NONMEM Users Network Archive

Hosted by Cognigen

RE: Meta-analysis with Nonmem

From: marco.campioni
Date: Fri, 5 Mar 2010 13:41:26 +0100

Dear Elodie,

Thank you for your example.

Could you please further comment on why you used the same EPS(1) for
fitting both AV and SD instead of writing:

IF(FLAG.EQ.0) THEN
Y = SD+SESD*EPS(1)
ELSE
Y = AV+SEAV*EPS(2)
ENDIF
 
$SIGMA 1 FIX
$SIGMA 1 FIX

Many thanks

Ciao

Marco

------------------------------------------------------------------------------
Marco Campioni, PhD
Modelling & Simulations
Exploratory Medicine

Merck Serono S.A. - Geneva
9, Chemin des Mines
1202 Geneva, Switzerland
Location: B1.4
Phone: +41 22 414 4554
Fax: +41 22 414 3059
Email: marco.campioni



"Elodie Plan" <elodie.plan
Sent by: owner-nmusers
04/03/2010 14:33

To
<alindauer-research m.com>
cc

Subject
RE: [NMusers] Meta-analysis with Nonmem






Dear Andreas,
 
An approach you may consider is to model both the standard deviation and
the average as dependent variables:
 
SD=THETA(1)*EXP(ETA(1))
AV=(THETA(2)+DOSE*THETA(3))*EXP(ETA(2))
 
SESD=SD/(2*(N-1)**.5)
SEAV=SD/N**.5
 
IF(FLAG.EQ.0) THEN
Y = SD+SESD*EPS(1)
ELSE
Y = AV+SEAV*EPS(1)
ENDIF
 
$SIGMA 1 FIX
 
Your dataset would treat study as individuals, include N the number of
individuals in the study arm and incorporate a flag, so would look like:
STUD=ID DV N FLAG DOSE
1 SD1 N1 0 D1
1 AV1 N1 1 D1
1 SD2 N2 0 D2
1 AV2 N2 1 D2

 
Note: this is only valid when there was only 1 endpoint per subject.
Hope this helps.
 
Best regards,
Elodie, Martin and Mats
 
Elodie L. Plan, PharmD, MSc, PhD student
********************************************
Uppsala Pharmacometrics Research Group,
Department of Pharmaceutical Biosciences,
P.O. Box 591, SE-751 24 Uppsala, SWEDEN
Office +46 18-471 4385, Fax +46 18-471 4003
 
From: owner-nmusers xnm.com [mailto:owner-nmusers
On Behalf Of alindauer-research
Sent: Friday, February 26, 2010 10:26 AM
To: nmusers
Subject: Re: [NMusers] Meta-analysis with Nonmem
 

Thank you Leonid and Dirk for your replies. They were very helpful.

Leonid, what would you think about the following:
Y=IPRED+SE*EPS(1)+ETA(1)
With SIGMA fixed to 1 and OMEGA being the inter-study standard-deviation?
What would be the interpretation of SIGMA if it were not fixed to 1?
You wrote:
>>Y=IPRED+SE*EXP(ETA(1))*EPS(1)), etc.
Wouldn't this be somehow transformed by NONMEM because of the
linearization process? Similarly to why we cannot use the exponential
residual error model directly in NONMEM, but have to do the
transform-both-sides approach.

Dirk, good idea. However, estimation of the simulated datasets might
become very time consuming when you combine data from several large
studies. And, as you said:
>> If the number of subjects in a study is small, it might be useful to
repeat the simulation and produce different combined datasets.
I would even go further and say, that it is absolutly necessary to repeat
the simulation-reestimation procedure many times in order to get "stable"
results.

Best regards, Andreas.


Andreas Lindauer
Pharmacokineticist
Pharmacokinetics and Metabolism
R&D Center. Ferrer Internacional S.A.
Juan de Sada 32, 08028 Barcelona


alindauer-research ferrergrupo.com
www.ferrergrupo.com





 


¿Necesita imprimir este mensaje? Protejamos el medio ambiente.
Li cal imprimir aquest missatge? Protegim el medi ambient.
Do you need to print this message? Let's protect the environment.
 

Este mensaje, y en su caso, cualquier fichero anexo al mismo, puede
contener información confidencial, siendo para uso exclusivo del
destinatario, quedando prohibida su divulgación, copia o distribución a
terceros sin la autorización expresa del remitente. Si Vd. ha recibido
este mensaje erróneamente, se ruega lo notifique al remitente y proceda a
su borrado. Gracias por su colaboración.

This message and its annexed files may contain confidential information
which is exclusively for the use of the addressee. It is strictly
forbidden to distribute copies to third parties without the explicit
permission of the sender. If you receive this message by mistake, please
notify it to the sender and make sure to delete it. Thank you for your
kind cooperation.
 



This message and any attachment are confidential and may be privileged or otherwise protected from disclosure. If you are not the intended recipient, you must not copy this message or attachment or disclose the contents to any other person. If you have received this transmission in error, please notify the sender immediately and delete the message and any attachment from your system. Merck KGaA, Darmstadt, Germany and any of its subsidiaries do not accept liability for any omissions or errors in this message which may arise as a result of E-Mail-transmission or for damages resulting from any unauthorized changes of the content of this message and any attachment thereto. Merck KGaA, Darmstadt, Germany and any of its subsidiaries do not guarantee that this message is free of viruses and does not accept liability for any damages caused by any virus transmitted therewith.

Click http://disclaimer.merck.de to access the German, French, Spanish and Portuguese versions of this disclaimer.

picture
(image/gif attachment: 01-part)

picture
(image/gif attachment: 02-part)

Received on Fri Mar 05 2010 - 07:41:26 EST

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.