Re: AW: Time 'T' in $Error
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
Quoted reply history
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:[email protected]]
> *Gesendet:* 27 July 2015 17:34
>
> *An:* Katrin Volz < [email protected] >; [email protected]
>
> *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:* [email protected] < mailto: [email protected] > [ mailto: [email protected] ] *On Behalf Of *Katrin Volz
>
> *Sent:* Monday, July 27, 2015 10:46 AM
> *To:* [email protected] <mailto:[email protected]>
> *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
>
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