RE: 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
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of [email protected]
Sent: Friday, February 26, 2010 10:26 AM
To: [email protected]
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
[email protected]
www.ferrergrupo.com
Recicla
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