RE: [NMusers] NONLINEAR PK MODEL ERROR

[Mark Sale - Next Level Solutions]

Yuhong,   You likely have a predicted value of 0 at some point  (maybe a predose sample?).  With a predicted value of 0, the proportional error variance will be 0, and you have the additive error variance fixed to 0.  So, the total error variance will be zero.  Since the "weight" for the sum of squares is the error variance, and this appears in the denominator of the calculation of the sum of weighted squared deviations, you're getting an infinite sum of squares.  You might consider not fixing the additive error variance to 0. Mark Mark Sale MD President, Next Level Solutions, LLC www.NextLevelSolns.com 919-846-9185 A carbon-neutral company See our real time solar energy production at: http://enlighten.enphaseenergy.com/public/systems/aSDz2458 -------- Original Message -------- Subject: [NMusers] NONLINEAR PK MODEL ERROR From: Yuhong Chen <chen.yuhong2...@gmail.com> Date: Mon, February 13, 2012 4:20 pm To: nmusers@globomaxnm.com Dear nmusers,   I have a compound with nonlinear CL. I tried to run the nonlinear model but got error message as following, could someone point out what could be the error in my control file or my data? Best regards,   Yuhong 0PROGRAM TERMINATED BY OBJ ERROR IN CELS WITH INDIVIDUAL 1 ID= 1.00000000000000E+00 SUM OF "SQUARED" WEIGHTED INDIVIDUAL RESIDUALS IS INFINITE MESSAGE ISSUED FROM ESTIMATION STEP AT INITIAL OBJ. FUNCTION EVALUATION My control file is $INPUT ID STUD STYP DOSE AMT EVID MDV TIME DV HEIG WT BMI AGE SEX RACE $DATA ../data/M_PK.NM.csv IGNORE=# $SUBROUTINE ADVAN6 TRANS1 TOL=3 $MODEL NCOMP=3  COMP=(DEPOT DEFDOSE)  COMP=(CENT DEFOBS)  COMP=(PERIPH) $PK ALAG1 = THETA(1) KA = THETA(2) V2 = THETA(3) Q = THETA(4) V3 = THETA(5) TVM = THETA(6) KM = THETA(7) ;#################################################################### ; Define IIV parameters ;ZLAG = ETA(1) ;ZKA = ETA(2) ;ZV2 = ETA(3) ;ZQ3 = ETA(4) ;ZV3 = ETA(5) ZVM = ETA(1) ;ZKM = ETA(3) ;######################################################################## ; NONMEM PK Parameter Definitions VM = TVM*EXP(ZVM) ;KM = TKM*EXP(ZKM) ;V2 = TV2*EXP(ZV2) ;Q = TQ3*EXP(ZQ3) ;V3 = TV3*EXP(ZV3) ;KA = TKA*EXP(ZKA) ;ALAG1 = TLAG*EXP(ZLAG)   S2 = V2/1000 ;########################################################################### $DES   ; PK Model   CP = A(2)/S2   DADT(1) = - KA*A(1)   DADT(2) = KA*A(1) - Q/V2*A(2) + Q/V3*A(3) - CP*VM/(KM+CP)   DADT(3) = Q/V2*A(2) - Q/V3*A(3) ;########################################################################### $ERROR Y = F + F*EPS(1)+EPS(2) IPRE = F   ;########################################################################## ; SECONDARY PARAMETERS ;########################################################################## $THETA (0,1)   ; ALAG1 [hr] (0,4)     ; KA [1/hr] (0,4)     ; V2 [L] (0,0.1)   ; Q3 [L/hr] (0,10)   ; V3 [L] (0,100)  ; VM [ng/mL/hr] (0,10)   ; KM [ng/mL] $OMEGA ;0.5     ; ZLAG ;0 FIX   ; ZKA ;0 FIX   ; ZV2 ;0 FIX   ; ZQ3 ;0 FIX   ; ZV3 0.5     ; ZVM ;0.5     ; ZKM $SIGMA 0.02    ; Proportional 0 FIX ; Additive [ug/mL] $EST PRINT=20 MAXEVAL=9999 POSTHOC NOABORT METHOD=1 POSTHOC INTER MSF=MSFO.msf $COV MATRIX=S PRINT=E $TABLE ID TIME IPRE EVID MDV AMT DV ALAG1 VM KM V2 V3 Q KA ZVM STUD DOSE AGE WT BMI SEX RACE NOPRINT ONEHEADER FILE=nmout.tab