Re: Rich data set
From: "David Nix, Pharm D." <nix@pharmacy.arizona.edu>
Subject: Re: Rich data set
Date: Mon, 14 May 2001 14:38:42 -0700
Thanks Leonid Gibiansky for your suggestion. I tried the following control stream:
$PROBLEM POPULATION DATA
$INPUT ID PERD TX SEQ DOSE=AMT ATIM TIME DV AGE SEX RACE SMOK
$INPUT HT WT BMI LBW CLCR
$DATA CLOFAZ3.PRN
$SUBROUTINES ADVAN2 TRANS2
$PK
TVKA=THETA(1)
TVCL=THETA(2)
TVV=THETA(3)
KA=TVKA*EXP(ETA(1))
CL=TVCL*EXP(ETA(2))
V=TVV*EXP(ETA(3))
S2=V
ALAG1=THETA(4)*EXP(ETA(4))
F1=1
IF(TX.EQ.2) F1=THETA(5)
IF(TX.EQ.3) F1=THETA(6)
IF(TX.EQ.3) F1=THETA(7)
$ERROR
IPRED=F
Y=IPRED*(1+EPS(1))+EPS(2)
$THETA (0,1.0) (0,202) (0,1270) (0,2)
$THETA (0,1.5) (0,1) (0,.94)
$OMEGA 0.25 0.25 0.25 0.25
$ESTIMATION METHOD=1 INTERACTION POSTHOC MAXEVAL=9000 NOABORT
$COVR
The error message was:
0MINIMIZATION TERMINATED
DUE TO PROXIMITY OF LAST ITERATION EST. TO A VALUE
AT WHICH THE OBJ. FUNC. IS INFINITE (ERROR=136)
0AT THE LAST COMPUTED INFINITE VALUE OF THE OBJ. FUNCT.:
ERROR IN NCONTR WITH INDIVIDUAL 5 ID= .50000000E+01
NUMERICAL HESSIAN OF OBJ. FUNC. FOR COMPUTING CONDITIONAL ESTIMATE
IS NON POSITIVE DEFINITE
THETA=
2.48E-01 7.80E+01 5.27E+03 1.44E+00 1.32E+00 1.00E+00
2.15E+02
NO. OF FUNCTION EVALUATIONS USED: 1131
NO. OF SIG. DIGITS UNREPORTABLE
ETABAR IS THE ARITHMETIC MEAN OF THE ETA-ESTIMATES,
AND THE P-VALUE IS GIVEN FOR THE NULL HYPOTHESIS THAT THE TRUE MEAN IS
0.
ETABAR: .35E+00 .83E+00 -.70E+00 -.62E+00
P VAL.: .13E-01 .65E-01 .11E+00 .10E-02
The error made be think about a possible data coding problem
ID PERD TX SEQ DOSE=AMT TIME DV AGE SEX RACE SMOK HT WT BMI LBW CLCR
Originally I had:
ID =1, Tx=1, dose=200 then several lines for concentrations
ID =1, Tx=2, dose=200 then several lines for concentrations.
ID =1, Tx=3, dose=200 then several lines for concentrations
....
This did not work since the times were interpreted out of sequence - so I provided a single dose then
time 1, Tx 1, conc
time 1, Tx 2, conc
time 1, Tx 3, conc
time 1, Tx 4, conc
......
I then recoded data with new times: (note two weeks washout between doses)
Tx provided during period 1 = time
Tx provided during period 2 = time + 336
Tx provided during period 3 = time + 672
Tx provided during period 4 = time + 1008
After fixing the data set and re running some of my previous control streams, I got the program to run without errors.