AW: Meta-analysis with Nonmem

Dear Leonid, Andreas, I would suggest to simulate each study with N subjects based on the known distribution, mean value (DV), SD,N. This would consider the number of subjects in each study as well as the study specific variability. The datasets can be merged and used for a combined NONMEM analysis If the number of subjects in a study is small, it might be useful to repeat the simulation and produce different combined datasets The NONMEM results based on all combined datasets can be compared/analyzed Best regards Dirk Dirk Garmann, PhD Clinical Scientific Expert /Pharmacokineticist Merz Pharmaceuticals Eckenheimer Landstrasse 100 60318 Frankfurt Phone +49 (69) 1503 720 -----Ursprüngliche Nachricht----- Von: [email protected] [mailto:[email protected]] Im Auftrag von Leonid Gibiansky Gesendet: Wednesday, February 24, 2010 4:45 PM An: [email protected] Cc: [email protected] Betreff: Re: [NMusers] Meta-analysis with Nonmem Andreas, I think if you have only study-level data, you can treat each study as a "subject", build meta-population dose-PD model in the usual way, IPRED=Emax (or some other) function of DOSE and modify the error part as follows: For each data point, you know the mean value (DV), SD, and N. From SD and N you can get an estimate of standard error of the mean as SE=SD/sqrt(N) (computed for each data point and included into the data file). Then your error model would include Y=IPRED+SE*EPS(1) I am not sure whether you need to fix SIGMA $SIGMA 1 FIXED ; for EPS(1) thus assuming that all error in your model comes from the "assay", or estimate it thus allowing for unexplained model misspecification and extra error. I would try both ways to see the difference. This is the simplest version that can be further improved (? or at least, made more complicated) by adding the study effect on error (thus accounting for possible differences in study populations; Y=IPRED+SE*EXP(ETA(1))*EPS(1)), etc. 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: > > Dear NMUSERS, > > I wanted to investigate the dose-response relationship (Emax model) of a > drug with NONMEM, based on data from literature (i.e. a meta-analysis). > However, I am not quite sure how to deal with the different levels of > random effects. Suppose I have 10 studies of different size where > different doses were given and the response is presented as average > change of a biomarker +/- standard deviation for each dose level. How > would I incorporate the standard deviation of the biomarker measurements > reported in each study for each dose level and how would I account for > the different number of patients in the study? > I would greatly appreciate your help, maybe with a NM-code snippet or > reference to a paper where something similar has been done. > > Thanks in advance, 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? 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