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RE: Time-varing covariate

From: Mats Karlsson <mats.karlsson>
Date: Wed, 28 Aug 2013 09:00:51 +0200

Dear Alison,


It may be clearer. It certainly would capture most covariate changes but on
the other hand you may need to used EVID=2 even when the physiological
variable change is at an observation/dose event (if you want to have the
covariate values feed forward rather than backwards). Also, you may not need
to have to use EVID=2 to make the covariate change at other times than event
times (as my example code tried to illustrate).


Best regards,


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



From: owner-nmusers
Behalf Of Alison Boeckmann
Sent: 27 August 2013 22:46
To: siwei Dai; ajbf
Cc: nmusers
Subject: Re: [NMusers] Time-varing covariate


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?




Best regards,




On Fri, Aug 23, 2013 at 1:10 PM, Nick Holford <n.holford


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.


; 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,


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,

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
email: n.holford

Holford NHG. Disease progression and neuroscience. Journal of
Pharmacokinetics and Pharmacodynamics. 2013;40:369-76
Holford N, Heo Y-A, Anderson B. A pharmacokinetic standard for babies and
adults. J Pharm Sci. 2013:
Holford N. A time to event tutorial for pharmacometricians. CPT:PSP. 2013;2:
Holford NHG. Clinical pharmacology = disease progression + drug action.
British Journal of Clinical Pharmacology. 2013:




Alison Boeckmann


Received on Wed Aug 28 2013 - 03:00:51 EDT

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