Bioequivalence and Bioavailability Forum

Dear Mittyri,

❝ Labs have NOT been used to having their data FITTED using modern quantitative modeling methods which require one to evaluate credibility of a measurement correctly. That is the problem. Labs have been used to CV% only. CV% is simply not suitable for today’s modern quantitative modeling methods.

❝ They invent the LLOQ. LLOQ is their ILLUSION!

❝ NO NEED for this!

❝ [So need to know, or have a good estimate, of the SD of every serum level.

❝ Labs always get SD anyway, to get the CV%.

❝ Then, Var = SD²

Mmmm. It is true that bioanalysts don't know how their data will be processed later. And they just don't care.

But PK scientists should also realise that the SD is not in any way a constant feature of a bioanalytical method. It can vary over time. From one run to the next (ion source getting dirty, sleepy or sloppy analyst etc.). And from one instrument to the next, should you have several involved in your study.

Not only that: precision is just one of the problems. Accuracy is another. Where does it come into Roger's picture ? The LLOQ is the lowest concentration you can measure with an acceptable precision and accuracy. Problem is, you can't really have a reliable estimate of accuracy below the LLOQ.

Question: where do you get your SD from ? Within-run ? Between-run ? Most importantly, from how many replicates ? In his response Helmut mentions SD calculated from 2 or 3 replicates. Sorry Helmut, but I would consider any such value as meaningless. To me, that would be the same thing as running a t-test or Chi-square on 5 values.

❝ My question is are there any steps forward in that direction?

Looking at the draft M10 guidance: nope.