Back to the Top
1) has anyone legitimately used zero as a standard point in a Glp or clia assay?
2) if you give a therapeutic drug, and assay drug or target in non responders isn't that activity
therapeutic drug monitoring?
Back to the Top
Dear Ed:
What do you mean by "legitimately"? I would hope so always. The whole idea of using CV% as a
measure of assay precision is badly flawed. For openers, you might look at
Jelliffe RW, Schumitzky A, Van Guilder M, Liu M, Hu L, Maire P, Gomis P, Barbaut X, and Tahani B:
Individualizing Drug Dosage Regimens: Roles of Population Pharmacokinetic and Dynamic Models,
Bayesian Fitting, and Adaptive Control. Therapeutic Drug Monitoring, 15: 380-393, 1993.
There is a section in there which deals with this issue. A more recent submission on this idea
was rapidly rejected by Clinical Chemistry without any objection to its scientific content, but
simply that it "lacked interest to the lab community and was "mathematical". How is such a "head in
the sand " attitude "legitimate"?
For the present, I would encourage everyone to read the above article and to ask themselves what
the word "legitimate" means in any scientific discussion.
Best regards to all,
Roger Jelliffe
Roger W. Jelliffe, M.D., F.C.P., F.A.A.C.P.
Professor of Medicine Emeritus,
Founder and Director Emeritus
Laboratory of Applied Pharmacokinetics
USC School of Medicine
Consultant in Infectious Diseases,
Children’s Hospital of Los Angeles
4650 Sunset Blvd, MS 51
Los Angeles CA 90027
Back to the Top
For a simple application zero cannot be presented as such on a log scale. What is the log of zero
to enter? To get around this a number approaching Zero but not actually zero is used.
Mathematically is it appropriate to represent zero as .0001 or .00001 etc, etc, etc.? Zeroes or
blank samples are used to "blank" instruments and adjust instrument responses but it is another
thing to enter zero as a standard point.
--
Thanks Roger. I believe I have to be on your side on this. That is, I would like to see a sound
argument on the application or rejection of zero as a standard point. Both sides not only arguments
supporting the exclusion of zero but those supporting inclusion as well.
Current FDA guidance does not specifically proscribe the use of a zero as an anchor point. That
guidance does describe ... Non zero standards. But anchor points can be used on either side of the
calibrator. The EMA does specifically state that blanks or zero point should not be used.
Back to the Top
Thank you, Ed. I do not understand why one has to consider using a log scale. Why is that? Zero is
zero, and a blank is a blank, measured with an SD that is easily determined.
All the best,
Roger
Back to the Top
Ed,
> Roger Jelliffe
> Thank you, Ed. I do not understand why one has to consider using a log scale. Why is that? Zero is
> zero, and a blank is a
> blank, measured with an SD that is easily determined.
>
All the best,
Roger
I agree with Roger's wise comment.
Can you give us a scientific (not regulatory guidelines) answer to these questions :
1. Why do you need to use a log scale?
2. Why can't you measure concentrations in a set of blanks (true conc is zero) and calculate the
average and standard deviation of the set of measurements?
|
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@lists.ucdenver.edu with "Zero as a Standard Point" as the subject |
Copyright 1995-2014 David W. A. Bourne (david@boomer.org)