From: Nick Holford <*n.holford*>

Date: Fri, 28 May 2010 20:50:51 +0100

For estimation NONMEM estimates one parameter to describe the

distribution of random effects -- this is the variance (OMEGA) of the

distribution. Thus it makes no explicit assumption that the distribution

is normal. AFAIK any distribution has a variance.

For simulation NONMEM assumes all etas are normally distributed. If you

use OMEGA BLOCK(*) then the distribution is multivariate with

covariances but still normal.

Nick

Ethan Wu wrote:

*> I could not find in the NONMEM help guide that explicitly mentioned a
*

*> normal distribution is assumed, only it was clearly mentioned of
*

*> assumption of mean of zero.
*

*>
*

*> ------------------------------------------------------------------------
*

*> *From:* Serge Guzy <GUZY *

*> *To:* Ethan Wu <ethan.wu75 *

*> *Sent:* Fri, May 28, 2010 1:25:24 PM
*

*> *Subject:* RE: [NMusers] distribution assumption of Eta in NONMEM
*

*>
*

*> As far as I know, this is the assumption in most of the population
*

*> programs like NONMEM, SADAPT, PDX-MC-PEM and SAEM. Therefore when you
*

*> simulate, random values from a normal distribution are generated.
*

*> However, you have the flexibility to use any transformation to create
*

*> distributions for your model parameters that will depart from pure
*

*> normality. For example, CL=theta(1)*exp(eta(1)) will generate a
*

*> log-normal distribution for the clearance although the random deviates
*

*> are all from the normal distribution.
*

*>
*

*> I am not sure how you can simulate data sets if you are using the non
*

*> parametric option that is indeed available in NONMEM.
*

*>
*

*> Serge Guzy; Ph.D
*

*>
*

*> President, CEO, POP_PHARM
*

*>
*

*> www.poppharm.com <http://www.poppharm.com/>
*

*>
*

*>
*

*>
*

*>
*

*>
*

*>
*

*>
*

*>
*

*>
*

*> *From:* owner-nmusers *

*> [mailto:owner-nmusers *

*> *Sent:* Friday, May 28, 2010 9:08 AM
*

*> *To:* nmusers *

*> *Subject:* [NMusers] distribution assumption of Eta in NONMEM
*

*>
*

*>
*

*>
*

*> Dear users,
*

*>
*

*> Is it true NONMEM dose not assume Eta a normal distribution?
*

*>
*

*> If it does not, I wonder what distribution it assumes? I guess this
*

*> is critical when we do simulations.
*

*>
*

*> Thanks
*

*>
*

*>
*

*>
*

*>
*

*>
*

*>
*

*> ------------------------------------------------------------------------
*

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*>
*

--

Nick Holford, Professor Clinical Pharmacology

Dept Pharmacology & Clinical Pharmacology

University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand

tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53

email: n.holford

http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

Received on Fri May 28 2010 - 15:50:51 EDT

Date: Fri, 28 May 2010 20:50:51 +0100

For estimation NONMEM estimates one parameter to describe the

distribution of random effects -- this is the variance (OMEGA) of the

distribution. Thus it makes no explicit assumption that the distribution

is normal. AFAIK any distribution has a variance.

For simulation NONMEM assumes all etas are normally distributed. If you

use OMEGA BLOCK(*) then the distribution is multivariate with

covariances but still normal.

Nick

Ethan Wu wrote:

--

Nick Holford, Professor Clinical Pharmacology

Dept Pharmacology & Clinical Pharmacology

University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand

tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53

email: n.holford

http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

Received on Fri May 28 2010 - 15:50:51 EDT