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I was hoping someone could clear up a couple of issues in regard to
reporting routine sample analysis to the FDA from the guideline
"Bioanalytical Method Validation."
When calculating inter-assay precision (%CV) at each QC level from a
number of analytical runs, should each duplicate QC value be included
in the calculation or should an average of the two values represent
the data point for for use in the %CV calculation?
And, when an analytical method is used across a number of clinical
trials, should inter-assay accuracy and precision calculations be
made for each clinical trial or across all trials in which that
method was used?
Thanks for your help,
James R. Evans
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The following message was posted to: PharmPK
Hi James,
Really the data from all QC samples (separately at each
concentration) should be used in an ANOVA or linear mixed-effects
modelling type approach - with Day and Replicate number as factors.
This then prevents any form of "falsely low" estimation of between-
assay precision due to the contribution of within-assay variability
as some (50% if using only duplicates each day) of the data are
replicates within a day....this approach also allows one to estimate
the within- and between- day variability in the one analysis in a
much more statistically valid way than the approach "typically"
used. Meaning the replicates wont help with this the poor estimation
of between-assay variability and also throws away the ability to get
intra-assay variability...
Hope this helps,
David
David Foster, PhD
NHMRC Research Officer
Department of Clinical and Experimental Pharmacology
Faculty of Health Sciences
The University of Adelaide
Adelaide, South Australia 5005
Tel: +61 08 8303 5985
Fax: +61 08 8224 0685
Email: david.foster.-a-.adelaide.edu.au
http://www.adelaide.edu.au/health/pharm/
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Do you also include the QC samples which fail the acceptance criteria
(85 to 115 % vs nominal value) in the calculation of assay variability?
Thank you,
Charina
Charina P. De Silva, Ph.D.
Bioanalytical R&D, United Laboratories, Inc.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)