RE: Modeling Cmin and Tmin
Dear Friederike,
Please, step back for one minute and try to understand what you want to find
out: You are applying a nonlinear mixed-effects modelling program to obtain
parameter values for your model. All parameters in your model are random
variables. Some have a mean of zero (ETAs, EPSs) some should have a mean <>
0 (THETAs). Your results are not point estimates but distributions.
Therefore you should approach the question of Cmin and Tmin through
simulation and report the confidence interval (or other stats) for your
parameters of interest. Thus construct a simulation data set with dense
time points around the expected Tmin, and run
$SIMULATION (240311) ONLYSIMULATION SUBPROBLEMS=1000
$TABLE ID TIME ...... NOHEADER NOAPPEND NOPRINT FILE=xxxx.tab
with all your final parameter estimates as initial values in your control
file. Then analyse your 100 (or 1000) simulated data files with R or SAS and
report the distribution of the Cmin and Tmin you found.
Please, come back with more questions in case I have confused you,
Joachim
Joachim Grevel, PhD
Scientific Director
BAST Inc Limited
BioCity Nottingham
Pennyfoot Street
Nottingham, NG1 1GF
Tel: +44 (0)115 8120497
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Friederike Kanefendt
Sent: 06 April 2011 09:56
To: [email protected]
Subject: [NMusers] Modeling Cmin and Tmin
Dear NMUser,
I am a beginner in NONMEM and I have a question regarding modeling Cmin and
Tmin.
I have data of a biomarker which decreases after drug intake and I want to
determine the minimum change from baseline (Cmin) as well as the
corresponding time (Tmin). I tried different models but the estimated values
for these parameters are not plausible or always zero.
Has someone experience with this or any idea to solve this problem?
Thanks a lot
Best regards
Friederike
Attached I send you a part of my code:
$SUBROUTINE ADVAN6 TOL=3
...
$DES
...
DADT(5) = KIN*INH-KOUT*A(5) ; Biomarker CMT
IF(TIME.EQ.0) THEN
CMIN = BASE ; Baseline conc also
estimated by NM
TMIN=0
ENDIF
CC=A(5)
IF(CC.LT.CMIN) THEN
CMIN= CC
TMIN= T
ENDIF
REL = CMIN/BASE ; change relative to baseline
...
$ESTIMATION SIG=2 PRINT=1 METHOD=1 INTER MAXEVAL=0 NOABORT
Friederike Kanefendt
Pharmacist, PhD-Student
University of Bonn
-Clinical Pharmacy-
An der Immenburg 4
D-53121 Bonn
Phone: +49 (0)228 73-5781
Fax: +49(0) 228 73-9757
[email protected]