Hi all, I'm having troubles with the following warning message as the prediction for first records weren't right.
######################### (Warning 48) DES-DEFINED ITEMS ARE COMPUTED ONLY WHEN EVENT TIME INCREASES. E. G., DISPLAYED VALUES ASSOCIATED WITH THE FIRST EVENT RECORD OF AN INDIVIDUAL RECORD ARE COMPUTED WITH (THE LAST ADVANCE TO) AN EVENT CREATING MVMODEL ROUTINE ########################## I tried to fit a PKPD model, given PK is a bit complicated, I did in two steps, predicted the PK concentration, then add the concentration column to the dataset for the PD part. Here is the example of the dataset: ID TIME AMT RATE EVID DV LNDV MDV CMT CP 1 0 0 0 0 88 4.477337 0 2 0 1 192.1667 0.52149 0.297994 1 0 0 1 1 0 1 720.1667 0.4448 0.264238 1 0 0 1 1 0.53923 1 1176 0 0 0 16.5 2.80336 0 2 0.77665 Here is the model (kept the dosing records in the datasets but ignore it by setting diff. eqn =0): $DES DADT(1)=0 DRUG=1-IMAX*CP**GAM/(IC50**GAM+CP**GAM) DADT(2)=KIN*DRUG*EXP(BETA*T) - KOUT*A(2) CP2 = CP CA = A(2) But, when I look at the individual prediction, I don't understand why the concentration CP I used to compute inhibition was nonzero in the first record, i.e. CP2, it's different from what is in the dataset. As a result of nonzero concentration, my second data point, still at zero concentration, was a way off (see CA at TIME = 192.17). ID TIME EVID AMT CMT CA CP CP2 KIN MRT KOUT IC50 IMAX GAM DRUG BETA DV 1 0.0000 0.0000 0.0000 2.0000 177.220000 0.0000 0.8556 109.1200 0.2211 0.1306 0.1120 1.0000 1.0000 0.1470 0.0000 88.0000 1 192.1700 1.0000 0.5215 1.0000 838.270000 0.0000 0.0000 109.1200 0.2211 0.1306 0.1120 1.0000 1.0000 1.0000 0.0000 0.0000 1 720.1700 1.0000 0.4448 1.0000 145.570000 0.5392 0.5392 109.1200 0.2211 0.1306 0.1120 1.0000 1.0000 0.1719 0.0000 0.0000 Can anybody point out if there is a problem in my dataset or script or an issue with NONMEM? If latter, would the workaround by forcing DRUG = 1 at TIME = 0 work? Many thanks. Yen Lin
