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Re: [NMusers] Using evid 0 before dosing

From: Dennis Fisher <fisher_at_plessthan.com>
Date: Wed, 6 Nov 2019 08:44:36 -0800

Mark

I disagree (more than a little). If a sample is reported as BQL and the =
expected value is 0 (i.e., pre-dose, not endogenous), what information =
is there about assay precision. If the error model is additive (or =
additive + proportional), the sample will contribute zero to the =
objective function. If the error model is proportional, NONMEM will =
report an error (0/0). I agree that pre-dose samples > LOQ provide =
IMPORTANT information about assay precision.

Were you evacuated during the fires?

Dennis

Dennis Fisher MD
P < (The "P Less Than" Company)
Phone / Fax: 1-866-PLessThan (1-866-753-7784)
www.PLessThan.com <http://www.plessthan.com/>




> On Nov 6, 2019, at 8:40 AM, Mark Sale <msale_at_nuventra.com> wrote:
>
> Dennis,
> I may have to disagree, a little. There is information, a little, in a =
pre dose BQL, about assay precision. I think you might agree that is a =
pre dose sample is NOT BQL (which happens), tells you (and NONMEM) =
something about the assay. Converse, even a BQL predose sample has a =
small amount of information.
> That not withstanding, we also remove and pre-dose BQLs from the data =
set.
>
>
> Mark Sale M.D.
> Senior Vice President, Pharmacometrics
> Nuventra Inc.
> 2525 Meridian Parkway, Suite 200
> Durham, NC 27713
> Phone (919)-973-0383
> msale_at_nuventra.com <x-msg://138/msale_at_kinetigen.com>
>
>
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> From: owner-nmusers_at_globomaxnm.com =
<mailto:owner-nmusers_at_globomaxnm.com> <owner-nmusers_at_globomaxnm.com =
<mailto:owner-nmusers_at_globomaxnm.com>> on behalf of Dennis Fisher =
<fisher_at_plessthan.com <mailto:fisher_at_plessthan.com>>
> Sent: Wednesday, November 6, 2019 7:23 AM
> To: nmusers_at_globomaxnm.com <mailto:nmusers_at_globomaxnm.com> =
<nmusers_at_globomaxnm.com <mailto:nmusers_at_globomaxnm.com>>; Bill Denney =
<wdenney_at_humanpredictions.com <mailto:wdenney_at_humanpredictions.com>>
> Cc: Carlos ST <carlos.serra91_at_gmail.com =
<mailto:carlos.serra91_at_gmail.com>>; Steven Shafer =
<steven.shafer_at_stanford.edu <mailto:steven.shafer_at_stanford.edu>>
> Subject: Re: [NMusers] Using evid 0 before dosing
>
> WARNING: This email originated from outside of the company. Do not =
click links or open attachments unless you recognize the sender and are =
expecting the message.
> Bill
>
> I think that the issue is more complicated than you acknowledge.
>
> Assuming that the drug is not an endogenous substance, the pre-dose =
concentration is likely to be BQL. However, there are two kinds of BQL =
values:
> 1. Samples that are truly zero because they were obtained pre-dose
> 2. Samples that are > 0 but < LOQ.
> Yet both are reported as BQL.
>
> From my perspective, a BQL value pre-dose provides no information to =
NONMEM. Therefore, one should apply EVID=2 to that sample. This =
allows a prediction at that timepoint but the sample does not influence =
the analysis.
>
> Dennis
>
> Dennis Fisher MD
> P < (The "P Less Than" Company)
> Phone / Fax: 1-866-PLessThan (1-866-753-7784)
> www.PLessThan.com <http://www.plessthan.com/>
>
>
>
>
>> On Nov 6, 2019, at 7:12 AM, Bill Denney <wdenney_at_humanpredictions.com =
<mailto: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 =
<mailto:owner-nmusers_at_globomaxnm.com> <owner-nmusers_at_globomaxnm.com =
<mailto:owner-nmusers_at_globomaxnm.com>> On Behalf
>> Of Carlos ST
>> Sent: Wednesday, November 6, 2019 10:03 AM
>> To: nmusers_at_globomaxnm.com <mailto: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,



Received on Wed Nov 06 2019 - 11:44:36 EST

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