Re: flexible infusion rate model
Tomi,
In order to help you it would be useful to have more details of your problem.
It is simple to include different infusion rates for each patient by specifying the AMT and RATE in the data file.
If you really observed that the infusion rate changed ("I observed inconsistent infusion rates (especially at the end of infusion)"
then you should code the changed RATEs with the start TIME and AMT infused.
If you mean that you know that the clinical staff played around with the infusion without really keeping any good records then it is more difficult to describe what happened. In this case you can try coding RATE with -2 in the data set and then specify the duration in $PK as D1 and add a random effect e.g.
D1=DUR*EXP(ETA(x))
where DUR is the nominal infusion duration (a data item in the data set) for that patient and ETA(x) is a random effect describing the inability of the clinical staff to do their job.
What do you mean by 'flexible infusion rates' in this context? If you give us details of your code and a sample of the data then it might be possible to help you.
Nick
Quoted reply history
On 19/08/2011 8:57 p.m., tomi hendrayana wrote:
> Dear all,
>
> Here comes a beginner modeler, who wants to share the problem with experts in the Group and looking for good solutions ;-) I try to model Pop-PK anticancer drug which was delivered by continuous venous infusion with several types of duration time such as 24 hours, 46 hours, 96 hours or 120 hours. Data came from four different studies; some patients were observed on more than 1 cycle; and sampling varied from 1 point/patient to 20 points/patient. Since I observed inconsistent infusion rates (especially at the end of infusion), which might be a potential factor for variability in PK parameter, then i try to include flexible infusion rates into the model. I made a control code but unfortunately NONMEM stopped running and had an error message:
>
> #METH: First Order Conditional Estimation with Interaction
> MONITORING OF SEARCH:
> 0PRED EXIT CODE = 1
>
> 0INDIVIDUAL NO. 1 ID= 1.00000000000000E+00 (WITHIN-INDIVIDUAL) DATA REC NO. 3
>
> THETA=
>
> 1.00E-01 1.00E-01 1.00E-01 1.00E-01 1.00E-01 1.00E-01 1.00E-01 1.00E-01 2.72E+02 3.84E+01
>
> 4.21E-01 2.52E-02
> OCCURS DURING SEARCHFOR ETA AT INITIAL VALUE, ETA=0
> PK PARAMETER FOR RATE IS NON-POSITIVE
> 0PROGRAM TERMINATED BY OBJ
> MESSAGE ISSUED FROM ESTIMATION STEP
> AT INITIAL OBJ. FUNCTION EVALUATION
> Elapsed estimation time in seconds: 0.28
> #TERM:
> #TERE:
> 1THERE ARE ERROR MESSAGES IN FILE PRDERR
>
> Hereby i sent you a part of structure data set and my control stream (see attachment). Could anyone point it out for me what could be a problem and how to handle this? Thanks in advance.
>
> yours,
> -Tomi
> PhD Student
> Uni Bonn
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology& Clinical Pharmacology
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
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email: [email protected]
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford