Bioequivalence and Bioavailability Forum

Hi Lucas,

yep, combos can be challenging when it comes to the blood volume. What I have seen is to optimize the sampling schedule for each drug and split samples accordingly. Drawbacks:

• Makes only sense if the PK is substantially different.
  
• The logistics is challenging. We color-coded all vials and even the respective rows in the CRF. Turned out to be not fail-safe.
  
• I have never seen something like this for more than two drugs.

❝ is it possible to not use the replicated samples for the other 2 drugs and apply conventional ABE for them, and consider the replication only for the HVD?

Not sure whether I understand you. Can you post sequences / periods you have in mind?

❝ Other option would be to use Balaam's 4x2 design, but I don't think that someone has budget for that...

Correct. In Balaam’s design we throw away half of the sample size in the estimation of T/R. Furthermore, I don’t know how to estimate the sample size. RT|TR|RR|TT is currently not implemented in PowerTOST sampleN.scABEL().