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Re: Fwd: T in $DES

From: Alex Zheng <cnzhenghan>
Date: Thu, 8 Jul 2021 17:55:18 -0700

Hi Jakob,

My guess is that the differential equations are solved in the numeric ODE
solver, so that the variable T is updated in each iteration of the
estimation step.

For time zero, the variable T is not updated because the value is supposed
to be the initial value, which probably results in getting the value
computed in the last iteration.

This is just my theory.

Best wishes,

Han Zheng MD, PhD

Shanghai BioGuider Medical Technology Co., Ltd.

On 6 July 2021 at 10:54:45 pm, Matts Kågedal (mattskagedal

Thanks Jakob and Dennis for helpful comments!
I think the model is doing what it should. My problem is that I don't get
an accurate output of the covariate prediction at time zero when computed
inside $DES based on T_DAY (where T_DAY=T).
As a workaround I now also derive the predicted covariate value in $PK
based on TIME (from the dataset) just for output in $TABLE. This seems to
be working.


On Tue, Jul 6, 2021 at 3:15 PM Jakob Ribbing <jakob.ribbing

> Dear Matts,
> Did you get funny results in the way that using T_DAY did now work as
> intended?
> If you are unsure you could set up a simple test where you have the
> analytical solution to the output, as an initial confirmation.
> Otherwise, for models integrating forward in time, a covariate value at
> time zero (or subjects first time point) would not have an impact on the
> model fit or parameter value, as nonmem would look forward towards the ne=
> record in time.
> $DES isspecial since the solver may move back and forth and time is
> updated in-between data records, but what you try to do may still work fi=
> The output in the table at time zero would be the subject’s last =
> because it has not yet entered $DES at time zero, but integrating forward
> that should not impact the fit (I believe).
> Best regards
> Jakob
> On 6 Jul 2021, at 14:44, Matts Kågedal <mattskagedal
> Hi all,
> I have a question regaring T in $DES.
> I have a time-varying covariate that is derived based on an explicit
> equation and then use in a differential equation.
> I got some funny results in the output table and investigated a bit
> further.
> I therefore derived T_DAY=T in $DES as below and output it in $TABLE.
> Why is T_DAY at TIME=0 equal to the time of the last observation for th=
> patient? I was expecting it to be Zero (same as Time). Seems to be the sa=
> for all IDs in the dataset.
> Below is the output created in $TABLE including the "derived" variable
> T_DAY.
> Any advice would be appreciated.
> Matts Kågedal
> <image.png>
> <image.png>
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Received on Thu Jul 08 2021 - 20:55:18 EDT

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