Handling BLOQ values (Fisher Info etc.) [Bioanalytics]

posted by Helmut Homepage – Vienna, Austria, 2019-03-16 14:39  – Posting: # 20039
Views: 1,884

Hi Mittyri,

» some time ago I was pleased to be invited on the session with Roger Jelliffe.

Congratulations! Roger is a guy of strong opinions.
When David Bourne’s PK/PD-List was still active, Roger regularly ranted about the LLOQ (examples). In PK modeling nobody simply ignores BLOQs. We still have no method dealing with “BQLs” in NCA (Martin :waving:).
Essentially Roger is absolutely right (speaking also from my background in analytical chemistry).

[image]BTW, on a similar note the best weighting scheme in calibration is 1/s2 – and not 1/x, 1/x2, 1/y, 1/y2. They are all arbitrary and lack any justification. OK, in between those lines of the EMA’s BMV guideline …

A relationship which can simply and adequately describe the response of the instrument with regard to the concentration of analyte should be applied.

… it seems that it is recommended not only to assess calibration functions themselves (chromatography: linear, quadratic, …; LBA: 4-, 5-parameter logistic, …) but also different weighting schemes (based on the back-calculated concentrations’ accuracy & precision). Rarely done. :-(
Of course, 1/s2 requires at least duplicates (even after rejecting a measurement). In our lab we had this procedure: Validate the method with 1/s2 and also the weighting scheme which gave the 2nd best outcome. Sometimes sponsors didn’t like triplicate standards (money, money). Then – if we ended up with a singlet – we switched to the other weighting scheme. Regulators didn’t like that (“subjects are not treated equally”).

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

I strongly doubt it.

» Even in analytical methodology (say QC samples): isn't possible to handle that values (as they are) for example for the mean evaluation for some level of QC sample?

Not sure what you mean here.

Helmut Schütz

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