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Hello everyone,
We are having some issues with a sponsor which want to report no
detected peak as BLOQ instead of 0.0 since he says that it is
interfering with the pK analysis of the data.
I'm seeking your experience as how do you report no peak observed in
the pre-dose or any other sampling time point?
The other concern I have, is if we report no detectable peak as BLOQ,
how can we confirm that the blank check is free of possible
interference if we can not report as 0.0 but BLOQ?
Any comments/ remarks/observations are welcome
Thank you,
Sylvain
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The following message was posted to: PharmPK
Hi Sylvain,
In my opinion, you never can report concentrations of zero; this has no
meaning because it depends on the detection limit of your analytical
method. We always report all samples with concentrations below LOQ as
BLOQ. The only other way is to use BLOD.
Kind regards Bert
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The following message was posted to: PharmPK
What really is the difference? If a peak is not reported is the sample
not LLOQ? Can you really claim 0.0? I do not believe you can with any
certainty. That is why LOD is only used to determine where the LLOQ
must be set to limit risk. LOD will vary from day to day but the LLOQ
is fixed. I would side with the SPONSOR and call thison your SOPs and the protocol you may have three designations 1) but above LOD, 2) collapse into the simple an NP would be such as instrument response could be reported out for the sample but the
concentration reported would be
Ed O'Connor, PhD
Technical Director, Immunoanalytical
Tandem Laboratories
115 Silvia Street
West Trenton, New Jersey
609-228-0243
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Dear Bert:
Why do you use BLOQ or BLOD at all? Look in any statistics
book. What is a quantitative measure of the credibility of a data
point? I have NEVER found a CV% or a BLOQ or BLOD. It is the Fisher
information of a data point, the reciprocal of the variance with
which the point was measured. Once again, here is more material below
on this point.
Date: Tue, 23 Jan 2007 16:01:20 -0800
From: Roger Jelliffe
Subject: PharmPK Re: LLOQ and LLOD Illusions
Dear PharmPK colleagues;
Once again, I would strongly encourage you to get off the CV
% and the illusion of the LLOQ and LLOD. I would strongly encourage
you all to go to ANY statistics book and examine what it says about
measures of credibility of a data point. I have NEVER found the CV%
referred to as such a measure. Instead, they talk about the Fisher
information of a data point. I have said more (below) on previous
occasions. PLEASE go to a statistics book and look at measures of
error and credibility. The whole idea of LLOQ and LLOD is an illusion
developed by the analytical lab community, (and by no one else I know
in the overall scientific community), probably because it is less
variable than the SD. However, it is NOT science or even good
statistics. Please read again what is below.
Very best regards,
Roger Jelliffe
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The following message was posted to: PharmPK
Dear Roger,
With regards to LLOQ and CV%, you're probably right from a scientific
standpoint.
However as long as the guidelines (e.g. FDA, Guidance for Industry,
Bioanalytical Method Validation, May 2001) refer to these concepts
it's wise to implement them in your regulatory studies.
Best regards,
Kees
Kees Bol, Ph.D.
Kinesis Pharma BV
www.kinesis-pharma.com
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The following message was posted to: PharmPK
Dear All
It is really frustrating to come to the conclusion that, in Kees'
words, "as long as the guidelines refer to these concepts" they ought
to be implemented. In my humble opinion, what drives scientific
advancement is good science from which, usually after some time,
guidelines are generated, and not the other way around. We can all
remember endless historical instances when purely by peer pressure
and indisputable rationale guidelines have been revisited and
improved for the benefit of us all. Fortunately nowadays regulatory
agencies are even better prepared, and open minded, for this task. A
guidance is not a stone carved law, and every submitted study should
bring forward its own scientifically based rationale, perhaps rather
than a series of reference notes to the applicable guidelines blindly
and uncritically accepted. Roger's patient and well substantiated
advices, seconded by so many of us, are indeed nothing new. I
strongly support Nick's suggestion for people to remember basic
statistics or hook up with a biostatistician. Maybe then the
guidelines will just naturally end up being updated.
Regards
Luis
--
Luis M. Pereira, Ph.D.
Assistant Professor, Biopharmaceutics and Pharmacokinetics
Massachusetts College of Pharmacy and Health Sciences
179 Longwood Ave, Boston, MA 02115
Phone: (617) 732-2905
Fax: (617) 732-2228
Luis.Pereira.-a-.bos.mcphs.edu
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