LLOQ ≤5% of expected or observed Cmax? [Bioanalytics]

posted by Helmut Homepage – Vienna, Austria, 2018-10-18 12:28 (740 d 08:35 ago) – Posting: # 19468
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Hi Beholder,

first of all congratulations for mastering the forum’s tricky syntax of nested lists. ;-)

» […] I have revealed that EEU BEQ GL has interesting note in validation chapter which is not presented in EU BEQ GL, namely:
» “[…] The LLOQ cannot be higher than 5% of Cmax (the minimum Cmax value from the entire sample of subjects) ).”

AFAIK, the Russian language leaves a lot of space for interpretation. Is the common meaning of »не должен« really equivalent to “cannot” or “must not”? Since I don’t speak Russian, I have to rely on A(un)I: Google, Yandex, and Bing translate it as “should not” – which is exactly the phrase used in the EMA’s GL.

If it is mandatory (your #1), very stupid. #2 is a show-stopper.

I can only tell you what is done in studies for the EMA. Use an estimate of the lowest expected Cmax and base the LLOQ on it. Depending on the expected variability CROs commonly opt for 2% or even 1% of the average Cmax. Nerds like me work with modeling, stuff like that (replace t½ with Cmax), or simulations. Of course, if individual data are available (pilot or other studies), better. Never saw revalidation. If you are cautious, exclude the subject. If that doesn’t occur too often, the loss in power is small.

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Helmut Schütz
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