RE: [NMusers] Model Comparison and Viewing of Output

Dear Nitin,

 

If I interpret your first question narrowly, we did a study that at least
partly addressed this (Wahlby U, Bouw MR, Jonsson EN, Karlsson MO.
Assessment of type I error rates for the statistical sub-model in NONMEM. J
Pharmacokinet Pharmacodyn 2002;29(3):251-69.) The conclusion was that there
seems to be some basis for using the OFV in likelihood ratio tests for
looking at aspects of the variability models. However, such tests are
sensitive to aspects like method used, shape of the distribution, etc. The
final paragraph was:

"In conclusion, the LR test is not reliable for the statistical sub-model

if the FO method is used. For the FOCE INTER method, the LR test is

appropriate when the underlying assumptions of normality of residuals hold

true and data per individual are not too sparse. Deviations from normality,

which can be diagnosed from the modeling output, may cause estimated

type I error rates that deviate markedly from the expected. The type I error

rates for inclusion of variance and covariance parameters are the most
affected

by deviations from normality, while those for covariates on variance

parameters are more robust."

 

Best regards,

Mats

 


Mats Karlsson, PhD
Professor of Pharmacometrics
Div. of Pharmacokinetics and Drug Therapy
Dept. of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
SE-751 24 Uppsala
Sweden
phone +46 18 471 4105
fax +46 18 471 4003
mats.karlsson_at_farmbio.uu.se

  _____


From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On
Behalf Of Nitin Mehrotra
Sent: Tuesday, August 14, 2007 18:19
To: nmusers_at_globomaxnm.com
Subject: [NMusers] Model Comparison and Viewing of Output

 

Dear NMusers,

 

I had a couple of questions for the group members:

 

1. Model Comparison: Everything else remaining the same in a model, should a
drop in the objective function on addition of an eta, sigma or a covariance
term reflect an improvement in a model. Or comparing AICs, considering eta's
and sigma's as additional parameters a correct approach. I understand that
these decisions are rather based on multiple criterias like goodness of fit
plots, biological sense, physiological plausibility of the parameter
estimates etc. But specifically would like to know whether comparing
objective function among these models a logical approach?

 

2. Viewing Output via $TABLE option: When we do simulation using NONMEM,the
output file contains both the dosing and observation records. Is there a way
in NONMEM to specify a priori in the control stream, such that only
observation records could be obtained in the simulation output file?

 

Thanks and Regards

 

Nitin Mehrotra

 

Nitin Mehrotra, Ph.D

Post Doctoral Research Fellow

874 Union Avenue, Suite4.5p/5p

Department of Pharmaceutical Sciences

University of Tennessee Health Science Center

Memphis, TN, USA-38163

901-448-3385 (Lab)

nmehrotr_at_utmem.edu

 

  

  _____

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Received on Wed Aug 15 2007 - 01:19:54 EDT