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RE: The Standard Two-Stage and ELS

From: Mats Karlsson <mats.karlsson>
Date: Tue, 3 Mar 2009 18:57:40 +0100

Dear Kim,

Using your model and data file (with ID in $INPUT results in the desired
estimation. See TABLE from lst file:

 
****************************************************************************
********************************************
 ********************
********************
 ******************** TABLES OF DATA AND
PREDICTIONS ********************
 ********************
********************
 
****************************************************************************
********************************************
 
1TABLE NO. 1



 LINE NO. SUB TIME CL V DV PRED RES
WRES
 
    1
+ 1.00E+00 0.00E+00 5.03E+00 4.97E+01 0.00E+00 6.50E+02
0.00E+00 0.00E+00
 
    2
+ 1.00E+00 1.00E+00 5.03E+00 4.97E+01 9.80E+01 5.88E+02
-4.90E+02 -7.81E-02
 
    3
+ 1.00E+00 2.00E+00 5.03E+00 4.97E+01 8.20E+01 5.32E+02
-4.50E+02 -7.29E-02
 
    4
+ 1.00E+00 4.00E+00 5.03E+00 4.97E+01 5.80E+01 4.36E+02
-3.78E+02 -6.00E-02
 
    5
+ 1.00E+00 8.00E+00 5.03E+00 4.97E+01 3.30E+01 2.92E+02
-2.59E+02 -3.47E-02
 
    6
+ 1.00E+00 1.20E+01 5.03E+00 4.97E+01 2.20E+01 1.96E+02
-1.74E+02 -1.64E-02
 
    7
+ 1.00E+00 1.50E+01 5.03E+00 4.97E+01 1.70E+01 1.45E+02
-1.28E+02 -6.71E-03
 
    8
+ 1.00E+00 2.00E+01 5.03E+00 4.97E+01 1.20E+01 8.80E+01
-7.60E+01 5.01E-03
 
    9
+ 1.00E+00 3.00E+01 5.03E+00 4.97E+01 7.50E+00 3.24E+01
-2.49E+01 1.96E-02
 
   10
+ 1.00E+00 4.50E+01 5.03E+00 4.97E+01 3.70E+00 7.22E+00
-3.52E+00 2.99E-02
 
   11
+ 1.00E+00 6.00E+01 5.03E+00 4.97E+01 1.80E+00 1.61E+00
1.89E-01 3.57E-02
 
   12
+ 1.00E+00 7.00E+01 5.03E+00 4.97E+01 1.20E+00 5.93E-01
6.07E-01 4.21E-02
 
   13
+ 2.00E+00 0.00E+00 5.27E+00 4.74E+01 0.00E+00 6.50E+02
0.00E+00 0.00E+00
 
   14
+ 2.00E+00 1.00E+00 5.27E+00 4.74E+01 1.01E+02 5.88E+02
-4.87E+02 -7.75E-02
 
   15
+ 2.00E+00 2.00E+00 5.27E+00 4.74E+01 8.50E+01 5.32E+02
-4.47E+02 -7.24E-02
 
   16
+ 2.00E+00 4.00E+00 5.27E+00 4.74E+01 5.70E+01 4.36E+02
-3.79E+02 -6.02E-02
 
   17
+ 2.00E+00 8.00E+00 5.27E+00 4.74E+01 3.30E+01 2.92E+02
-2.59E+02 -3.46E-02
 
   18
+ 2.00E+00 1.20E+01 5.27E+00 4.74E+01 2.20E+01 1.96E+02
-1.74E+02 -1.64E-02
 
   19
+ 2.00E+00 1.50E+01 5.27E+00 4.74E+01 1.70E+01 1.45E+02
-1.28E+02 -6.64E-03
 
   20
+ 2.00E+00 2.00E+01 5.27E+00 4.74E+01 1.20E+01 8.80E+01
-7.60E+01 5.12E-03
 
   21
+ 2.00E+00 3.00E+01 5.27E+00 4.74E+01 7.50E+00 3.24E+01
-2.49E+01 1.98E-02
 
   22
+ 2.00E+00 4.50E+01 5.27E+00 4.74E+01 3.70E+00 7.22E+00
-3.52E+00 3.06E-02
 
   23
+ 2.00E+00 6.00E+01 5.27E+00 4.74E+01 1.80E+00 1.61E+00
1.89E-01 3.74E-02


Best regards,
Mats

Mats Karlsson, PhD
Professor of Pharmacometrics
Dept of Pharmaceutical Biosciences
Uppsala University
Box 591
751 24 Uppsala Sweden
phone: +46 18 4714105
fax: +46 18 471 4003


-----Original Message-----
From: owner-nmusers
Behalf Of Kristensen, Kim
Sent: Tuesday, March 03, 2009 5:36 PM
To: Brian M. Sadler; nmusers
Subject: RE: [NMusers] The Standard Two-Stage and ELS

Dear Brian
Thanks for the suggestion. I've tried changing the ID and the first row to
EVID=1. However, the posthoc (ELS) modelling of data, as suggested by Dr's
Beal and Shafer, dosn't seem to go through as the parameter are all left
unchanged i.e. as initial estimates!

/Kim

-----Original Message-----
From: Brian M. Sadler [mailto:bsadler1
Sent: den 3 mars 2009 12:49
To: Kristensen, Kim; nmusers
Subject: RE: [NMusers] The Standard Two-Stage and ELS


Dear Kim,

There is no ID variable in the $INPUT statement. Try:

$INPUT SUB=ID AMT TIME DV EVID CMT MDV

Cheers... Brian


Brian M. Sadler, Ph.D.
Strategic PK Consulting, LLC
1209 Seabrook Avenue
Cary, North Carolina 27511
USA
bsadler1
+1 (919) 523-5485 (mobile)
+1 (508) 408-0250 (fax)



-----Original Message-----
From: owner-nmusers
Behalf Of Kristensen, Kim
Sent: Tuesday, March 03, 2009 4:26 AM
To: nmusers
Subject: [NMusers] The Standard Two-Stage and ELS

Dear user

Searching the user site I found a pre-published method by Dr's Beal and
Shafer (link given below) to do The Standard Two-Stage Estimation using ELS
with NONMEM. Out of curiosity I tried it, but I could not get it to work
with NM6. Could anyone tell what I do wrong?? Control stream and test data
are given below.
<http://www.cognigencorp.com/nonmem/nmo/topic035.html>

$PROBLEM Standard two stage
$INPUT SUB AMT TIME DV EVID CMT MDV
$DATA ASA_NM3.txt IGNORE=#
$SUBROUTINE ADVAN1 TRANS2
$PK
CL=THETA(1)*EXP(ETA(1))
V =THETA(2)*EXP(ETA(2))
$ERROR
Y=F+F*EXP(ETA(3))*ERR(1)
$THETA 5 50 ;these are rough typical population
values
$OMEGA 100 100 100
$SIGMA 1 FIXED
$ESTIMATION MAXEVAL=0 POSTHOC METH=COND INTERACTION
$TABLE SUB TIME CL V

# SUB AMT TIME DV EVID CMT MDV
       1 650 0 0 4 1 1
       1 . 1 98 . 1 0
       1 . 2 82 . 1 0
       1 . 4 58 . 1 0
       1 . 8 33 . 1 0
       1 . 12 22 . 1 0
       1 . 15 17 . 1 0
       1 . 20 12 . 1 0
       1 . 30 7.5 . 1 0
       1 . 45 3.7 . 1 0
       1 . 60 1.8 . 1 0
       1 . 70 1.2 . 1 0
       2 650 0 0 4 1 1
       2 . 1 101 . 1 0
       2 . 2 85 . 1 0
       2 . 4 57 . 1 0
       2 . 8 33 . 1 0
       2 . 12 22 . 1 0
       2 . 15 17 . 1 0
       2 . 20 12 . 1 0
       2 . 30 7.5 . 1 0
       2 . 45 3.7 . 1 0
       2 . 60 1.8 . 1 0
       2 . 70 1.1 . 1 0


________________________________
Kim Kristensen, M.Sc(pharm),Ph.D.
Pharmacokineticist,
Clinical Pharmacology & DMPK
Medical Science Sweden
AstraZeneca R&D Lund
SE-221 87 Lund, Sweden
Tel: +46 46 33 86 63 Fax: +46 46 336110
> Mobil: +46 (0) 705 33 77 18
> e-mail: kim.kristensen
________________________________


Received on Tue Mar 03 2009 - 12:57:40 EST

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