AW: Time 'T' in $Error

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

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

Dear Katrin, You still could code your model in $ERROR using TIME, as your diurnal rhythm is proportional to baseline. If you would like to explore indirect models, you could try the harmonic approach as described in Chakraborty et al. 1999 - http://europepmc.org/abstract/med/10533696 ; the beauty is that you can model the baseline in $PRED and use these estimates right into $DES for your drug effect on kin. For blood pressure rhythms you might also want to try the more flexible model laid out by Sallstrom et al. 2005, http://europepmc.org/abstract/med/16328099. Hope this helps, Jeroen -- http://pd-value.com [email protected] @PD_value +31 6 23118438 -- More value out of your data! Op 28-07-15 om 08:07 schreef Katrin Volz: > 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 > > Clinical Pharmacy > > Campus C2 2 | Room 0.31 > > D- 66123 Saarbrücken > > mail [email protected] < mailto: [email protected] > > > fon +49 [0]681 302 22 84 > > fax +49 [0]681 302 70 258 > > www.clinicalpharmacy.me http://www.clinicalpharmacy.me