Bioequivalence and Bioavailability Forum

Dear drsinghs,

❝ To be more precise I will share a hypothetical case - if 2 waycrossver study is already completed and observed T/R ratio is 115 for Cmax and 125 for AUCt with > 30% intraCV for Cmax and > 45% for AUCt, Can I expect successful results if I go for replicate design?

Big risk.

If the CV for AUC is bigger than CV for Cmax then there is a risk the study will be flagged for inspection by some authorities, especially FDA. It is often a sign of something having gone badly wrong, and is generally not lending the data much credibility.
Second, I know of IECs/IRBs now beginnng to understand that power and statistics and sample size are not just academic issues but need to be dealt with practically. It may be a seriously uphill struggle to dimension a study with a T/R of 125% (AUC) - try and calculate the sample size for 80% power, 125% T/R and 45% CV.
Your only practical chance is to assume T/R being much closer to 100%. Then you can at least arrive at fairly reasonable sample size, but on the other hand that implies that you disregard the data from the first study. You generally need a very good and justified reason to do so.
I would either say it is game over with the current formulation or suggest to try very hard with audits and internal reviews in order to figure out if something went wrong before proceeding.

The consideration above is regardless of replicate design or no repliacte design.