RE: Meta-analysis with Nonmem

From: [email protected] [mailto:[email protected]] On Behalf Of [email protected] Sent: den 4 mars 2010 16:21 To: Elodie Plan Cc: [email protected] Subject: RE: [NMusers] Meta-analysis with Nonmem Hi Elodie, Martin and Mats, Thanks for your suggestion, a very interesting approach. So, THETA1 would give me an estimate of the global between patient variability, expressed as SD, across all studies and OMEGA1 would be an estimate of the between study variability (BSV) of this SD. OMEGA2 would be the BSV of the average response. Is this interpretation correct? I suppose the number of studies has to be quite large to get precise estimates of the BSV. 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. 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"Elodie Plan" <[email protected]> 04/03/2010 14:33 Para <[email protected]>, <[email protected]> cc Asunto 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. Ferrer Andreas Lindauer Pharmacokineticist Pharmacokinetics and Metabolism R&D Center. Ferrer Internacional S.A. Juan de Sada 32, 08028 Barcelona <mailto:[email protected]> [email protected] http://www.ferrergrupo.com/ 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. <<image001.gif>> <<image002.gif>>