NONMEM Users Network Archive

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Re: NONMEM code verification

From: Kyle Baron <kyleb>
Date: Thu, 21 Jan 2016 15:41:58 -0600

If working in R, you can use mrgsolve:
http://metrumrg.com/opensourcetools.html

It is open-source, validated R package interfacing with DLSODA solver in
ODEPACK.

It should be able to directly utilize your NONMEM data set:
http://metrumrg.com/mrgsolve-howdoi.html#implement-events-via-data-set
(you might need to rename some columns ... use tolower() or mrgsolve has a
function to do it).

If you're really making a really close comparison, pay attention to the
solver tolerances and the number of digits in the answer (you can control
them in both NONMEM and mrgsolve). Caution: mrgsolve advances with the
covariate at T1 (in Bob's example). But I guess I'd tend to take that
factor out of play and just look at predictions from some parameters
constant over time where possible (assuming you're really wanting to
diagnose what is happening with the ODEs; that's how I understood Nick's
post).

Kyle


On Thu, Jan 21, 2016 at 2:02 PM, Bauer, Robert <Robert.Bauer
wrote:

> Ana:
>
> The most common reason NONMEM may produce a different result than expecte=
d
> is if the evaluation depends on covariates listed in the data set that
> changes with each record, the default action of NONMEM is for an interval
> covering T1>Time<=T2, it uses the covariate at record TIME=T2. This
> behavior can be changed with $BIND. Also, if you program in
> discontinuities that vary with model parameters, like changing a rate
> constant suddenly, you may want to use the MTIME() system. Both of these
> items are discussed in viii.pdf.
>
>
>
>
>
>
>
> Robert J. Bauer, Ph.D.
>
> Vice President, Pharmacometrics R&D
>
> ICON Early Phase
>
> Office: (215) 616-6428
>
> Mobile: (925) 286-0769
>
> Robert.Bauer
>
> www.iconplc.com
>
>
>
> *From:* owner-nmusers
]
> *On Behalf Of *Nick Holford
> *Sent:* Thursday, January 21, 2016 11:33 AM
> *To:* nmusers
> *Subject:* Re: [NMusers] NONMEM code verification
>
>
>
> Ana,
>
>
> I call this process fixed effect (or deterministic) model qualification.
>
> I code complex models using Berkeley Madonna then run NONMEM without any
> $EST or $SIM records. The NONMEM PRED values should agree with the
> Berkeley Madonna predictions if your structural model is coded the same
> way in both systems.
>
> Best wishes,
>
> Nick
>
> On 20-Jan-16 11:14, Ana Miranda Bastos wrote:
> >
> > Hi,
> >
> >
> > I have a complex model with manually coded ODEs and multiple
> > compartments. VPC etc seem ok but simulation results are getting a bit
> > weird.
> >
> >
> > I'd like to find out what people use to ensure that the NONMEM code
> > written really represents the set of ODEs written on paper. Just to
> > clarify, this is just to make sure the NONMEM instructions are
> > actually a correct representation of the mathematical description of
> > the model, not if the model is a correct representation of the biology
> > at this stage.
> >
> >
> > This problem is not so obvious when you use the built-in macros but
> > once the model grows complex, and has a lot manual inputs, it is more
> > likely that a bug creeps in.
> >
> >
> > I'm looking for something more stringent than a code review by a peer.
> >
> >
> > Thank you advance for your time and attention,
> >
> >
> > Ana
> >
> >
> > ------------------------------------------
> > Ana Bastos, Pharm, MSc, PhD student
> > Pharmacologie cellulaire et moléculaire
> > (Cellular and Molecular Pharmacology Unit)
> > Louvain Drug Research Institute
> > Université catholique de Louvain (Catholic University of Louvain)
> > UCL 7370 avenue E. Mounier 73
> > 1200 Bruxelles, Belgique
> >
>
> --
> Nick Holford, Professor Clinical Pharmacology
> Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A
> University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
> office:+64(9)923-6730 mobile:NZ+64(21)46 23 53
> email: n.holford
> http://holford.fmhs.auckland.ac.nz/
>
> "Declarative languages are a form of dementia -- they have no memory of
> events"
>
> Holford SD, Allegaert K, Anderson BJ, Kukanich B, Sousa AB, Steinman A,
> Pypendop, B., Mehvar, R., Giorgi, M., Holford,N.H.G. Parent-metabolite
> pharmacokinetic models - tests of assumptions and predictions. Journal of
> Pharmacology & Clinical Toxicology. 2014;2(2):1023-34.
> Holford N. Clinical pharmacology = disease progression + drug action. B=
r J
> Clin Pharmacol. 2015;79(1):18-27.
>
>
>
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--
Kyle Baron
Metrum Research Group
860-735-7043, Ext. 202
kyleb

Received on Thu Jan 21 2016 - 16:41:58 EST

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