Andreas,
There are many ways to create a VPC (come to PAGE this year and hear
about them from Mats Karlsson and myself).
In the specific case of using a VPC to simulate both the between
subject variability and the residual unidentified variability for
comparison with the observations then I would apply the same truncation
rules used to create the model. If you have a LLOQ defined and you are
in the unfortunate situation of not being able to use values less than
LLOQ then I would suggest you truncate the simulations.
If you have honestly reported measurements (i.e. without omitting
measurements less than LLOQ) then I would not truncate the simulated
values -- I would even accept negative simulated values because if your
residual error model was correct then there would be negative measured
values.
Best wishes,
Nick
andreas lindauer wrote:
Dear NMusers,
I have a question regarding simulations for a VPC. When a combined
residual error is used it happens that for low concentrations negative
values are simulated. While this is statistically correct, I wonder if
it is correct to use these results for the VPC because the
distribution of the observed low concentrations is truncated by the
LLOQ. So the VPC might suggest model misspecification for lower
concentrations. Further, when one wants to use the model for clinical
trial simulation should then the negative (BQL) values be omitted
because they would never appear in reality?
I would like to know how the more experienced NMusers handle this.
Thanks in advance, Andreas.
____________________________
Andreas Lindauer
University of Bonn
Department of Clinical Pharmacy
An der Immenburg 4
D-53121 Bonn
phone:+49 228 73 5781
fax: +49 228 73 9757
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford
