Sequential PD model parameter stays at initial estimation problem
Hi Dear NMusers,
I have a sequential PD model and I listed the code here. base is the
baseline level of the PD parameter for each individual and was included in
the dataset. The problem with this code is that my only parameter to be
estimated Vmax stays at the initial estimation whatever I provide and the
gradient for THETA1 stays at 0 from the beginning. And the run time is
extremely long. If I change F4 to another THETA to be estimated, the same
problem still exists.
Will anyone please shed some light on this problem?
Thanks a lot!
Lei
$PROBLEM PD model
$INPUT ID ETACL ETAV2 ETAKA Weight AMT DV TIME STUDY base CMT
$DATA PD.csv IGNORE=@ WIDE
$SUBROUTINES ADVAN6 TOL=3
$MODEL NCOMP=4
COMP=GUT COMP=CENTRAL COMP=PERI COMP=EFFECT
;---------------
$PK SCALE = Weight
SCALE2 = Weight ** 0.75 ; allometric
THETACL=1 ; L/day
THETAV1= 1; L/kg
THETACLRA= 1 ; L/day
THETAV2=1 ; L/kg
THETAKA= 1 ; 1/day
THETAALAG1= 1 ;days
THETAF1= 1
THETACLHILL= 1
THETACLTITER= 1
THETACLRAHILL= 1
CL = SCALE2 * THETACL * EXP(ETACL)
V1 = SCALE * THETAV1
CLRA = SCALE2 * THETACLRA
V2 = SCALE * THETAV2 * EXP(ETAV2)
KA = THETAKA * EXP(ETAKA)
ALAG1 = THETAALAG1
F1 = THETAF1
S2=V1
Vmax= THETA(1)* EXP(ETA(1))
Km = 100
F4=base ; R0 is the baseline for each individual
K = CL / V1
K23 = CLRA / V1
K32 = CLRA / V2
$DES DADT(1)= -KA * A(1)
DADT(2)= (KA * A(1)) - ((K + K23) * A(2)) + (K32 * A(3))
DADT(3)= K23 * A(2) - K32 * A(3)
CP= A(2)/S2
DADT(4)= -Vmax*CP*A(4)/(Km+A(4))
$ERROR
IPRED=F
Y= A(4)*(1+ERR(1))+ERR(2)
;---------------
$THETA (0,10)
$OMEGA (0 FIXED)
$SIGMA 0.1 10
;---------------
$EST METHOD=0 MAXEVAL=9999 NOABORT PRINT=5
$COVARIANCE