NONMEM Users Network Archive

Hosted by Cognigen

RE: NONMEM code verification

From: Bauer, Robert <Robert.Bauer>
Date: Thu, 21 Jan 2016 20:02:59 +0000

The most common reason NONMEM may produce a different result than expected =
is if the evaluation depends on covariates listed in the data set that chan=
ges with each record, the default action of NONMEM is for an interval cover=
ing T1>Time<=T2, it uses the covariate at record TIME=T2. This behavio=
r 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=

Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics R&D
ICON Early Phase
Office: (215) 616-6428
Mobile: (925) 286-0769

From: owner-nmusers
 Behalf Of Nick Holford
Sent: Thursday, January 21, 2016 11:33 AM
To: nmusers
Subject: Re: [NMusers] NONMEM code verification


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,


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<>

"Declarative languages are a form of dementia -- they have no memory of eve=

Holford SD, Allegaert K, Anderson BJ, Kukanich B, Sousa AB, Steinman A, Pyp=
endop, B., Mehvar, R., Giorgi, M., Holford,N.H.G. Parent-metabolite pharmac=
okinetic models - tests of assumptions and predictions. Journal of Pharmaco=
logy & Clinical Toxicology. 2014;2(2):1023-34.
Holford N. Clinical pharmacology = disease progression + drug action. Br =
J Clin Pharmacol. 2015;79(1):18-27. <br /><br /> ICON plc made the foll=
owing annotations. ------------------------------------------------------=
------------------------ This e-mail transmission may contain confidentia=
l or legally privileged information that is intended only for the individua=
l or entity named in the e-mail address. If you are not the intended reci=
pient, you are hereby notified that any disclosure, copying, distribution, =
or reliance upon the contents of this e-mail is strictly prohibited. If y=
ou have received this e-mail transmission in error, please reply to the sen=
der, so that ICON plc can arrange for proper delivery, and then please dele=
te the message. Thank You, ICON plc South County Business Park=

Received on Thu Jan 21 2016 - 15:02:59 EST

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to:

Once subscribed, you may contribute to the discussion by emailing: