NONMEM Users Network Archive

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RE: Honest measurements

From: Ed O'Connor <efoconnor>
Date: Mon, 24 Aug 2009 08:36:06 -0400

Sense and nonsense.

Analysts are constrained certainly but good analytical science is good
analytical science. During the method development stage several parameters
are examined.

One parameter for example is recovery of analyte from a set of spiked
individual (matrices). Another exercise is the recovery of material from
spiked matrix after exposure to a number of stability challenging
conditions, e.g., freeze thaw. During these tests it is certainly possible
to "find less or, even "none" of the response(s) to the analyte(s).

Analysts would then "improve" the assay using a number of techniques
including the addition of preservatives or specifying the handling and
storage conditions. Too often however, the clinical collection parameters
may have been defined before the conclusion or event the start of analytical
method development and perhaps "if pushed too far and incessantly" the
analyst will release "nonsense data" or instrument responses free of
"interpretation".

For people at the next rung to use data this in any rational way suggests
that those people should perhaps be using a seer rather than an analyst.
When they are stung by the results of their data analysis, they will
immediately revert and "blame" the analyst (or if they do not, regulatory
agencies will) for releasing "bad" data.

PK/PD and Analytical scientists usually work together during the analytical
process. PK/PD driving with LLOQ, suggesting metabolites, Analytical
providing the best approach to meet that requirement including meeting all
current method validation and reporting guidelines.


Edward F. O'Connor, PhD
78 Marbern Drive
Suffield, CT 06078
 
Tel 860-668=6201
Cel 860-324-6780
efoconnor

Edward F. O'Connor, PhD
78 Marbern Drive
Suffield, CT 06078
 
Tel 860-668=6201
Cel 860-324-6780
efoconnor

-----Original Message-----
From: owner-nmusers
Behalf Of Stephen Duffull
Sent: Monday, August 24, 2009 4:18 AM
To: Nick Holford; nmusers
Subject: RE: [NMusers] Honest measurements

Mats

I agree with Nick. Negative "observed" concns do occur for assays, even in
my limited time working with HPLC I have seen them, however due to LOD/LOQ
they are never really looked for and certainly never reported...

Steve

> -----Original Message-----
> From: owner-nmusers
> nmusers
> Sent: Monday, 24 August 2009 6:25 p.m.
> To: nmusers
> Subject: [NMusers] Honest measurements
>
>
>
> Mats Karlsson wrote:
>
> << Chemists, however pushed, would never report negative
> concentrations, not
> for past studies, not for future studies. The methods they use don't
> even
> report them.>>
>
> I am working with a chemist using LC/MS who has been persuaded to look
> honestly at his data without preconceived ideas of limits of
> quantitation and detection. Indeed when he opened his eyes he found
> that his system was indeed giving negative concentration measurements
> (at times when concentrations were expected to be very low).
>
> Of course we must do other things when the data is censored by bad
> scientific practice in the chemist's lab but with honest measurments an
> additive residual error model is required.
>
> Nick
>
>
> --
> Nick Holford, Professor Clinical Pharmacology
> Dept Pharmacology & Clinical Pharmacology
> University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
> Zealand
> n.holford
> mobile: +64 21 46 23 53
> http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

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