Modeling of inter study variability (ISV) as a third random effect level

From: "Harnisch, Lutz, HMR/DE" <Lutz.Harnisch@hmrag.com> Subject: Modeling of inter study variability (ISV) as a third random effect level Date: Mon, 31 May 1999 16:21:28 +0200 I don't know how to implement into NONMEM the model of a third random effect level, like ISV. Sampling individual ETA's from an additional OMEGA-element and allocating those for individual studies didn't work. I don't know how to maintain the individual ETA from one individual to the next within a single study. And furthermore how to get a new ETA for the first record of the next study. Therefore I tried a different approach: to sample all study ETA's at NEWIND.EQ.0 (i.e. at the first record in the dataset) with $OMEGA BLOCK(1) 0.1 ; first sub study ETA(1) $OMEGA BLOCK(1) SAME ; sec study ETA(2) ... $OMEGA BLOCK(1) SAME ; last substudy ETA(n) and allocated them as factors for instance on CL by IF (NEWIND.EQ.0) THEN IS01 = EXP(ETA(1)) IS02 = EXP(ETA(2)) ... ISn = EXP(ETA(n)) ENDIF FCL = 1 IF (STUD.EQ.ST01) THEN FCL = IS01 ELSIF (STUD.EQ.ST02) THEN FCL = IS02 ... ENDIF CL = THETA(x) * FCL But the coding above causes all the gradients for the PK-model to be zero, even if I fix ETA(1) to zero, which means for my understanding that, all factors should become 1, and therefore, the gradients should be different from zero. I really like to know if coding of ISV with NONMEM is possible, any help would be highly appreciated regards Lutz Harnisch Hoechst Marion Roussel | Product Realization | Biodynamics ( http://popkin.fra.hmrag.com/) Building H840 | Room 449 | D-65926-Frankfurt-Main | Germany phone +49-69-305-16481 | fax +49-69-305-81990 | mailto:lutz.harnisch@hmrag.com