Bioequivalence and Bioavailability Forum

Dear Manu,

❝ I'm new on this forum perhaps my question has already been discussed in another topic...

Welcome to the club.

❝ Anyway, I'm trying to compute sample size for a BE study with HVD, considering a replicate 3-period design (RTR/TRR/RRT) with SABE, as suggested by FDA.

❝ Is there any existing R macro (or SAS..let's dream ;) that has been developped to compute sample size?

To my knowledge there is no piece of software out there which could be used to accomplish that task. Not in R and even less in SAS .

To cite the two Laszlo's [1] to see why:
"Overall, the statistical properties of the methods proposed by EMA and FDA are rather complex as a result of the additional conditions and requirements (mixed procedure, GMR constraint, and (for EMA) a cap on the limits). Furthermore, the tests required by both EMA and FDA are dependent on each other which makes the theoretical treatment very complicated. Therefore, the required sample sizes were obtained by simulations."

Implementation of simulations to obtain the power and subsequent the sample size may be a not so easy task. Not to consider the run time of such an sample size estimation.

Thus at the moment you only have the opportunity to use the sample size tables given in the reference. They cover the full replicate design (2-sequence-4-period) as well as the partial replicate design (3-sequence-3-period), the EMA suggested analysis using widened acceptance limits as well as the FDA recommended method via a 95% CI of the SABE criterion.

See this thread for some further discussions we had here.

BTW: There is software out there for sample size estimation in the context of ABE which can handle more replicate designs than 2x2m. Search the forum for PowerTOST .

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[1] Laszlo Endrenyi, Laszlo Tóthfalusi
Sample Sizes for Designing Bioequivalence Studies for Highly Variable Drugs
J Pharm Pharmaceut Sci 15(1), 73–84 (2011)