Dear SoJeong Yi,
Hyeong-Seok Lim is right, and indeed that ETA in your model is probably accounting for both BOV and BSV.
On the other hand, if your best OFV is obtained with BOV alone (as opposed to BSV alone or both BOV+BSV), this is telling you that the BOV differences are more important than the BSV differences.
In my experience, this is very common for absorption, whose large variability is often driven by accidental factors (food intake, pH in the stomach, stomach emptying time, co-medications, moon phase :) ), rather than real differences between the patients.
I would say that in this case modellers simply report in the paper that the OMEGA was BOV, without any need for further explanation.
I hope this reassures you.
On 2015/09/04 04:49, Hyeong-Seok Lim wrote:
Dear SoJeong Yi,
Sometime we cannot estimate the variances for IIV and IOV separately, although we have multiple dosing data within each subject.
At that time, the alternative could be to combine the IIV and IOV to a single random effect parameter, which is the way you have done.
In this case, the random effect parameter can be described as “random effect parameter reflecting both IIV and IOV”, and so on.
Hyeong-Seok Lim MD PhD
Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan
88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea
Email: <mailto:mdlhs_at_amc.seoul.kr> mdlhs_at_amc.seoul.kr<mailto:mdlhs_at_amc.seoul.kr>, mdhslim_at_gmail.com<mailto:mdhslim_at_gmail.com>
From: owner-nmusers_at_globomaxnm.com<mailto:owner-nmusers_at_globomaxnm.com> [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of 이소정
Sent: Friday, September 4, 2015 11:13 AM
Subject: [NMusers] Describing Omega that includes both BSV and IOV
Currently I’m summarizing the NONMEM estimates of population PK for writing a manuscript.
However, I wonder how to describe the omega which includes both between-subject variability and inter-occasional variability.
The code of ‘variability’ is followed below,
IF(OCC.EQ.1) IOV = ETA(8)
IF(OCC.EQ.2) IOV = ETA(9)
IF(OCC.EQ.3) IOV = ETA(10)
KA = THETA(9) * EXP(IOV) (--> In final model, PK parameter was estimated like this)
; KA = THETA(9) * EXP(ETA(4)+IOV) (--> When I used this code, there were some problems (boundary error, large RSE (>80%), very small estimate of BSV and so on) )
; KA = THETA(9) * EXP(ETA(4)) (--> when I used BSV only, the OFV is quite higher than upper two cases, so I thought that IOV should be considered. )
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) 0.3
In this case, the individual eta was re-calculated in one subject according to occasion, isn’t it?
Then, how should I describe this ‘variability’ and estimate of omega in a manuscript?
(i.e., between subject variability containing inter-occasional variability? Or any other appropriate term?)
I will appreciate if someone give any advice. Thanks in advance.
SoJeong Yi, Ph.D
Department of Clinical Pharmacology and Therapeutics,
Seoul National University College of Medicine and Hospital
101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea
E-mail: <mailto:sjyi_at_snu.ac.kr> sjyi_at_snu.ac.kr<mailto:sjyi_at_snu.ac.kr>
Paolo Denti, PhD
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 21 448 1989
UNIVERSITY OF CAPE TOWN
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Received on Fri Sep 04 2015 - 03:35:40 EDT