Dear nonmem users,
We used the option “-2 RATE” of NONMEM (actual rate of infusion is
unknown): within the control stream:
D1=THETA(1)
Moreover, since several infusions are given to the same patients, we have
added an inter-occasion variability on D1 (see code below)*
We obtained nice fit BUT in the OUTPUT DATA: TIME values corresponding to
blood samples (and DV) are not identical to the actual TIME values of the
INPUT data !?
It seems that NONMEM program adjusts rate values, their interoccasion
variability, and sampling times to have a good fit
*How to fix TIME value corresponding to blood samples ? Indeed, we do not
know the actual infusion rate but we do know the sampling times.*
Can anyone tell me if I chose the right model or help me resolving this?
Thanks in advance,
*$PK
OCC1=0
OCC2=0
IF(DATE.EQ.1) OCC1=1
IF(DATE.EQ.2) OCC2=1
D1=THETA(1)*EXP(ETA(3)+ETA(4)*OCC1+ETA(5)*OCC2)
$THETA (0,168,);D1
$OMEGA .1 ; iiv d1
$OMEGA BLOCK(1) .01 ; iov ETA4 OCC1
$OMEGA BLOCK(1) SAME ; iov ETA5 OCC2
*Loïc FIEVET*
*Interne IPR en pharmacocinétique (1er semestre)*
*Institut Universitaire du Cancer Toulouse - Oncopole*
1 avenue Irène Joliot-Curie
31059 TOULOUSE Cedex 9
variation of time values in output data
it could be rounding issue when the precision of the TIME in the data file exceeds the precision of the TIME in the output of the table. You could increase precision of the output using format statement (see manual). Other than that, NONMEM should not change TIME variable.
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Quoted reply history
On 4/20/2015 12:12 PM, Diane-Charlotte Imbs wrote:
> Dear nonmem users,
>
> We used the option “-2 RATE” of NONMEM (actual rate of infusion is
> unknown): within the control stream:
>
> D1=THETA(1)
>
> Moreover, since several infusions are given to the same patients, we
> have added an inter-occasion variability on D1 (see code below)*
>
> We obtained nice fit BUT in the OUTPUT DATA: TIME values corresponding
> to blood samples (and DV) are not identical to the actual TIME values of
> the INPUT data !?
>
> It seems that NONMEM program adjusts rate values, their interoccasion
> variability, and sampling times to have a good fit
>
> *How to fix TIME value corresponding to blood samples ? Indeed, we do
> not know the actual infusion rate but we do know the sampling times.*
>
> **
>
> Can anyone tell me if I chose the right model or help me resolving this?
>
> Thanks in advance,
>
> *$PK
>
> OCC1=0
>
> OCC2=0
>
> IF(DATE.EQ.1) OCC1=1
>
> IF(DATE.EQ.2) OCC2=1
>
> D1=THETA(1)*EXP(ETA(3)+ETA(4)*OCC1+ETA(5)*OCC2)
>
> $THETA (0,168,);D1
>
> $OMEGA .1 ; iiv d1
>
> $OMEGA BLOCK(1) .01 ; iov ETA4 OCC1
>
> $OMEGA BLOCK(1) SAME ; iov ETA5 OCC2
>
> *Loïc FIEVET*
>
> */Interne IPR en pharmacocinétique (1^er semestre)/*
>
> *Institut Universitaire du Cancer Toulouse - Oncopole*
>
> 1 avenue Irène Joliot-Curie
>
> 31059 TOULOUSE Cedex 9
Thank you, Leonid, for your answer but you can see (below) it’s not a
rounding issue ; there are udge variations of time ?!!!
*INPUT FILE :*
ID DATE TIME DV AMT
RATE MDV EVID
3 1 0 0
2000 -2 1 1
3 1 2.6 1060
. . 0 0
3 1 170.1166667 331 .
. 0 0
3 2 170.1166667 . 2000
-2 1 1
3 2 172.1166667 1220 .
. 0 0
3 2 326.3333333 220 .
. 0 0
3 3 326.55 . 2000
-2 1 1
3 3 328.6166667 964 .
. 0 0
3 3 504.8333333 1260 .
. 0 0
*OUTPUT FILE :*
ID DATE TIME IPRED CL
D1 V1 IWRES
3 1 0 0
1.7711 113.17 35.217 0
3 1 2.6 1223 1.7711
113.17 35.217 -0.13328
3 1 170.12 567.29 1.7711
113.17 35.217 -0.41653
3 2 194.12 169.68 1.7711
112.49 35.217 -1
3 2 196.12 1114 1.7711
112.49 35.217 0.09514
3 2 350.33 1110 1.7711
112.49 35.217 -0.80181
3 3 374.55 328.36 1.7711
140.63 35.217 -1
3 3 376.62 1089.8 1.7711
140.63 35.217 -0.11542
3 3 552.83 1208.1 1.7711
140.63 35.217 0.04297
Loïc FIEVET
Interne IPR en pharmacocinétique
Institut Universitaire du Cancer Toulouse - Oncopole
1 avenue Irène Joliot-Curie
31059 TOULOUSE Cedex 9
Quoted reply history
2015-04-20 19:21 GMT+02:00 Leonid Gibiansky <[email protected]>:
> it could be rounding issue when the precision of the TIME in the data file
> exceeds the precision of the TIME in the output of the table. You could
> increase precision of the output using format statement (see manual). Other
> than that, NONMEM should not change TIME variable.
>
> Leonid
>
> --------------------------------------
> Leonid Gibiansky, Ph.D.
> President, QuantPharm LLC
> web: www.quantpharm.com
> e-mail: LGibiansky at quantpharm.com
> tel: (301) 767 5566
>
>
>
> On 4/20/2015 12:12 PM, Diane-Charlotte Imbs wrote:
>
>> Dear nonmem users,
>>
>> We used the option “-2 RATE” of NONMEM (actual rate of infusion is
>> unknown): within the control stream:
>>
>> D1=THETA(1)
>>
>> Moreover, since several infusions are given to the same patients, we
>> have added an inter-occasion variability on D1 (see code below)*
>>
>> We obtained nice fit BUT in the OUTPUT DATA: TIME values corresponding
>> to blood samples (and DV) are not identical to the actual TIME values of
>> the INPUT data !?
>>
>> It seems that NONMEM program adjusts rate values, their interoccasion
>> variability, and sampling times to have a good fit
>>
>> *How to fix TIME value corresponding to blood samples ? Indeed, we do
>> not know the actual infusion rate but we do know the sampling times.*
>>
>> **
>>
>> Can anyone tell me if I chose the right model or help me resolving this?
>>
>> Thanks in advance,
>>
>> *$PK
>>
>> OCC1=0
>>
>> OCC2=0
>>
>> IF(DATE.EQ.1) OCC1=1
>>
>> IF(DATE.EQ.2) OCC2=1
>>
>> D1=THETA(1)*EXP(ETA(3)+ETA(4)*OCC1+ETA(5)*OCC2)
>>
>> $THETA (0,168,);D1
>>
>> $OMEGA .1 ; iiv d1
>>
>> $OMEGA BLOCK(1) .01 ; iov ETA4 OCC1
>>
>> $OMEGA BLOCK(1) SAME ; iov ETA5 OCC2
>>
>>
>> *Loïc FIEVET*
>>
>> */Interne IPR en pharmacocinétique (1^er semestre)/*
>>
>> *Institut Universitaire du Cancer Toulouse - Oncopole*
>>
>> 1 avenue Irène Joliot-Curie
>>
>> 31059 TOULOUSE Cedex 9
>>
>>
Dear Diane-Charlotte,
NONMEM interprets DATE in your in-data and makes use of it. If you don’t want
that, rename DATE to something that is not recognized. Each date aboce the
first adds 24 h to your time column
Best regards,
Mats
Mats Karlsson, PhD
Professor of Pharmacometrics
Dept of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
75124 Uppsala
Phone: +46 18 4714105
Fax + 46 18 4714003
http://www.farmbio.uu.se/research/researchgroups/pharmacometrics/
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Diane-Charlotte Imbs
Sent: Tuesday, April 21, 2015 11:47 AM
To: Leonid Gibiansky
Cc: [email protected]
Subject: Re: [NMusers] variation of time values in output data
Thank you, Leonid, for your answer but you can see (below) it’s not a rounding
issue ; there are udge variations of time ?!!!
INPUT FILE :
ID DATE TIME DV AMT RATE
MDV EVID
3 1 0 0 2000 -2
1 1
3 1 2.6 1060 . .
0 0
3 1 170.1166667 331 . .
0 0
3 2 170.1166667 . 2000 -2
1 1
3 2 172.1166667 1220 . .
0 0
3 2 326.3333333 220 . .
0 0
3 3 326.55 . 2000 -2
1 1
3 3 328.6166667 964 . .
0 0
3 3 504.8333333 1260 . .
0 0
OUTPUT FILE :
ID DATE TIME IPRED CL D1
V1 IWRES
3 1 0 0 1.7711
113.17 35.217 0
3 1 2.6 1223 1.7711
113.17 35.217 -0.13328
3 1 170.12 567.29 1.7711 113.17
35.217 -0.41653
3 2 194.12 169.68 1.7711 112.49
35.217 -1
3 2 196.12 1114 1.7711 112.49
35.217 0.09514
3 2 350.33 1110 1.7711 112.49
35.217 -0.80181
3 3 374.55 328.36 1.7711 140.63
35.217 -1
3 3 376.62 1089.8 1.7711 140.63
35.217 -0.11542
3 3 552.83 1208.1 1.7711 140.63
35.217 0.04297
Loïc FIEVET
Interne IPR en pharmacocinétique
Institut Universitaire du Cancer Toulouse - Oncopole
1 avenue Irène Joliot-Curie
31059 TOULOUSE Cedex 9
2015-04-20 19:21 GMT+02:00 Leonid Gibiansky
<[email protected]<mailto:[email protected]>>:
it could be rounding issue when the precision of the TIME in the data file
exceeds the precision of the TIME in the output of the table. You could
increase precision of the output using format statement (see manual). Other
than that, NONMEM should not change TIME variable.
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: http://www.quantpharm.com
e-mail: LGibiansky at http://quantpharm.com
tel: (301) 767 5566
On 4/20/2015 12:12 PM, Diane-Charlotte Imbs wrote:
Dear nonmem users,
We used the option “-2 RATE” of NONMEM (actual rate of infusion is
unknown): within the control stream:
D1=THETA(1)
Moreover, since several infusions are given to the same patients, we
have added an inter-occasion variability on D1 (see code below)*
We obtained nice fit BUT in the OUTPUT DATA: TIME values corresponding
to blood samples (and DV) are not identical to the actual TIME values of
the INPUT data !?
It seems that NONMEM program adjusts rate values, their interoccasion
variability, and sampling times to have a good fit
*How to fix TIME value corresponding to blood samples ? Indeed, we do
not know the actual infusion rate but we do know the sampling times.*
**
Can anyone tell me if I chose the right model or help me resolving this?
Thanks in advance,
*$PK
OCC1=0
OCC2=0
IF(DATE.EQ.1) OCC1=1
IF(DATE.EQ.2) OCC2=1
D1=THETA(1)*EXP(ETA(3)+ETA(4)*OCC1+ETA(5)*OCC2)
$THETA (0,168,);D1
$OMEGA .1 ; iiv d1
$OMEGA BLOCK(1) .01 ; iov ETA4 OCC1
$OMEGA BLOCK(1) SAME ; iov ETA5 OCC2
*Loïc FIEVET*
*/Interne IPR en pharmacocinétique (1^er semestre)/*
*Institut Universitaire du Cancer Toulouse - Oncopole*
1 avenue Irène Joliot-Curie
31059 TOULOUSE Cedex 9
If you subtract (DATE-1) * 24 from TIME in the output file it will match TIME
in input file.
NONMEM reads DATE as a DATE data item, that’s why. I suspect you won’t have
this if you choose another column name for DATE (e.g. DAY). Note that this may
also have an effect on the estimation process and thus your parameter estimates
may change as well (for the better).
Best regards,
Klaas
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Diane-Charlotte Imbs
Sent: Tuesday, April 21, 2015 11:47 AM
To: Leonid Gibiansky
Cc: [email protected]
Subject: Re: [NMusers] variation of time values in output data
Thank you, Leonid, for your answer but you can see (below) it’s not a rounding
issue ; there are udge variations of time ?!!!
INPUT FILE :
ID DATE TIME DV AMT RATE
MDV EVID
3 1 0 0 2000 -2
1 1
3 1 2.6 1060 . .
0 0
3 1 170.1166667 331 . .
0 0
3 2 170.1166667 . 2000 -2
1 1
3 2 172.1166667 1220 . .
0 0
3 2 326.3333333 220 . .
0 0
3 3 326.55 . 2000 -2
1 1
3 3 328.6166667 964 . .
0 0
3 3 504.8333333 1260 . .
0 0
OUTPUT FILE :
ID DATE TIME IPRED CL D1
V1 IWRES
3 1 0 0 1.7711
113.17 35.217 0
3 1 2.6 1223 1.7711
113.17 35.217 -0.13328
3 1 170.12 567.29 1.7711 113.17
35.217 -0.41653
3 2 194.12 169.68 1.7711 112.49
35.217 -1
3 2 196.12 1114 1.7711 112.49
35.217 0.09514
3 2 350.33 1110 1.7711 112.49
35.217 -0.80181
3 3 374.55 328.36 1.7711 140.63
35.217 -1
3 3 376.62 1089.8 1.7711 140.63
35.217 -0.11542
3 3 552.83 1208.1 1.7711 140.63
35.217 0.04297
Loïc FIEVET
Interne IPR en pharmacocinétique
Institut Universitaire du Cancer Toulouse - Oncopole
1 avenue Irène Joliot-Curie
31059 TOULOUSE Cedex 9
2015-04-20 19:21 GMT+02:00 Leonid Gibiansky
<[email protected]<mailto:[email protected]>>:
it could be rounding issue when the precision of the TIME in the data file
exceeds the precision of the TIME in the output of the table. You could
increase precision of the output using format statement (see manual). Other
than that, NONMEM should not change TIME variable.
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: http://www.quantpharm.com
e-mail: LGibiansky at http://quantpharm.com
tel: (301) 767 5566
On 4/20/2015 12:12 PM, Diane-Charlotte Imbs wrote:
Dear nonmem users,
We used the option “-2 RATE” of NONMEM (actual rate of infusion is
unknown): within the control stream:
D1=THETA(1)
Moreover, since several infusions are given to the same patients, we
have added an inter-occasion variability on D1 (see code below)*
We obtained nice fit BUT in the OUTPUT DATA: TIME values corresponding
to blood samples (and DV) are not identical to the actual TIME values of
the INPUT data !?
It seems that NONMEM program adjusts rate values, their interoccasion
variability, and sampling times to have a good fit
*How to fix TIME value corresponding to blood samples ? Indeed, we do
not know the actual infusion rate but we do know the sampling times.*
**
Can anyone tell me if I chose the right model or help me resolving this?
Thanks in advance,
*$PK
OCC1=0
OCC2=0
IF(DATE.EQ.1) OCC1=1
IF(DATE.EQ.2) OCC2=1
D1=THETA(1)*EXP(ETA(3)+ETA(4)*OCC1+ETA(5)*OCC2)
$THETA (0,168,);D1
$OMEGA .1 ; iiv d1
$OMEGA BLOCK(1) .01 ; iov ETA4 OCC1
$OMEGA BLOCK(1) SAME ; iov ETA5 OCC2
*Loïc FIEVET*
*/Interne IPR en pharmacocinétique (1^er semestre)/*
*Institut Universitaire du Cancer Toulouse - Oncopole*
1 avenue Irène Joliot-Curie
31059 TOULOUSE Cedex 9
I think the problem is the DATE column. If this column is called DATE also in
$INPUT it will be interpreted as a date and NONMEM will adjust your time
according to that date, adding 24 hours.
Even though you put =DROP on this column NM will recognise DATE. Call is
something else unless you want to have it on different times.
Kind regards,
Mia
_________________________________
Maria Kjellsson, PhD
Associate Professor in Pharmacometrics
Pharmacometrics research group
Dep of Pharmaceutical Biosciences
Uppsala University
Box 591
SE-751 24 Uppsala, Sweden
Phone: +46 18 471 4009
http://www.farmbio.uu.se/research/researchgroups/pharmacometrics
Quoted reply history
On 21 Apr 2015, at 11:46, Diane-Charlotte Imbs
<[email protected]<mailto:[email protected]>> wrote:
Thank you, Leonid, for your answer but you can see (below) it’s not a rounding
issue ; there are udge variations of time ?!!!
INPUT FILE :
ID DATE TIME DV AMT RATE
MDV EVID
3 1 0 0 2000 -2
1 1
3 1 2.6 1060 . .
0 0
3 1 170.1166667 331 . .
0 0
3 2 170.1166667 . 2000 -2
1 1
3 2 172.1166667 1220 . .
0 0
3 2 326.3333333 220 . .
0 0
3 3 326.55 . 2000 -2
1 1
3 3 328.6166667 964 . .
0 0
3 3 504.8333333 1260 . .
0 0
OUTPUT FILE :
ID DATE TIME IPRED CL D1
V1 IWRES
3 1 0 0 1.7711
113.17 35.217 0
3 1 2.6 1223 1.7711
113.17 35.217 -0.13328
3 1 170.12 567.29 1.7711 113.17
35.217 -0.41653
3 2 194.12 169.68 1.7711 112.49
35.217 -1
3 2 196.12 1114 1.7711 112.49
35.217 0.09514
3 2 350.33 1110 1.7711 112.49
35.217 -0.80181
3 3 374.55 328.36 1.7711 140.63
35.217 -1
3 3 376.62 1089.8 1.7711 140.63
35.217 -0.11542
3 3 552.83 1208.1 1.7711 140.63
35.217 0.04297
Loïc FIEVET
Interne IPR en pharmacocinétique
Institut Universitaire du Cancer Toulouse - Oncopole
1 avenue Irène Joliot-Curie
31059 TOULOUSE Cedex 9
2015-04-20 19:21 GMT+02:00 Leonid Gibiansky
<[email protected]<mailto:[email protected]>>:
it could be rounding issue when the precision of the TIME in the data file
exceeds the precision of the TIME in the output of the table. You could
increase precision of the output using format statement (see manual). Other
than that, NONMEM should not change TIME variable.
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: http://www.quantpharm.com/
e-mail: LGibiansky at http://quantpharm.com/
tel: (301) 767 5566
On 4/20/2015 12:12 PM, Diane-Charlotte Imbs wrote:
Dear nonmem users,
We used the option “-2 RATE” of NONMEM (actual rate of infusion is
unknown): within the control stream:
D1=THETA(1)
Moreover, since several infusions are given to the same patients, we
have added an inter-occasion variability on D1 (see code below)*
We obtained nice fit BUT in the OUTPUT DATA: TIME values corresponding
to blood samples (and DV) are not identical to the actual TIME values of
the INPUT data !?
It seems that NONMEM program adjusts rate values, their interoccasion
variability, and sampling times to have a good fit
*How to fix TIME value corresponding to blood samples ? Indeed, we do
not know the actual infusion rate but we do know the sampling times.*
**
Can anyone tell me if I chose the right model or help me resolving this?
Thanks in advance,
*$PK
OCC1=0
OCC2=0
IF(DATE.EQ.1) OCC1=1
IF(DATE.EQ.2) OCC2=1
D1=THETA(1)*EXP(ETA(3)+ETA(4)*OCC1+ETA(5)*OCC2)
$THETA (0,168,);D1
$OMEGA .1 ; iiv d1
$OMEGA BLOCK(1) .01 ; iov ETA4 OCC1
$OMEGA BLOCK(1) SAME ; iov ETA5 OCC2
*Loïc FIEVET*
*/Interne IPR en pharmacocinétique (1^er semestre)/*
*Institut Universitaire du Cancer Toulouse - Oncopole*
1 avenue Irène Joliot-Curie
31059 TOULOUSE Cedex 9