From: Joachim Grevel <*jgrevel*>

Date: Fri, 24 Feb 2012 12:37:06 -0000

Dear all,

The NONMEM control file of Example 1 in the USERs GUIDE to NONMEM 7.2 =

pp.

108/128 tells us how to work with priors:

; Prior information to the OMEGAS (NETPxNETP of them).

$OMEGA BLOCK(4)

0.2 FIX

0.0 0.2

0.0 0.0 0.2

0.0 0.0 0.0 0.2

; Degrees of freedom to prior OMEGA matrix (1 for each Omega Prior =

block).

; Because degrees of freedom is very low, equal to the

; the dimension of the prior OMEGA, this means that the prior =

information to

the OMEGAS is

; highly uninformative

$THETA (4 FIX)

This is what I use with NONMEM 7.2

; when I follow the instruction and use inverse Wishart to represent the

OMEGA of my previous NONMEM analysis (2500 conc in 200 patients).

$OMEGA BLOCK(2)

0.000135 FIX

0.0000195 0.000640

; I want to make the priors informative and calculated df according to =

the

proposal by Mats.

$THETA (138 FIX)

; when I do not follow the instruction and use simply the covariance =

matrix

of the previous NONMEM analysis of the large data file:

$OMEGA BLOCK(2)

0.000131 FIX

0.0000191 0.000627

$THETA (138 FIX)

There is not really a big difference in my example.

Joachim

Joachim Grevel, PhD

Scientific Director

BAST Inc Limited

BioCity Nottingham

Pennyfoot Street

Nottingham, NG1 1GF

Tel: +44 (0)115 8120497

From: owner-nmusers

On

Behalf Of Stephen Duffull

Sent: 22 February 2012 17:46

To: Mats Karlsson; 'Joachim Grevel'; 'Coen van Hasselt'; 'nmusers'

Subject: RE: [NMusers] OMEGA priors using modes of inverse Wishart =

matrix

Hi

An appropriate value for dof of the IW is difficult to determine. While =

it

can be set at n-1 from a prior this is somewhat arbitrary. It is not in

this sense like a t-distn where we calculate dof in this manner.

You would have to get a feeling for the degree of spread in your =

deviates

given your guess at OMEGA(0) and dof. This can be done by simulation or =

in

special circumstances by direct calculation.

Steve

--

From: owner-nmusers

On

Behalf Of Mats Karlsson

Sent: Thursday, 23 February 2012 3:58 a.m.

To: 'Joachim Grevel'; 'Coen van Hasselt'; 'nmusers'

Subject: RE: [NMusers] OMEGA priors using modes of inverse Wishart =

matrix

Dear Joachim,

The IW distribution is not something you get from NONMEM, you have to =

give

the degrees of freedom of the IW prior distribution. Normally this is at =

or

below the number of subjects in you previous study depending the =

information

about the parameter per subject.

In addition to User’s Guides, you may find useful info in Gisleskog et =

al J

Pharmacokinet Pharmacodyn. 2002 Dec;29(5-6):473-505.

Best regards,

Mats

Mats Karlsson, PhD

Professor of Pharmacometrics

Dept of Pharmaceutical Biosciences

Faculty of Pharmacy

Uppsala University

Box 591

75124 Uppsala

Phone: +46 18 4714105

Fax + 46 18 4714003

From: owner-nmusers

On

Behalf Of Joachim Grevel

Sent: 22 February 2012 15:24

To: 'Coen van Hasselt'; nmusers

Subject: RE: [NMusers] OMEGA priors using modes of inverse Wishart =

matrix

Dear Coen,

There I do have the answer: with MCMC Bayesian in NONMEM 7.1 you have to =

use

NWPRI according to the guide.

Dear Nidal,

What I try to do is that: use an existing very well defined popPK model

(2500 conc in 200 patients) to obtain individual PK parameters in only =

20

additional patients that have sparse sampling (2 to 4 conc per patient). =

I

was planning to use informative priors rather than add 80 conc to a =

bulk of

2500 conc. What do you think?

Thanks to all, specifically Tim!

Joachim

From: Coen van Hasselt [mailto:Coen.vanHasselt

Sent: 22 February 2012 14:03

To: jgrevel

Subject: Re: [NMusers] OMEGA priors using modes of inverse Wishart =

matrix

Dear Joachim,

I have always wondered about this particular question myself as well..

Thanks for asking at NMusers.

Another thing related to the PRIORs I was wondering about: you can =

either

use NWPRI (i.e. with the inverse wishart for OMEGA's), or TNPRI, which =

uses

a multivariate normal for the OMEGA's. Do you have any idea when to use

either of these two possible implementations ?

Thanks,

Coen

*>>> "Joachim Grevel" 02/22/12 2:11 PM >>>
*

Dear NMusers,

Our NONMEM User Guides are full of good advice and they are searchable. =

Yet

when I tried to find out whether any of the estimation methods could be

enticed to give me the ?inverse Wishart matrix? needed to specify PRIORS =

for

OMEGAs, I found no help. Leonid G. mentions the inverse Wishart matrix =

in

his historic contributions to NMusers, but again I could not find out =

how to

obtain it. If it does not happen in NONMEM, is there a tool in R that =

can

give me that matrix?

Your help is greatly appreciated,

Joachim

Joachim Grevel, PhD

Scientific Director

BAST Inc Limited

BioCity Nottingham

Pennyfoot Street

Nottingham, NG1 1GF

Tel: +44 (0)115 8120497

Received on Fri Feb 24 2012 - 07:37:06 EST

Date: Fri, 24 Feb 2012 12:37:06 -0000

Dear all,

The NONMEM control file of Example 1 in the USERs GUIDE to NONMEM 7.2 =

pp.

108/128 tells us how to work with priors:

; Prior information to the OMEGAS (NETPxNETP of them).

$OMEGA BLOCK(4)

0.2 FIX

0.0 0.2

0.0 0.0 0.2

0.0 0.0 0.0 0.2

; Degrees of freedom to prior OMEGA matrix (1 for each Omega Prior =

block).

; Because degrees of freedom is very low, equal to the

; the dimension of the prior OMEGA, this means that the prior =

information to

the OMEGAS is

; highly uninformative

$THETA (4 FIX)

This is what I use with NONMEM 7.2

; when I follow the instruction and use inverse Wishart to represent the

OMEGA of my previous NONMEM analysis (2500 conc in 200 patients).

$OMEGA BLOCK(2)

0.000135 FIX

0.0000195 0.000640

; I want to make the priors informative and calculated df according to =

the

proposal by Mats.

$THETA (138 FIX)

; when I do not follow the instruction and use simply the covariance =

matrix

of the previous NONMEM analysis of the large data file:

$OMEGA BLOCK(2)

0.000131 FIX

0.0000191 0.000627

$THETA (138 FIX)

There is not really a big difference in my example.

Joachim

Joachim Grevel, PhD

Scientific Director

BAST Inc Limited

BioCity Nottingham

Pennyfoot Street

Nottingham, NG1 1GF

Tel: +44 (0)115 8120497

From: owner-nmusers

On

Behalf Of Stephen Duffull

Sent: 22 February 2012 17:46

To: Mats Karlsson; 'Joachim Grevel'; 'Coen van Hasselt'; 'nmusers'

Subject: RE: [NMusers] OMEGA priors using modes of inverse Wishart =

matrix

Hi

An appropriate value for dof of the IW is difficult to determine. While =

it

can be set at n-1 from a prior this is somewhat arbitrary. It is not in

this sense like a t-distn where we calculate dof in this manner.

You would have to get a feeling for the degree of spread in your =

deviates

given your guess at OMEGA(0) and dof. This can be done by simulation or =

in

special circumstances by direct calculation.

Steve

--

From: owner-nmusers

On

Behalf Of Mats Karlsson

Sent: Thursday, 23 February 2012 3:58 a.m.

To: 'Joachim Grevel'; 'Coen van Hasselt'; 'nmusers'

Subject: RE: [NMusers] OMEGA priors using modes of inverse Wishart =

matrix

Dear Joachim,

The IW distribution is not something you get from NONMEM, you have to =

give

the degrees of freedom of the IW prior distribution. Normally this is at =

or

below the number of subjects in you previous study depending the =

information

about the parameter per subject.

In addition to User’s Guides, you may find useful info in Gisleskog et =

al J

Pharmacokinet Pharmacodyn. 2002 Dec;29(5-6):473-505.

Best regards,

Mats

Mats Karlsson, PhD

Professor of Pharmacometrics

Dept of Pharmaceutical Biosciences

Faculty of Pharmacy

Uppsala University

Box 591

75124 Uppsala

Phone: +46 18 4714105

Fax + 46 18 4714003

From: owner-nmusers

On

Behalf Of Joachim Grevel

Sent: 22 February 2012 15:24

To: 'Coen van Hasselt'; nmusers

Subject: RE: [NMusers] OMEGA priors using modes of inverse Wishart =

matrix

Dear Coen,

There I do have the answer: with MCMC Bayesian in NONMEM 7.1 you have to =

use

NWPRI according to the guide.

Dear Nidal,

What I try to do is that: use an existing very well defined popPK model

(2500 conc in 200 patients) to obtain individual PK parameters in only =

20

additional patients that have sparse sampling (2 to 4 conc per patient). =

I

was planning to use informative priors rather than add 80 conc to a =

bulk of

2500 conc. What do you think?

Thanks to all, specifically Tim!

Joachim

From: Coen van Hasselt [mailto:Coen.vanHasselt

Sent: 22 February 2012 14:03

To: jgrevel

Subject: Re: [NMusers] OMEGA priors using modes of inverse Wishart =

matrix

Dear Joachim,

I have always wondered about this particular question myself as well..

Thanks for asking at NMusers.

Another thing related to the PRIORs I was wondering about: you can =

either

use NWPRI (i.e. with the inverse wishart for OMEGA's), or TNPRI, which =

uses

a multivariate normal for the OMEGA's. Do you have any idea when to use

either of these two possible implementations ?

Thanks,

Coen

Dear NMusers,

Our NONMEM User Guides are full of good advice and they are searchable. =

Yet

when I tried to find out whether any of the estimation methods could be

enticed to give me the ?inverse Wishart matrix? needed to specify PRIORS =

for

OMEGAs, I found no help. Leonid G. mentions the inverse Wishart matrix =

in

his historic contributions to NMusers, but again I could not find out =

how to

obtain it. If it does not happen in NONMEM, is there a tool in R that =

can

give me that matrix?

Your help is greatly appreciated,

Joachim

Joachim Grevel, PhD

Scientific Director

BAST Inc Limited

BioCity Nottingham

Pennyfoot Street

Nottingham, NG1 1GF

Tel: +44 (0)115 8120497

Received on Fri Feb 24 2012 - 07:37:06 EST