Re: Time-varing covariate

On Wed, Aug 28, 2013, at 12:53 AM, Nick Holford wrote: 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 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 <[1][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:[2]+64(9)923-6730 mobile:NZ [3]+64(21)46 23 53 FR [4]+33(7)85 36 84 99 email: [5][email protected] [6] http://holford.fmhs.auckland.ac.nz/ Holford NHG. Disease progression and neuroscience. Journal of Pharmacokinetics and Pharmacodynamics. 2013;40:369-76 [7] 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: [8] http://onlinelibrary.wiley.com/doi/10.1002/jps.23574/abstract Holford N. A time to event tutorial for pharmacometricians. CPT:PSP. 2013;2: [9] 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: [10] http://onlinelibrary.wiley.com/doi/10.1111/bcp.12170/abstract -- Alison Boeckmann [11][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: [12][email protected] [13] http://holford.fmhs.auckland.ac.nz/ Holford NHG. Disease progression and neuroscience. Journal of Pharmacokinetics a nd Pharmacodynamics. 2013;40:369-76 [14] 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: [15] http://onlinelibrary.wiley.com/doi/10.1002/jps.23574/ab stract Holford N. A time to event tutorial for pharmacometricians. CPT:PSP. 2013;2: [16 ] 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: [17] http://onlinelibrary.wiley.com/doi/1 0.1111/bcp.12170/abstract References 1. mailto:[email protected] 2. tel:%2B64%289%29923-6730 3. tel:%2B64%2821%2946%2023%2053 4. tel:%2B33%287%2985%2036%2084%2099 5. mailto:[email protected] 6. http://holford.fmhs.auckland.ac.nz/ 7. http://link.springer.com/article/10.1007/s10928-013-9316-2 8. http://onlinelibrary.wiley.com/doi/10.1002/jps.23574/abstract 9. http://www.nature.com/psp/journal/v2/n5/full/psp201318a.html 10. http://onlinelibrary.wiley.com/doi/10.1111/bcp.12170/abstract 11. mailto:[email protected] 12. mailto:[email protected] 13. http://holford.fmhs.auckland.ac.nz/ 14. http://link.springer.com/article/10.1007/s10928-013-9316-2 15. http://onlinelibrary.wiley.com/doi/10.1002/jps.23574/abstract 16. http://www.nature.com/psp/journal/v2/n5/full/psp201318a.html 17. http://onlinelibrary.wiley.com/doi/10.1111/bcp.12170/abstract -- Alison Boeckmann [email protected]