RE: change calculation of WRES?

Dear Nele, Individual weighted residuals (IWRES) have nothing to do with the parameter estimation in NONMEM. IWRES are calculated and put in table files purely as a diagnostic variable. This way they can be helpful among other things to design a suitable RUV model (and that is what I really think you need to think about) . Normally I would not want to add weighting to different parts of the data based on my expectations. If I anticipated the case of lower residual unexplained variability (RUV) with time I would include such a feature in my RUV model and estimate parameters to describe it (and also evaluate it’s significance). The easiest check to do is to estimate one magnitude of residual error for early samples and one for late (see an example below for a simple additive RUV) . ;--------------------------------------------------------------------------- --------------------------------------------- IF(TIME.LT.X) THEN ; X = Time limit dividing early and late time points W = THETA(x) ; THETA (x) = standard deviation (SD) for RUV of early samples ELSE W = THETA(y) ; THETA (y) = SD for RUV of late samples ENDIF Y = IPRED+W*EPS(1) IRES = DV-IPRED IWRES = IRES/W $SIGMA 1 FIX ; Fixing SIGMA to variance 1 allows us to estimate the scaling factor W on standard deviation scale ;--------------------------------------------------------------------------- --------------------------------------------- I have no experience with a continuous RUV model that describes decreasing RUV with time. If the data is informative enough I sure that it is possible though. An example could look something like this: W0 = THETA(x) ; SD for W at time = 0 W1HL = THETA(y) ; Half-life of time dependent RUV WL = THETA(z) ; SD of non time dependent RUV W1K = LOG(2)/W1HL W1 = (W0- W2) * EXP(-W1K*TIME) W = W1 + WL Y = IPRED+W*EPS(1) $SIGMA 1 FIX ;--------------------------------------------------------------------------- --------------------------------------------- I hope this is of some help to you. Kind regards, Martin Bergstrand, MSc, PhD student ----------------------------------------------- Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Uppsala University ----------------------------------------------- P.O. Box 591 SE-751 24 Uppsala Sweden ----------------------------------------------- <mailto:[email protected]> [email protected] ----------------------------------------------- Work: +46 18 471 4639 Mobile: +46 709 994 396 Fax: +46 18 471 4003