RE: Rational of using IOV
Hi Thierry,
Actually, devising a TDM program is precisely when you should be evaluating
whether you have substantial IOV. If IOV is considerably greater than IIV
then there is little benefit in a TDM program as you point out since a
concentration from one occasion may not contain much information about the
next occasion. In this setting a TDM program would be "chasing noise".
However, simply fitting a model that does not partition out IOV doesn't mean
that IOV doesn't exist and you will still have problems using such a model
in a TDM program. I do agree there are times when you don't need to
partition out IOV (particularly if IOV is small) but if you know you plan to
use the model in a TDM program that is one of the reasons for evaluating
whether IOV is a big contributor to the total variation.
Ken
Kenneth G. Kowalski
President & CEO
A2PG - Ann Arbor Pharmacometrics Group, Inc.
110 E. Miller Ave., Garden Suite
Ann Arbor, MI 48104
Work: 734-274-8255
Cell: 248-207-5082
Fax: 734-913-0230
[email protected]
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Buclin Thierry
Sent: Monday, November 01, 2010 7:56 AM
To: [email protected]
Subject: [NMusers] Rational of using IOV
Hi Nicolas
My short answer would be another question: "what is the aim of your analysis
?"
IOV is fine to split variability into inter-individual,
intra-individual-inter-occasion and intra-individual-intra-occasion random
components. This is excellent for data description, and can bring
interesting insight into the mechanisms explaining variability. But if you
want to use your results for prediction, e.g. to devise a TDM program, you
won't be able to draw relevant information from IOV: a blood sample obtained
in a patient on a certain occasion won't inform you on your patient's
behavior on another occasion; in this situation, a model merely
distinguishing inter-individual and intra-individual variability components
is easier to exploit. Thus, there may be good reasons not to use IOV even
when it would be possible.
Kind regards
Thierry
Thierry Buclin, MD, PD,
Division of Clinical Pharmacology and Toxicology
University Hospital of Lausanne (CHUV)
Lausanne - SWITZERLAND
tel +41 21 314 42 61
fax +41 21 314 42 66
On 1/11/2010 10:53 a.m., Nicolas SIMON wrote:
Dear colleagues,
could someone give me an advice about the rational of using IOV in a
particular circumstance?
We have data from a clin trial with 3 occasions for each patient. It was a
chemotherapy and the patients have received up to 7 cures. The issue is that
the 3 occasions differ from one patient to another.
Patient X may have be seen on cure 3, 5 and 7 while patient X+1 was seen on
cure 2, 5 and 6 or whatever...
It seems to me that combining the 1st occ of all patients is meaningless (as
for 2nd and 3rd).
Shall we use as many occasions as cures (7 in our dataset)? In that case,
how many patients by occ is relevant as a minimum? For certain occ we may
have few patients. Combining cures is hazardous and has no clinical
justification.
Best regards
Nicolas
Pr Nicolas SIMON
Universite de la Mediterranee (Aix-Marseille II)