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RE: NONLINEAR PK MODEL ERROR

From: Mark Sale - Next Level Solutions <mark>
Date: Mon, 13 Feb 2012 14:56:29 -0700
Yuhong,
 = ; You likely have a predicted value of 0 at some point  (maybe a predo= se sample?).  With a predicted value of 0, the proportional error vari= ance 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 gettin= g an infinite sum of squares.  You might consider not fixing the addit= ive error variance to 0.

Mark

=


Mark Sale MD
President, Next Level So= lutions, LLC
www.NextLevelSoln= s.com
919-846-9185
A carbon-neutral company
See= our real time solar energy production at:


-------- Original Message --------
Subject= : [NMusers] NONLINEAR PK MODEL ERROR
From: Yuhong Chen < To: nmusers uote">
Dear nmusers,
 
I have a compound wi= th nonlinear CL. I tried to run the nonlinear model but got error message a= s 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
SU= M 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)
 COM= P=(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)<= br>;ZKA = ETA(2)
;ZV2 = ETA(3)
;ZQ3 = ETA(4)
;ZV3 = ETA(5= )
ZVM = ETA(1)
;ZKM = ETA(3)
;########################= ################################################
; NONMEM PK Parameter D= efinitions
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
=

;################################################################= ###########
$DES
  ; PK Model
  CP = A(2)/S2
 = DADT(1) = - KA*A(1)
  DADT(2) = KA*A(1) - Q/V2*A(2) + Q/V3*A(3= ) - CP*VM/(KM+CP)
  DADT(3) = Q/V2*A(2) - Q/V3*A(3)
;#= ##########################################################################<= br>$ERROR
Y = F + F*EPS(1)+EPS(2)
IPRE = F
 
;#######= ###################################################################
; SE= CONDARY 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 &n= bsp; ; ZKA
;0 FIX   ; ZV2
;0 FIX   ; ZQ3
;0 FI= X   ; ZV3
0.5     ; ZVM
;0.5  = ;   ; ZKM
$SIGMA
0.02    ; Proportio= nal
0 FIX ; Additive [ug/mL]
$EST PRINT=20 MAXEVAL=9999 P= OSTHOC NOABORT METHOD=1 POSTHOC INTER MSF=MSFO.msf
$COV MATRIX=S P= RINT=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.t= ab

 

=

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Received on Mon Feb 13 2012 - 16:56:29 EST

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