Bioequivalence and Bioavailability Forum

Hi myy,

❝ The dissolution profiles have already revealed a tendency of slower dissolution rates of the test formulation although statistically from the f2 values similarity was concluded.

Unfortunately in vivo sometimes does not match in vitro.

❝ Since the test product fails to meet only the lower end of the criteria for AUC 0-t it is not truely bioinequivalent. Could it be possible that bioinequivalence was demonstrated accidentally although the two products are actually bioequivalent? How could this be proven?

Don’t worry, it is too late. SCNR.
I’m not a friend of a posteriori power, but even C_max passed by luck. With your ratios and CVs power is just 32.2% for C_max and 14.6% for AUC.

❝ In the study protocol I have read: “A formal statistical calculation of the study’s power was not carried out (given the scarce literature on intraindividual variability and confidence intervals for ivermectin).” Is it therefore really only possible to guess the sample size?

Well, to perform a study “out of the blue” is against the BE-GL Section 4.1.3 (“appropriate sample size calculation”) and ICH-E9. It is surprising that both the IEC and the regulatory authority (may I ask which one?) approved the protocol. If the CV is unknown, you should have performed a pilot study.

❝ Would it be advisable to perform another bioequivalence study with the same design?

No. If I take your ratio and CV for AUC as “carved from stone” (cave: there is no guarantee that you will be able to get exactly these numbers in the new study) you would need 232 (!) subjects to show BE with 80% power.