RE: Markov model dataset

Dear Achim, The problem seems to be that you are resetting compartments (CMT= negative value) that you have yet not initialized (CMT=positive value). There might be bigger problems with the code and dataset especially if you are planning to also use it for simulations. To do this I recommend that you at each time point add a dose in each of the 4 compartments (EVID=1 and AMT=1). Then you will use if statements in the model file to set F1, F2, F3 and F4. Based on the previous observation so that the dose actually only enters the relevant compartment. I also recommend that you observations have CMT = 0 and the DV value = to the grade (0,1,2,3) this is also going to be more convenient especially for simulations (I have added some example code below and including code for simulations). The dataset can also be shortened by using a EVID = 4 dose to reset all compartments rather than resetting them 1 by 1. See an example in the bottom of my email. There are multiple ways of doing this I have only described my preferred way of doing it. Best of luck with the modeling! Martin Bergstrand, PhD Pharmacometrics Research Group Dept of Pharmaceutical Biosciences Uppsala University, Sweden Postal address: Box 591, 751 24 Uppsala, Sweden Phone +46 18 471 42 27 Mobile +46 709 994 396 Fax + 46 18 471 40 03 $PK ; << Beginning of $PK code >> IF(NEWIND.NE.2) PSDV = 0 PRSP = PSDV ; Previous DV ; Compartment initialization F1 = 0 F2 = 0 F3 = 0 F4 = 0 IF(PRSP.EQ.0) F1 = 1 ; Initialize compartment 1 if RSPP = 1 (no tox) IF(PRSP.EQ.1) F2 = 1 ; Initialize compartment 2 if RSPP = 2 (grade 1) IF(PRSP.EQ.2) F3 = 1 ; Initialize compartment 3 if RSPP = 3 (grade 2) IF(PRSP.EQ.3) F4 = 1 ; Initialize compartment 4 if RSPP = 4 (grade 3) $ERROR IF(DV.EQ.0.AND.CMT.EQ.0) Y = A(1) IF(DV.EQ.1.AND.CMT.EQ.0) Y = A(2) IF(DV.EQ.2.AND.CMT.EQ.0) Y = A(3) IF(DV.EQ.3.AND.CMT.EQ.0) Y = A(4) ; Cumulative probabilities CUP1 = P1 CUP2 = P1 +P2 CUP3 = P1 +P2 +P3 CUP4 = P1 +P2 +P3 +P4 ; Simulation code IF(ICALL.EQ.4) THEN CALL RANDOM (2,R) IF(R.LE.CUP1) DV = 0 IF(R.GT.CUP1.AND.R.LE.CUP2) DV = 1 IF(R.GT.CUP2.AND.R.LE.CUP3) DV = 2 IF(R.GT.CUP3) DV = 3 ENDIF ; << End of $ERROR code >> PSDV = DV ; Store previous DV ; To activate for simulation ;$SIM (7776) (8877 UNIFORM) ONLYSIM NOPREDICTION << Dataset example >> C ID TIME DOSE DV EVID CMT AMT MDV 0 1 0 0 0 1 1 1 1 0 1 1 50 0 0 0 0 0 0 1 1 50 0 4 1 1 1 0 1 1 50 0 1 2 1 1 0 1 1 50 0 1 3 1 1 0 1 1 50 0 1 4 1 1 0 1 2 50 0 2 0 0 0 0 1 2 50 0 4 1 1 1 0 1 2 50 0 1 2 1 1 0 1 2 50 0 1 3 1 1 0 1 2 50 0 1 4 1 1 0 1 3 50 0 1 0 0 0 0 1 3 50 0 4 1 1 1 0 1 3 50 0 1 2 1 1 0 1 3 50 0 1 3 1 1 0 1 3 50 0 1 4 1 1