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Re: Meta-analysis with Nonmem

From: Leonid Gibiansky <LGibiansky>
Date: Fri, 26 Feb 2010 08:19:22 -0500

I am not sure that I understood your idea


What is ETA(1)? It would be added to the model part, with the new
prediction being:


As to the code


it will be interpreted correctly (make sure you use INTERACTION option).
Linearization is done for the EPS() part, and the function above is
linear over EPS.

If SIGMA is not fixed, you treat the entire combination
SE^2*SIGMA(1,1) as the variance (study-specific or even point-specific)
of the residual error, with SE being the weighting function that takes
care about differences in the number of patients and the variability of
the patient population (between study and/or points).


Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
e-mail: LGibiansky at
tel: (301) 767 5566

> Thank you Leonid and Dirk for your replies. They were very helpful.
> Leonid, what would you think about the following:
> 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
> alindauer-research
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Received on Fri Feb 26 2010 - 08:19:22 EST

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