Re: Time-varing covariate
Alison,
I think the problem with the on-line help arose because a relatively inexperienced nmuser was searching through the help to find some clues on what to do. The use of the "physiological variable changes" expression to describe an EVID=2 event seems to have been interpreted as something special within NONMEM that knew about physiological changes. Of course, this was a misunderstanding.
To avoid the misunderstanding I suggest you make it clearer that the change in a physiological variable is just an example of a covariate change at a non-dose and non-observation event time e.g.
"Examples of other-type events are: A compartment is turned on or off (CMT specifies which compartment is to be turned on or off); a prediction is obtained at a specified time so that it may be displayed in a table or scatterplot ; some event occurs at a different time than any observation or dose event e.g. a covariate such as weight changes, an intervention such as hemodialysis is started or stopped."
Adding more specific examples of the use of EVID=2 would perhaps be useful. Does anyone have any other examples?
I also suggest removing reference to PCMT "(PCMT specifies the compartment from which the prediction is obtained)" because it is not directly relevant to EVID=2. An inexperienced user might interpret the remark about PCMT to imply that PCMT is required for use with EVID=2. In my own experience I have never found the need to use PCMT. I usually do not rely on the default compartment with complex models but use the compartment explicitly in $ERROR to define the prediction I want to output.
Best wishes,
Nick
Quoted reply history
On 27/08/2013 10:45 p.m., Alison Boeckmann wrote:
> There have been a number of interesting comments.
>
> The original issue has to do with the way this is described in on-line help for EVID.
>
> Would it be more clear if this said:
>
> > a physiological variable changes (and this is at a different time than any observation or dose event).
>
> Or can someone suggest a better wording that would not add to the confusion?
>
> On Fri, Aug 23, 2013, at 10:51 AM, siwei Dai wrote:
>
> > Hi, Nick:
> > Thank you for the response.
> >
> > I meant to say EVID = 2 but not '4', my mistake. In the user guide, it says:
> >
> > 2 Other-type event. The DV data item is ignored. Dose-related
> > data items must be zero. Examples of other-type events are: A
> > compartment is turned on or off (CMT specifies which compartment
> > is to be turned on or off); a prediction is obtained at a speci-
> > fied time so that it may be displayed in a table or scatterplot
> > (PCMT specifies the compartment from which the prediction is
> > obtained); a physiological variable changes.
> >
> > I am asking the question because I thought that usually the covariates stay the same, but I want to add a covariate that changes during the day, so every observation line will have a different covariate value. If I understand your email correctly, I don't need to do anything special to treat this type covariates then?
> >
> > Thanks!
> > Best regards,
> > Siwei
> >
> > On Fri, Aug 23, 2013 at 1:10 PM, Nick Holford < [email protected] < mailto: [email protected] >> wrote:
> >
> > Siwei,
> >
> > I don't know why you think this complicated. Suppose you have age
> > (AGE) as a covariate. This must of course be a time varying
> > covariate if it is intended to be the current age. And you might
> > have weight (WT) or creatinine clearance (CLCR) as covariates
> > which typically change with time. So just code the $INPUT data
> > items and use them as you wish e.g.
> >
> > $INPUT ID TIME AGE WT CLCR etc
> > ...
> >
> > $PK
> > ; CL=(CLnon-renal*f(age) + CLrenal*f(renal_function)) * allometric WT
> > CL=(THETA(1)*EXP(THETA(2)*(AGE-40)) +
> > THETA(3)*CLCR/100)*(WT/70)**0.75
> >
> > EVID=4 has nothing to do with using time varying covariates.
> >
> > Perhaps you could explain more clearly what your problem is and
> > why you think it is complicated to use time varying covariates?
> >
> > Best wishes,
> >
> > Nick
> >
> > On 23/08/2013 6:00 p.m., siwei Dai wrote:
> >
> > Hi, Dear NMusers:
> > I want to add a time-varing covariate in my model. For
> > example, blood pressure or blood flow as covariates. But I am
> > not sure how to do it. I see some earlier threads to discuss
> > it but they all use complicated methods.
> > I am wondering if there are any new way to do it in NM 7.2?
> > I see in the user guide that EVID=4 can indicate
> > physiological change. Is this what I should use?
> > Thank you very much for any suggestions.
> > Best regards,
> > Siwei
> >
> > --
> > Nick Holford, Professor Clinical Pharmacology
> > Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A
> > University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New
> > Zealand
> > office:+64(9)923-6730 <tel:%2B64%289%29923-6730> mobile:NZ
> > +64(21)46 23 53 <tel:%2B64%2821%2946%2023%2053> FR +33(7)85 36 84
> > 99 <tel:%2B33%287%2985%2036%2084%2099>
> > email: [email protected] <mailto:[email protected]>
> > http://holford.fmhs.auckland.ac.nz/
> >
> > Holford NHG. Disease progression and neuroscience. Journal of
> > Pharmacokinetics and Pharmacodynamics. 2013;40:369-76
> > http://link.springer.com/article/10.1007/s10928-013-9316-2
> > Holford N, Heo Y-A, Anderson B. A pharmacokinetic standard for
> > babies and adults. J Pharm Sci. 2013:
> > http://onlinelibrary.wiley.com/doi/10.1002/jps.23574/abstract
> > Holford N. A time to event tutorial for pharmacometricians.
> > CPT:PSP. 2013;2:
> > http://www.nature.com/psp/journal/v2/n5/full/psp201318a.html
> > Holford NHG. Clinical pharmacology = disease progression + drug
> > action. British Journal of Clinical Pharmacology. 2013:
> > http://onlinelibrary.wiley.com/doi/10.1111/bcp.12170/abstract
>
> --
> Alison Boeckmann
> [email protected] <mailto:[email protected]>
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
office:+64(9)923-6730 mobile:NZ +64(21)46 23 53 FR +33(7)85 36 84 99
email: [email protected]
http://holford.fmhs.auckland.ac.nz/
Holford NHG. Disease progression and neuroscience. Journal of Pharmacokinetics
and Pharmacodynamics. 2013;40:369-76
http://link.springer.com/article/10.1007/s10928-013-9316-2
Holford N, Heo Y-A, Anderson B. A pharmacokinetic standard for babies and
adults. J Pharm Sci. 2013:
http://onlinelibrary.wiley.com/doi/10.1002/jps.23574/abstract
Holford N. A time to event tutorial for pharmacometricians. CPT:PSP. 2013;2:
http://www.nature.com/psp/journal/v2/n5/full/psp201318a.html
Holford NHG. Clinical pharmacology = disease progression + drug action. British
Journal of Clinical Pharmacology. 2013:
http://onlinelibrary.wiley.com/doi/10.1111/bcp.12170/abstract