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RE: Meta-analysis with Nonmem

From: Elodie Plan <elodie.plan>
Date: Mon, 8 Mar 2010 15:27:07 +0100

Dear Marco,

 

Actually it does not matter the epsilons of Y(SD) and Y(AV) to be =
sampled from the same distribution, since they are connected to 2 =
observations modeled independently. As you noticed EPS(1) is not =
estimated but fixed, since the magnitude of the variability actually =
comes from the SE multiplication part.

 

Best regards,

Elodie

 

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: marco.campioni
[mailto:marco.campioni
Sent: Friday, March 05, 2010 1:41 PM
To: Elodie Plan
Cc: alindauer-research
owner-nmusers
Subject: RE: [NMusers] Meta-analysis with Nonmem

 


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


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
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.


Ferrer


Andreas Lindauer


Pharmacokineticist


Pharmacokinetics and Metabolism


R&D Center. Ferrer Internacional S.A.


Juan de Sada 32, 08028 Barcelona

        
        

 <mailto:alindauer-research
alindauer-research


 <http://www.ferrergrupo.com/> www.ferrergrupo.com

        
        
        
        
        


  


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Received on Mon Mar 08 2010 - 09:27:07 EST

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