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Re: Time-varing covariate

From: Alison Boeckmann <alisonboeckmann>
Date: Tue, 27 Aug 2013 13:45:44 -0700

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]n.holford

  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]n.holford
  [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

References

1. mailto:n.holford
2. tel:%2B64%289%29923-6730
3. tel:%2B64%2821%2946%2023%2053
4. tel:%2B33%287%2985%2036%2084%2099
5. mailto:n.holford
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
--
  Alison Boeckmann
  alisonboeckmann


Received on Tue Aug 27 2013 - 16:45:44 EDT

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