Dear all,
I have a big problem understanding some simulation results and hope that
somebody can shed some light on what is happening.
I have simulated a PK study using a previously developed PopPK model (very
standard, 3-cmt model with some IIV and also inter-occasion variability on KA
and F1). I wanted to use the model to design a new PK study. The aim of the new
study design would be to be able to reliably estimate CL, V2, KA, and F1 when
combining the data set with the data that is already available. I did some
initial investigations with WinPOPT to obtain good sampling time points, and
then later on simulated two different study designs:
· Parallel design, 8 subjects with single dose of dose strength A and 8
subjects with single dose of dose strength B. Sampling time until 32 h after
dosing.
· Crossover design with 24 h interval between doses; 8 subjects with
single dose of dose strength A and then single dose of B after 24 h, and the
other 8 subjects with single dose of dose strength B and then single dose of A
after 24 h. Sampling time points for each dose exactly like in the parallel
design, with the exception that the first dose can only be sampled until 24 h
after the dose, because then the next dose is administered.
My problem: The parallel design looks great for estimation of CL and F1,
whereas for V2 and KA it is imprecise (while still accurate). Now I thought
that I might switch to the crossover design, because this contains a lot more
information (basically each subject with two doses instead of only one, subject
number the same). In theory, I expected a better estimation of KA, i.e. higher
precision, because the design would enable the estimation of the IOV component
as well. But what it seems like is that CL is estimated less precisely and for
F1, a bias is introduced (simulated F1 of 1, estimated around 0.9). How can the
parameter estimates become worse in the simulations when I only add information
that should fit the model?
Thanks and best regards
Nele
______________________________________________________________
Dr. Nele Käßner
PK/PD Sciences
Modelling and Simulation (RDP/MS)
Nycomed GmbH
Byk-Gulden-Str. 2
D-78467 Konstanz, Germany
Fon: (+49) 7531 / 84 - 4759
Fax: (+49) 7531 / 84 - 94759
mailto: [email protected]<mailto:[email protected]>
http://www.nycomed.com/
County Court: Freiburg, Commercial Register HRB 701257
Chairman Supervisory Board: Charles Depasse
Management Board: Stefan Brinkmann, Dr. Frederik Bendiksen,
Gilbert Rademacher, Dr. Rainer Wiartalla
--------------------------------------------------------------------
The content of this email and of any files transmitted may contain
confidential, proprietary or legally privileged information and is intended
solely for the use of the person/s or entity/ies to whom it is addressed. If
you have received this email in error you have no permission whatsoever to use,
copy, disclose or forward all or any of its contents. Please immediately notify
the sender and thereafter delete this email and any attachments.