NONMEM Users Network Archive

Hosted by Cognigen

RE: Mixture modelling (responders vs non-responders)

From: Farrell, Colm <Colm.Farrell>
Date: Tue, 20 Jul 2010 09:41:57 +0100

Hi Zhong,
 
If you have clear non-responders, you might consider allowing
non-responders and responders to have different response functions
rather than different parameter estimates.
 
For the non-responders, response=constant (i.e., baseline) and for
responders, response=function(AUC(0-tau)).
 
Regards,
Colm
 
________________________________

From: owner-nmusers
On Behalf Of Zhong Chen
Sent: Monday, July 19, 2010 6:00 PM
To: nmusers
Subject: [NMusers] Mixture modelling (responders vs non-responders)



Hi NMUsers,

I am trying to model some data that contain a biomarker time course over
4 weeks (with twice weekly measurements) and steady state of the change
in biomarker is attained in this duration in the presence of various
doses of a drug. This is a dose ranging experiment and I have value of
exposure (AUC(0-tau)) at steady state that drives the biomarker change.
I noticed that there are some obvious non-responders to the treatment
(no mechanistic/physiological explanation). When using a direct effect
Emax model the model fits are good and parameter estimates are well
estimated. But the estimate of omega for EAUC50 is extremely high (about
13) due to the very high values estimated for the non-responders, thus
simulations are extremely biased. I tried a mixture model on EAUC50 and
NONMEM estimated 15% non-responders with high EAUC50 values (while
examining the dataset non-responders are about 25%). With the mixture
model implementation on EACU50 the omega on EAUC50 dropped to about 4
which is again extremely high for the responder population. I tried
mixture model on Emax alone and EAUC50+Emax together also but again got
high omegas and lower than expected estimate of non-responder
population.

I would appreciate if I can get some ideas to take care of this issue.
THANKS!!

Z Chen



ICON plc made the following annotations.
-------------------------------------------------------------------------=
-----
This e-mail transmission may contain confidential or legally privileged i=
nformation
that is intended only for the individual or entity named in the e-mail ad=
dress. If you
are not the intended recipient, you are hereby notified that any disclosu=
re, copying,
distribution, or reliance upon the contents of this e-mail is strictly pr=
ohibited. If
you have received this e-mail transmission in error, please reply to the =
sender, so that
ICON plc can arrange for proper delivery, and then please delete the mess=
age.
Thank You,
ICON plc
South County Business Park
Leopardstown
Dublin 18
Ireland
Registered number: 145835

Received on Tue Jul 20 2010 - 04:41:57 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.