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 


[email protected] 
www.ferrergrupo.com 







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