacy.

But: IIRC, in the late 1990 Donald Schuirmann argued against more than two sequences in full replicate designs. See also Appendix B of the FDA’s guidance.