Re: Meta-analysis with Nonmem

Andreas, I am not sure that I understood your idea Y=IPRED+SE*EPS(1)+ETA(1) What is ETA(1)? It would be added to the model part, with the new prediction being: IPRED'=IPRED+ETA(1) As to the code Y=IPRED+SE*EXP(ETA(1))*EPS(1)) 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 -------------------------------------- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web: www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel: (301) 767 5566 [email protected] wrote: > 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 ¿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.