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Re: Build a cell-cycle based tumor growth model

From: Nick Holford <n.holford>
Date: Thu, 17 Jul 2008 22:02:08 +1200

Feng,

There is no need to worry about compartment numbers to match your
observations. The CMT data item is only needed when you have to identify
a compartment for an AMT. With NONMEM VI it is no longer necessary to
use CMT and AMT to initialize compartments. If you are still using
NONMEM V it is time you updated your system.

I use my own named data item called DVID to identify different types of
observations e.g.

$INPUT ID TIME DVID DV L2

where DVID could range from 1 to 4 to define the 4 different
observations. You could use it in $ERROR like this.

IF (DVID.EQ.1) THEN
   Y=A(1)+EPS(1)
ENDIF
...
IF (DVID.EQ.4) THEN
   Y=A(4)+EPS(4)
ENDIF

I am not really sure how to reply to your other questions because I dont
know which things you are measuring. Do you have observations of G1, S,
G2 and M? Do you also have a measurement of tumour size? Please give us
an idea of what differential equations you think you need to describe
the biomarkers you mention.

Nick

Feng Yang wrote:
> Dear nmusers:
> Recently I am trying to build a cell-cycle based tumor growth model,
> i.e. tumor size = G1+ S + G2 + M. Meanwhile, I have quite a few
> simultaneous biomarkers to characterize the cycle behaviors. Those
> biomarkers could be calculated based on the population of G1, S, G2,
> and M. I have the following puzzles needed to be addressed:
>
> 1) In my data file, what is the CMT number I should give to those
> observations (such as tumor size and many biomarkers)? By the way, I
> need CMT to specify/initialize the corresponding compartment. Since
> I am not quite sure how to use L2 and PCMT, I tried many times, all
> failed except the following foolish way:
> I create one more compartment to hold the tumor size:
> DADT(iTUMROR) = DADT(iG1) + DADT(iS) + DADT(iG2) + DADT(iM)
> and in my data file, I put the CMT compartment created (iTUMOR) into
> the observation of tumor size.
>
> However, for all other biomarkers, there is no way to write this kind
> of DADT equations. How could I solve this in a smart way?
>
> 2) Since some biomarker data are collected based on certain time
> point, saying t0. In other words, they are relative fold-changes
> compared to the vehicle at t0. Therefore, I need to save the
> intermediate population of G1, S, G2 and M at t0, as constants, which
> will be used to scale the later-on populations so that the model
> predictions are comparable with the observations.
>
> However, in the both block $DES and $ERROR, there is no way to save
> these intermediate populations as global variables or constants. I
> guess, I have to use MSFO to separate the simulation to many
> sections? But it am not sure how to do it.
>
> Your thoughts and feedback are really appreciated! Thanks a lot!
>
> Feng
>
>

--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
n.holford
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

Received on Thu Jul 17 2008 - 06:02:08 EDT

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