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: [email protected] "Elodie Plan" <[email protected]> Sent by: [email protected] 04/03/2010 14:33 To <[email protected]>, <[email protected]> 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: [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. Andreas Lindauer Pharmacokineticist Pharmacokinetics and Metabolism R&D Center. Ferrer Internacional S.A. Juan de Sada 32, 08028 Barcelona [email protected] www.ferrergrupo.com ¿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. This message and any attachment are confidential and may be privileged or otherwise protected from disclosure. If you are not the intended recipient, you must not copy this message or attachment or disclose the contents to any other person. If you have received this transmission in error, please notify the sender immediately and delete the message and any attachment from your system. Merck KGaA, Darmstadt, Germany and any of its subsidiaries do not accept liability for any omissions or errors in this message which may arise as a result of E-Mail-transmission or for damages resulting from any unauthorized changes of the content of this message and any attachment thereto. Merck KGaA, Darmstadt, Germany and any of its subsidiaries do not guarantee that this message is free of viruses and does not accept liability for any damages caused by any virus transmitted therewith. Click http://disclaimer.merck.de to access the German, French, Spanish and Portuguese versions of this disclaimer.
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