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.den...@pfizer.com]
*Gesendet:* 27 July 2015 17:34
*An:* Katrin Volz <ankekatrin.v...@uni-saarland.de>;
nmusers@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-nmus...@globomaxnm.com
<mailto:owner-nmus...@globomaxnm.com>
[mailto:owner-nmus...@globomaxnm.com] *On Behalf Of *Katrin Volz
*Sent:* Monday, July 27, 2015 10:46 AM
*To:* nmusers@globomaxnm.com <mailto:nmusers@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.v...@uni-saarland.de
<mailto:ankekatrin.v...@uni-saarland.de>
fon +49 [0]681 302 22 84
fax +49 [0]681 302 70 258
www.clinicalpharmacy.me <http://www.clinicalpharmacy.me>
