Re: NONMEM Tips #21 - What Bill didn't tell you
From: "Nick Holford"
Subject: Re: [NMusers] NONMEM Tips #21 - What Bill didn't tell you
Date: Fri, May 27, 2005 8:27 am
Thanks to those of you sent me this NONMEM Tip.
Its a bit of a mystery how NM-TRAN/NONMEM interpret the data items when CONT=1. I am
unclear what is done with positions that correspond to data items with special
meaning in the record with CONT=0.
It seems that every record (no matter with CONT=0 or CONT=1) for the same individual
must have the same ID. The following data fragment makes NONMEM think there are 24
subjects and the run finishes with a very different objective function.
C Data Desc: using more than one line per record
C JUNK JNK2 AGE STDY FORM WT CONT
C ID TIME AMT DV SEX LAB CONT
-1 -1 22 802 0 79.6 1
1 0 4.02 . 1 3 0
-1 -1 22 802 0 . 1
1 0 . 0.74 1 3 0
-1 -1 22 802 0 . 1
1 0.25 . 2.84 1 3 0
-1 -1 22 802 0 . 1
1 0.57 . 6.57 1 3 0
-1 -1 22 802 0 . 1
1 1.12 . 10.5 1 3 0
-1 -1 22 802 0 . 1
1 2.02 . 9.66 1 3 0
-1 -1 22 802 0 . 1
1 3.82 . 8.58 1 3 0
-1 -1 22 802 0 . 1
1 5.1 . 8.36 1 3 0
-1 -1 22 802 0 . 1
1 7.03 . 7.47 1 3 0
-1 -1 22 802 0 . 1
1 9.05 . 6.89 1 3 0
-1 -1 22 802 0 . 1
1 12.12 . 5.94 1 3 0
-1 -1 22 802 0 . 1
1 24.37 . 3.28 1 3 0
On the other hand it seems that the TIME data item when CONT=1 is ignored because
NONMEM will complain if you use a negative TIME with $PK. Based on rather limited
testing it seems the only required thing is to have ID on every record for a given
subject. Some data items on records with CONT=1 are looked at by NM-TRAN and give
spurious warnings (e.g. DV and MDV; see below) but not by NONMEM.
Using the control stream and data fragment provided in Tip #21 I get the following
output. It seems that NM-TRAN is trying to interpret DV and MDV when it reads a
record with CONT=1. These warnings can be switched off with $WARN DATA=NONE if they
annoy you.
WARNINGS AND ERRORS (IF ANY) FOR PROBLEM 1
(WARNING 2) NM-TRAN INFERS THAT THE DATA ARE POPULATION.
(DATA WARNING 5) RECORD 1, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 3, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 5, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 7, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 9, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 11, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 13, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 15, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 17, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 19, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 21, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 23, DATA ITEM 5: 802
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
df /fltconsistency /optimize:4 /fast /Fecont FSUBS.for @link.txt
NONMEM cont...
MONITORING OF SEARCH:
0ITERATION NO.: 0 OBJECTIVE VALUE: 18.101 NO. OF FUNC. EVALS.: 6
CUMULATIVE NO. OF FUNC. EVALS.: 6
PARAMETER: 0.1000E+00 0.1000E+00 0.1000E+00 0.1000E+00 0.1000E+00 0.1000E
+00 0.1000E+00 0.1000E+00 0.1000E+00 0.1000E+00
GRADIENT: -0.1334E+03 -0.4117E+03 0.1506E+04 0.6870E+01 0.3766E+01 -0.1760E
+02 0.4215E+02 -0.7837E+02 -0.1521E+03 -0.1788E+02
0ITERATION NO.: 47 OBJECTIVE VALUE: -3.897 NO. OF FUNC. EVALS.:11
CUMULATIVE NO. OF FUNC. EVALS.: 455
PARAMETER: 0.1302E+00 -0.6904E-01 -0.6362E-01 0.2537E+00 -0.5180E+00 -0.8572E
-01 -0.3027E-02 -0.2925E-02 0.5712E-04 0.6498E-01
GRADIENT: -0.1154E+02 0.1046E+03 -0.2030E+03 0.4912E+01 0.2036E+01 -0.5541E
+01 -0.7725E+01 0.1166E+01 0.3292E+01 0.1007E+01
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/