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Re: [NMusers] Using evid 0 before dosing

From: Paolo Denti <paolo.denti_at_uct.ac.za>
Date: Wed, 6 Nov 2019 16:02:12 +0000

Hi Carlos,
Adding to what the others suggested, please note that, if that EVID=0
record is the very first record for that patient, NONMEM will predict
all compartments to be empty (all amounts = 0) at that time (unless you
initialise as discussed below).

If indeed there were no doses before that sample and therefore the
pre-dose sample is expected to contain no drug (it will come back as
undetectable, or BLQ), then I think you should just use it as a check,
but I would NOT fit that sample in the model, as it does not add much,
and it is possibly a bit tricky to implement in NONMEM due to the 0
predictions.

If, on the other hand, there were other doses before and the
concentration in that sample could be (or maybe it's even expected to
be) detectable, then you should fit that data point in the model.
For that to happen, though, NONMEM needs to be able to predict something
other than 0, in there, so you need to
1. either include in the dataset all the records for the previous doses
(preferred if the dosing history is available)
2. or initialise the system to some value.

For some ideas on approached for initialisation, you can have a look at
the paper below.
Dansirikul, C., Silber, H. E., & Karlsson, M. O. (2008). Approaches to
handling pharmacodynamic baseline responses. Journal of Pharmacokinetics
and Pharmacodynamics, 35(3), 269–283.
https://doi.org/10.1007/s10928-008-9088-2

Good luck.
Paolo

On 2019/11/06 17:48, Carlos ST wrote:
> Hi NMUsers community for you excellent suggestions. I will work through it.
> Thanks,
>
> Carlos
>
>
>
> On Wed, 6 Nov 2019 at 15:12, Bill Denney <wdenney_at_humanpredictions.com> wrote:
>> Hi Carlos,
>>
>> It is commonly used. For most datasets, there will be at least one
>> observation that occurs before dosing to estimate the baseline value, and in
>> almost every scenario, the modeling dataset should mirror the real world
>> actions. So, there is no issue with it, and usually you will have an EVID=0
>> before the first dose.
>>
>> Thanks,
>>
>> Bill
>>
>> -----Original Message-----
>> From: owner-nmusers_at_globomaxnm.com <owner-nmusers_at_globomaxnm.com> On Behalf
>> Of Carlos ST
>> Sent: Wednesday, November 6, 2019 10:03 AM
>> To: nmusers_at_globomaxnm.com
>> Subject: [NMusers] Using evid 0 before dosing
>>
>> Dear NMUsers,
>>
>> I would like advice in the best practice to use evid 0 before dosing, which
>> is to say an observation just before a dosing (*to estimate the value in
>> that compartment just before dosing event).
>>
>> Thank you,
>>
>> Carlos,

--
------------------------------------------------
Paolo Denti, PhD
A/Prof of Pharmacometrics
Division of Clinical Pharmacology
Department of Medicine
University of Cape Town

K45 Old Main Building
Groote Schuur Hospital
Observatory, Cape Town
7925 South Africa
phone: +27 21 404 7719
fax: +27 021 650 5410
email: paolo.denti_at_uct.ac.za
------------------------------------------------

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Received on Wed Nov 06 2019 - 11:02:12 EST

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