More samples – less variability (for Cmax) [Design Issues]
❝ 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 tmax since a reliable estimation of λz is no more needed.
Would be fun to simulate that. Makes a nice paper.
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Helmut Schütz
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Science Quotes
Complete thread:
- More samples – less variability (for Cmax)? nobody 2017-05-23 09:07 [Design Issues]
- More samples – less variability (for Cmax)Helmut 2017-05-23 12:56
- Sample volume Ohlbe 2017-05-23 14:14
- Sample volume nobody 2017-05-23 14:50
- Sample volume Ohlbe 2017-05-23 19:00
- Sample volume nobody 2017-05-23 14:50
- More samples – less variability (for Cmax) nobody 2017-05-23 14:31
- Sample volume Ohlbe 2017-05-23 14:14
- More samples – less variability (for Cmax)Helmut 2017-05-23 12:56