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individual dosing scheme #260

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RKasp opened this Issue Dec 10, 2018 · 7 comments

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@RKasp
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RKasp commented Dec 10, 2018

Dear all,
I am working on a population data set in which almost every subject ID has an individual dose varying with PD response, thus cannot be normalized by BW. Is there a possibility to work around cloning the simulation for each dose and individual? It seems to greatly lengthen run times for model optimization. Alternatively, I am considering to simulate a low, medium and high dose, however, I would only be able to use a fraction of data for parameter identification.
Your help is greatly appreciated. Thank you.

Best regards,

Rudiger

@StephanSchaller

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StephanSchaller commented Dec 10, 2018

Dear Rudiger,

I guess it depends. If you do not think there is a BW dependence in you PK, you could post-hoc normalize all the doses by BW and then group them by the resulting normalized doses.
If the resulting doses are spread out continuously, you will not get around creating a simulation for each dose (if I understood your setup correctly).

Hope this helps,
Stephan

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StephanSchaller commented Dec 10, 2018

additional remark: if you group by low / medium / high and the doses in each group are not identical (BW normalized) you will in principal use wrong data for fitting most of your doses.

@RKasp

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RKasp commented Dec 11, 2018

Hi Stephan,

thank you for your input. I will explore further but you understood correctly, the doses are spread out continuously. It seems I may need to take the more cumbersome route. The simulation of a low, medium and high dose was meant to be more descriptive. I have not explored PKSim in R much yet, but would it be possible theoretically to come up with a script to account for this situation?

Best regards,

Rudiger

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StephanSchaller commented Dec 11, 2018

Hi Rudiger,

i would say the PK-Sim/R combo is the ideal alternative setup to do a post-hoc analysis of a clinical trial, if you are willing to do some scripting/coding in R.

You would only need to set up your model for one representative individual in PK-Sim, all the rest (loading data, settting the dose and exchanging subject physiology) can be done in R in a convenient (scripted) way.

Best,
Stephan

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RKasp commented Dec 13, 2018

Hi Stephan,
I will spend the time on R and get back to you soon.
Thank you for your help.
Regards,
Rudiger

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msevestre commented Dec 13, 2018

Hi @RKasp,

How many individuals are we talking about here? If you go to R, you won't have access to the parameter identification for example so while you'll be able to script out updating the dose etc, it might not fulfill your need.

While you cannot vary the dose EXPLICITLY in a PK-Sim population, there are ways to do it (for example by exporting to MoBi and back to PK-Sim). We also have a feature request here to add dose as a user defined parameter. If we get enough interest there, it might make it to the next release.

Cheers, Michael

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StephanSchaller commented Dec 13, 2018

If you go to R, you won't have access to the parameter identification

R has a number of packages for parameter identification (i.e. solving inverse problems for linear and nonlinear dynamical systems). One of these is the "FME" package.

But of course, if the number of individuals is not too many, staying withing PKSim is certainly the easier way, depending on your skills in R.

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