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Re: AW: [NMusers] Time 'T' in $Error

From: sbihorel <Sebastien.Bihorel_at_cognigencorp.com>
Date: Tue, 28 Jul 2015 09:09:50 -0400

Hi,

 From a purely technical point of view, you can use TIME in your $ERROR
record if you want to implement your drug effect as a direct effect on
top of the circadian rhythm (this type of model may or may not
appropriate, I leave you judge of that).

SinfS = ( 1 + Amplitude * sin ( (2*PI/Period) * (TIME-Phase) ) )
SBP = (SBas + SinfS) * (1-EffS)

In a direct effect model, you only need to evaluate your PD endpoint at
the value of TIME that were observed/included in your dataset, because
you only need the value of your drug concentration at a given time to
calculate the value of the effect at this time.

If you want to implement a circadian rhythm in an indirect response
model, you will have to derive your sine/consine function of time and
use it in $DES. There are multiple papers from Dr. Jusko's team on the
topic, eg:

http://www.ncbi.nlm.nih.gov/pubmed/10672436

Sebastien

On 7/28/2015 2:07 AM, Katrin Volz wrote:
>
> Dear Bill, dear all
>
> Thanks so much for your answer.
>
> More concrete I would like to model blood pressure including a
> circadian rhythm. Therefore I would like to use a sine or cosine
> function with ‘T’ instead of ‘Time’.
>
> SinfS = ( 1 + Amplitude * sin ( (2*PI/Period) * (T-Phase) ) ) ; sine
> or cosine function
>
> SBP = (SBas + SinfS) * (1-EffS)
> ; SBP = systolic
> blood pressure, SBas = Baseline systolic blood pressure, (1-EffS = effect)
>
> I could also model this effect using a turnover model and avoid this
> problem, but I would like to evaluate this kind of PD model (if there
> is any meaningful way to code).
>
> I also had the idea to code this sine function as a function of time
> in a compartment and rename this compartment in $Error, but I am not
> sure if there is any way to do this.
>
> Thanks again and best regards.
>
> Katrin
>
> *Von:*Denney, William S. [mailto:William.S.Denney_at_pfizer.com]
> *Gesendet:* 27 July 2015 17:34
> *An:* Katrin Volz <ankekatrin.volz_at_uni-saarland.de>;
> nmusers_at_globomaxnm.com
> *Betreff:* RE: [NMusers] Time 'T' in $Error
>
> Hi Katrin,
>
> $ERROR is executed once per data row. The time when $ERROR is run is
> the TIME value (the discrete times of the measurement). For this
> specific example, you can just use TIME. You will need to code your
> $DES block so that what you’re wanting to integrate as a function of
> time is in a compartment amount (e.g. A(1)). With your example, it’s
> hard to see how T is used in the $DES, but perhaps you could share the
> real example to give a bit more concrete advice on how to integrate
> the answer into your code.
>
> Thanks,
>
> Bill
>
> *From:*owner-nmusers_at_globomaxnm.com
> <mailto:owner-nmusers_at_globomaxnm.com>
> [mailto:owner-nmusers_at_globomaxnm.com] *On Behalf Of *Katrin Volz
> *Sent:* Monday, July 27, 2015 10:46 AM
> *To:* nmusers_at_globomaxnm.com <mailto:nmusers_at_globomaxnm.com>
> *Subject:* [NMusers] Time 'T' in $Error
>
> Dear NMuser,
>
> I would like to model a PD effect using a function which includes
> continuous time ‘ T ’.
>
> The PD Effect is coded in $Error.
>
> In general like this:
>
> *$ERROR*
>
> MyFunction = xxx + T
>
> PDEffect = Basline * MyFunction
>
> But ‘T’ cannot be used in $Error.
>
> I tried to code the function with ‘T’ in $DES and rename it to use it
> in $ERROR:
>
> *$DES*
>
> MyFunction = xxx + T
>
> *$ERROR*
>
> MyNewFunction = MyFunction
>
> PDEffect = Baseline * MyNewFunction
>
> but it didn’t worked (to rename was not permitted by NONMEM).
>
> Does anyone of you has an idea how to solve this problem?
>
> Thanks and best regards.
>
> Katrin
>
> Anke-Katrin Volz
>
> PhD Student
>
> Saarland University
>
> Clinical Pharmacy
>
> Campus C2 2 | Room 0.31
>
> D- 66123 Saarbrücken
>
> mail ankekatrin.volz_at_uni-saarland.de
> <mailto:ankekatrin.volz_at_uni-saarland.de>
>
> fon +49 [0]681 302 22 84
>
> fax +49 [0]681 302 70 258
>
> www.clinicalpharmacy.me <http://www.clinicalpharmacy.me>
>


Received on Tue Jul 28 2015 - 09:09:50 EDT

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