RE: NM7.2 SAEM with LIKE

________________________________________ From: [email protected] [[email protected]] on behalf of De Ridder, Filip [JRDBE] [[email protected]] Sent: Wednesday, August 08, 2012 10:06 PM To: Bauer, Robert; [email protected] Subject: [NMusers] RE: NM7.2 SAEM with LIKE Hi Bob, Apparently, Monolix offers two options side by side: mean or mode. However, is there not another difference here: root.phi gives the conditional mean of the sampling-based posterior density, whereas using FNLETA gives you the "classical" EBE, i.e. not sampling based? It seems a bit contradictory that you would use the sampled-based densities to integrate out the ETA's in SAEM to obtain the pop pars, and then not use the sampled-based densities to get the ETA's? Any thoughts are welcome. Kind regards, Filip -----Oorspronkelijk bericht----- Van: Bauer, Robert [mailto:[email protected]] Verzonden: wo 8/08/2012 0:30 Aan: De Ridder, Filip [JRDBE]; [email protected] Onderwerp: RE: NM7.2 SAEM with LIKE Filip: In your case it may be that conditional means are more appropriate than conditional modes, but I would not necessarily conclude that in general. I do not know what Monolix reports regarding individual parameters. Robert J. Bauer, Ph.D. Vice President, Pharmacometrics, R&D ICON Development Solutions 7740 Milestone Parkway Suite 150 Hanover, MD 21076 Tel: (215) 616-6428 Mob: (925) 286-0769 Email: [email protected] Web: http://www.iconplc.com/ ________________________________ From: De Ridder, Filip [JRDBE] [mailto:[email protected]] Sent: Tuesday, August 07, 2012 3:08 PM To: Bauer, Robert; [email protected] Subject: RE: NM7.2 SAEM with LIKE Hi Bob, Thanks for the clarification. Would you agree that the conditional means are more trustworthy, in case there is a relevant difference? In my specific dataset, there are 5 subjects for whom the conditional means yield a much better individual fit, than the "post-hoc" eta's. I believe that in Monolix, the individual parameter estimates are the conditional means, no? In my example Kind regards, Filip -----Oorspronkelijk bericht----- Van: Bauer, Robert [mailto:[email protected]] Verzonden: di 7/08/2012 18:28 Aan: De Ridder, Filip [JRDBE]; [email protected] Onderwerp: RE: NM7.2 SAEM with LIKE Filip: The $TABLE results are obtained from a "post-hoc" assessment at the best fit eta values (modal, EBE), regardless of the method used. To evaluate $TABLE parameters at the conditional mean positions, you may select FNLETA=0. Robert J. Bauer, Ph.D. Vice President, Pharmacometrics, R&D ICON Development Solutions 7740 Milestone Parkway Suite 150 Hanover, MD 21076 Tel: (215) 616-6428 Mob: (925) 286-0769 Email: [email protected] Web: http://www.iconplc.com/ ________________________________ From: [email protected] [mailto:[email protected]] On Behalf Of De Ridder, Filip [JRDBE] Sent: Tuesday, August 07, 2012 10:18 AM To: [email protected] Subject: [NMusers] NM7.2 SAEM with LIKE Dear All, With NM7.2/SAEM, the root.phi output file contains the conditional means (and variances) of the individual phi's (mu(i)+eta(i)) - which is great! I found that the these values can be different from what you get from a $TABLE in more classical way: $PRED MU_1=THETA(1) K=MU_1+ETA(1) ... $TABLE K ... For a some subjects, these are very different, and the ones coming from the $TABLE are clearly less optimal, yielding a bad individual fit, as judged from IPRE calculated in $PRED. I guess one part of the solution is using CPRED and CPREDI - but unfortunately I cannot use these as I (have to) use LIKELIHOOD in $EST (M3 method for BLQ-data). Kind regards, Filip De Ridder Janssen R&D, Beerse, Belgium.