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Re: [NMusers] Using evid 0 before dosing

From: Mark Sale <msale_at_nuventra.com>
Date: Wed, 6 Nov 2019 17:03:10 +0000

If >LLOQ has information, then !>LLOQ MUST also have information.
and Yes, we evacuated for 6 days, back home now.


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<msale_at_kinetigen.com>


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________________________________
From: Dennis Fisher <fisher_at_plessthan.com>
Sent: Wednesday, November 6, 2019 8:44 AM
To: Mark Sale <msale_at_nuventra.com>
Cc: nmusers_at_globomaxnm.com <nmusers_at_globomaxnm.com>
Subject: Re: [NMusers] Using evid 0 before dosing


WARNING: This email originated from outside of the company. Do not click li=
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he message.

Mark

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

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<mailto:msale_at_nuve=
ntra.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 inform=
ation.
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





CONFIDENTIALITY NOTICE The information in this transmittal (including attac=
hments, if any) may be privileged and confidential and is intended only for=
 the recipient(s) listed above. Any review, use, disclosure, distribution o=
r copying of this transmittal, in any form, is prohibited except by or on b=
ehalf of the intended recipient(s). If you have received this transmittal i=
n error, please notify me immediately by reply email and destroy all copies=
 of the transmittal.

________________________________
From: owner-nmusers_at_globomaxnm.com<mailto:owner-nmusers_at_globomaxnm.com> <ow=
ner-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_globomax=
nm.com<mailto:nmusers_at_globomaxnm.com>>; Bill Denney <wdenney_at_humanpredictio=
ns.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 li=
nks or open attachments unless you recognize the sender and are expecting t=
he 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 concent=
ration 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 pred=
iction 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<mailt=
o: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 i=
n
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> <ow=
ner-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 - 12:03:10 EST

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