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implementation of prior subroutine

From: nele.kaessner
Date: Fri, 4 Sep 2009 11:15:05 +0200

Dear all,

first of all I would like to thank all the people who took the time to
answer my last question. It really helped understanding the problem.
However, I already have a next problem :-)
I am trying to implement the prior subroutine in NONMEM for a first time,
using NONMEM VI level 1.0. I have created a file named prior.for which
looks the following:

SUBROUTINE PRIOR (ICALL,CNT)
       DOUBLE PRECISION CNT
       NTHETA=6
       NETA=6
       NTHP=6
       NETP=6
       NPEXP=1
       PLEV=0
       CALL NWPRI (NTHETA,NETA,NEPS,NTHP,NETP,NEPP,NPEXP,ITYP,PLEV,
      1 NSAM,ISS,CNT)
       RETURN
       END

When trying to run my model with new data, I get the following error
message:

S:1 .. Fatal Error: Fortran Compilation failed:
FSUBS.f:1:
   SUBROUTINE PRIOR (ICALL,CNT)
   ^
Invalid first character at (^) [info -f g77 M LEX]

 at /usr/share/perl/5.10.0/PsN_2_3_1/nonmem.pm line 27

Can anybody point me to the error? Moreover, I have a question concerning
the prior information on parameter uncertainty. I got an error message
when implementing the values as seen in the NONMEM output file (e.g.
2.22E-05), however when implementing them as presented in the model file
below, I get a problem with the allowed number of digits. How do I get the
correct values in there?

My model file looks like the following:

$PROB PK - Model
$INPUT C ID DOSE AMT ADDL II TIME DV EVID MDV AGE SEX WT
$DATA example.CSV IGNORE=C

$SUBROUTINES PRIOR=../../prior.for
$SUBROUTINES ADVAN4 TRANS4
$PK
   TVA0 = THETA(1)
   ALAG1 = TVA0 * EXP(ETA(1))

   TVK0 = THETA(2)
   KA = TVK0 * EXP(ETA(2))

   TVCL0 = THETA(3)
   CL = TVCL0 * EXP(ETA(3))
 
   TVV20 = THETA(4)
   V2 = TVV20*EXP(ETA(4))

   Q = THETA(5)*EXP(ETA(5))

   V3 = THETA(6)*EXP(ETA(6))

   TVF0 = 1
   F1 = TVF0

   S2=V2/1000
 
   K=CL/V2
   K23=Q/V2
   K32=Q/V3

$ERROR
   W = THETA(13)
   IPRED = LOG(F+1E-10)
   Y=IPRED + W*EPS(1)
   IRES = DV - IPRED
   IWRES = IRES / W

$THETA
         (0.10) ;1 ALAG1
         (0.50) ;2 KA
         (10.0) ;3 CL
         (10.0) ;4 V2
         (20.0) ;5 Q
         (100) ;6 V3
         (0, 0.25) ;7 CV

$OMEGA DIAGONAL(4)
   0.10 ; VAR(ALAG1)
   0.10 ; VAR(KA)
   0.10 ; VAR(CL)
   0.10 ; VAR(V2)
$OMEGA BLOCK(2)
   0.10 ; VAR(Q)
   0.010 0.10 ; VAR(V3)
$SIGMA 1 FIXED

$THETA 0.1 FIX ;prior on ALAG
$THETA 0.5 FIX ;prior on KA
$THETA 10 FIX ;prior on CL
$THETA 10 FIX ;prior on V2
$THETA 20 FIX ;prior on Q
$THETA 100 FIX ;prior on V3
$OMEGA BLOCK(12)
0.000019
0.000012 0.000273
0.000064 0.000023 0.222000
0.001050 0.003400 0.014900 0.942000
-0.000531 0.000103 -0.01280 -0.029203 0.170000
-0.005452 -0.000972 -0.291002 -0.587002 1.150000 23.100000

$OMEGA 0.1 FIX ;prior on IIV_ALAG
$OMEGA 0.1 FIX ;prior on IIV_KA
$OMEGA 0.1 FIX ;prior on IIV_CL
$OMEGA 0.1 FIX ;prior on IIV_V2
$OMEGA BLOCK(2)
0.1 ;prior on IIV_Q
0.01 0.1 FIX ;prior on IIV_V3
$THETA 2 FIX ;d.f. ALAG
$THETA 2 FIX ;d.f. KA
$THETA 2 FIX ;d.f. CL
$THETA 2 FIX ;d.f. V2
$THETA 2 FIX ;d.f. Q
$THETA 2 FIX ;d.f. V3

$EST METHOD=HYBRID ZERO=(1) SIGDIGITS=3 MAXEVAL=9999 PRINT=5
 NOABORT MSFO=msf001
$COV MATRIX=R PRINT=E
$TABLE ID TIME DOSE IPRED IWRES NOPRINT ONEHEADER FILE=sdtab001

Thanks and best regards
Nele
______________________________________________________________

Dr. Nele Kner
Pharmacometrics -- Modeling and Simulation

Nycomed GmbH
Byk-Gulden-Str. 2
D-78467 Konstanz, Germany

Fon: (+49) 7531 / 84 - 4759
Fax: (+49) 7531 / 84 - 94759

mailto: nele.kaessner
http://www.nycomed.com

County Court: Freiburg, Commercial Register HRB 701257
Chairman Supervisory Board: Charles Depasse
Management Board: Dr. Barthold Piening, Gilbert Rademacher, Dr. Anders
Ullman





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Received on Fri Sep 04 2009 - 05:15:05 EDT

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