Bioequivalence and Bioavailability Forum

Hi nobody,

❝ Lately I recognize a trend to increase number of samples in study designs for BE-studies to considerably more than 20 per application even for "simple" IR formulations.

❝ First thought: $$$$ (CRO designs study )

Always correct but I think it’s more this one:

❝ Second thought: Might there be a lower variability e.g. for Cmax with increased number of samples around Cmax (effect on AUC will be lower, in the absence of secondary peaks, I guess)? Gut feeling tells me: Possible. But to a relevant extent? Does increase in number of samples from about 16 (oldschool) to far beyond 20 really buy something regarding "quality" of data?

Makes sense. See this oldie.

❝ Isn't there an ethical/practical limit for blood sampling (from the top of my head I remember an absolute limit for blood volume to be taken within a trial...)?

Yes there is. The total volume in the study should not exceed the one of a blood donation (if unavoidable, longer washout, measurement of HCT before later administrations, eventual exclusion of subjects…). But in the old days 10 mL / sample were taken and nowadays 5 mL are common. Still not an issue even for replicate designs. For really extensive sampling (i.e., gastric resistant formulations) 4-period replicate designs are problematic and 3-period replicates might be the only way out.

Since for the EMA AUC₇₂ is acceptable for all IR products, in my studies I shift sampling towards the expected t_max since a reliable estimation of λ_z is no more needed.

Would be fun to simulate that. Makes a nice paper.