Back to the Top
As part of the discussion that is currently going on in a "virtual" meeting
that the Japanese Society of Magnetic Resonance in Medicine has organized on
the Future of MRI/MRS, and where we presented two posters, I have just posted
the following message that I felt was of interest to share with this group.
On Tuesday, 28 Jan 1997 13:06:54 EST, "Jeff F. Dunn"
wrote To: IC97-S3A1.-at-.falcon.osk-teishin.ntt.co.jp re [IC97-S3A1:7]budinger
>1) With respect to clinical spectroscopy, since there is only
>a single voxel technique with FDA approval, American clinicians
>are limited to this method.
FDA approval is gained when there is compelling evidence that a technique has
clinical usefulness. This is case with pharmacokinetic imaging studies of
5-Fluorouracil using 19F-MRS. It is in the interest of patients with breast
and colorectal cancer that such an approval needs to be obtained as soon as
possible. Furthermore, as investigators in other countries (e.g.,
in many European countries, in Japan, etc) do not have the same constraints,
they may be able to use these techniques clinically before we can do so in
the US. I urge the instrument manufacturers in the US to take immediate
steps in gaining such FDA approval.
>3) All high powered MR techniques need justification for
>implimentation as a clinical tool. This justification has to include
>the relative improvement in patient care over other available
>techniques and the proof that the technique will influence the
>patient's outcome.
I agree. If you look at our poster E4, you will see that the association
between trapping and response is rather good (p<.000001). Hence, this is a
method that could (and should) be used NOW to select proper patient management.
Pharmacokinetic Imaging can do much more: it can assess the effect of
modulators, it can determine the degree of potential response of different
metastatic lesions, it can identify longitudinal changes in a patient. As such,
Pharnacokinetic Imaging can help in developing proper therapeutic planning,
rather than the current, non patient specific, methods of administration of
chemotherapy used today.
=========================================================================| Professor Walter Wolf, Ph.D. E-Mail: wwolfw.-a-.hsc.usc.edu |
| Director, Pharmacokinetic Imaging Program |
| Department of Pharmaceutical Sciences Telephone: 213-342-1405 |
| University of Southern California Fax: 213-342-9804 |
| 1985 Zonal Ave., Los Angeles, CA 90033 |
| |
| Center for Noninvasive Pharmacology, Los Angeles Oncologic Institute |
| MRI at St. Vincent Medical Center Telephone: 213-484-7235 |
| 2131 Third St., Los Angeles, CA 90057 Fax: 213-484-7447 |
========================================================================------------------------------
Date: Fri, 31 Jan 1997 15:05:08 -0600
From: Steve Ebert
Subject: Consensus documents
Other organizations (i.e., The Society of Infectious Diseases Pharmacists)
are also working on position papers regarding the utility of monitoring
serum vancomycin concentrations. Anticipated completion of SIDP's paper in
Mid-Summer.
Back to the Top
>PharmPK - Discussions about Pharmacokinetics
>>3) All high powered MR techniques need justification for
>>implimentation as a clinical tool. This justification has to include
>>the relative improvement in patient care over other available
>>techniques and the proof that the technique will influence the
>>patient's outcome.
>
>I agree. If you look at our poster E4, you will see that the association
>between trapping and response is rather good (p<.000001). Hence, this is a
>method that could (and should) be used NOW to select proper patient
>management.
Hi all,
Newby here. It seems to me, the question should be: is the improvement
enough to justify the additional costs to the patient?
-Paul
schlosser.at.ciit.org
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Paul M. Schlosser, Ph.D.
Chemical Industry Institute of Toxicology (CIIT)
P.O. Box 12137
6 Davis Drive (not needed for regular mail)
Research Triangle Park, NC 27709
Voice:(919) 558-1243; FAX:(919) 558-1300; schlosser.aaa.ciit.org
_________________________ _____________________________________
_________________________ | |
_________________________ | ////// //// //// ////////// |
_________________________ | // // // // // // // |
_________________________ | // // // // |
_________________________ | // // // // |
_________________________ | // // // // // |
_________________________ | ////// //// //// //// |
_________________________ |_____________________________________|
Back to the Top
>>PharmPK - Discussions about Pharmacokinetics
>>>3) All high powered MR techniques need justification for
>>>implimentation as a clinical tool. This justification has to include
>>>the relative improvement in patient care over other available
>>>techniques and the proof that the technique will influence the
>>>patient's outcome.
>>
>>I agree. If you look at our poster E4, you will see that the association
>>between trapping and response is rather good (p<.000001). Hence, this is a
>>method that could (and should) be used NOW to select proper patient
>>management.
> Hi all,
> Newby here. It seems to me, the question should be: is the improvement
> enough to justify the additional costs to the patient?
> -Paul
> schlosser.-at-.ciit.org
Hello,
it depends on the viewpoint. If you are a patient, you would like to know
if the treatment used for the colorectal carcinoma is likely to be
effective.
On the other hand, the selection of patients for an individual treatment
protocol can safe money. Example: The modulated treatment protocol with
folinate+FU can only be effective if there is a significant trapping of FU.
We know from the data presented by Walter Wolf (see his message) using MR
spectroscopy, that trapping is required for a sufficient therapeutic
result. Our group was able to demonstrate in patients a close correlation
between the uptake of F-18-FU in liver metastases PRIOR to treatment and
the growth rate of the same metastases DURING treatment
(http://www.dkfz-heidelberg.de/pet/abs_fvol.htm). If you consider the low
average response rates in liver metastases from colorectal tumors and the
high price of the folinate pretreatment it is easy to see that it is very
cost/effective to use noninvasive techniques like MRS and/or PET for the
assessment and prediction of therapy results.
Rgds,
Ludwig
-----------------
Professor of Radiology and Nuclear Medicine
Medical PET Group - Biological Imaging (0510-04)
German Cancer Research Center
Email: l.strauss.-at-.dkfz-heidelberg.de
WWW: http://www.dkfz-heidelberg.de/pet/home.htm
Back to the Top
My presumption was that we are speaking of health care facilities that
already have an MRI unit. I don't know how much can be done with
current units, but I also gathered from the preceding discussion (since
deleted) that this sort of thing was already possible/being done, and
that the proposed changes would "only" improve resolution, rather than
making something possible that could not be done before. The author
says nothing about the "relative improvement."
I also presumed that the upgrade would require the purchase of expensive
new equipment by the hospital, and such expenses do tend to be spread
across all patients.
>A similar argument can be made for the case of the pharmaceutical
>development....
Not quite. In drug development, the company decides whether or not to
spend its *own* money. When a hospital buys a new MRI unit, the expense
goes to patients who then may not be able to choose the "economy model"
(and to those who don't even benefit from the use of it).
-Paul
Back to the Top
On Sun, 9 Feb 1997 10:15:01 -0600
schlosser.-a-.ciit.org (Paul M. Schlosser)
followed up on an ongoing discussion on the use of MRS techniques in
Pharmacokinetic Imaging. My [Prof. Walter Wolf] latest comments are below.
1) MRI is a widely used method, available in all major centers, and most
other clinical facilities than can provide state of the art imaging.
2) Spectroscopy can be done readily with any clinical unit that is 1.5T or
higher.
3) Spectroscopy is different from imaging. The above comment on resolution
appears to be related to an imaging concept, not applicable here.
4) Yes, spectroscopy does indeed make something possible THAT COULD NOT BE
DONE BEFORE. That is the central issue. Spectroscopy allows for a noninvasive
and dynamic chemical analysis of the drugs and their metabolites in human and
animal tumors. That is NOT possible by any other means, at this time.
>I also presumed that the upgrade would require the purchase of expensive
>new equipment by the hospital, and such expenses do tend to be spread
>across all patients.
This assumption is incorrect. The ONLY additional equipment that is needed
are 19F surface coils, which can be manufactured commercially for something
in the ~$5,000 range. The software needed is available from all MRI
manufacturers, and is standard in many systems.
>>A similar argument can be made for the case of the pharmaceutical
>>development....
>Not quite. In drug development, the company decides whether or not to
>spend its *own* money. When a hospital buys a new MRI unit, the expense
>goes to patients who then may not be able to choose the "economy model"
>(and to those who don't even benefit from the use of it).
Yes, and inasmuch as companies spend their own money, they must decide whether
to spend it wisely or not. Our argument is that noninvasive studies are much
more cost effective. Hence, incorporation of good noninvasive studies would
save money, not cost more. Indeed, we have data that suggest that it could
significantly reduce the cost (by many Megabucks!) of an NDA. I will be glad
to discuss this in more detail with anyone interested.
=========================================================================| Professor Walter Wolf, Ph.D. E-Mail: wwolfw.-at-.hsc.usc.edu |
| Director, Pharmacokinetic Imaging Program |
| Department of Pharmaceutical Sciences Telephone: 213-342-1405 |
| University of Southern California Fax: 213-342-9804 |
| 1985 Zonal Ave., Los Angeles, CA 90033 |
| |
| Center for Noninvasive Pharmacology, Los Angeles Oncologic Institute |
| MRI at St. Vincent Medical Center Telephone: 213-484-7235 |
| 2131 Third St., Los Angeles, CA 90057 Fax: 213-484-7447 |
========================================================================------------------------------
Date: Mon, 10 Feb 1997 14:53:45 -0600
From: Pascal.Le-Corre.-a-.univ-rennes1.fr (Pascal Le Corre)
Subject: Aminoglycosides and subcutaneous route
Dear subscriber's
I'm looking for references about the use of aminoglycosides par subcutaneous
route.
Many thanks in advance.
PLC
Pascal A. Le Corre, PhD
Laboratoire de Pharmacie Galenique et Biopharmacie
=46aculte des Sciences Pharmaceutiques et Biologiques
Universite de Rennes 1
2 Avenue du Pr. Leon Bernard
35043 Rennes Cedex
=46rance
Tel. (33) 2 99 33 69 42
Tel. (33) 2 99 33 68 61 (answer serv)
=46ax (33) 2 99 33 68 91
Email Pascal.Le-Corre.-a-.univ-rennes1.fr
Back to the Top
Dear Dr. Schlosser:
Perhaps I was not clear in making the argument for cost
effectiveness for pharmaceutical companies (last paragrapoh of this e-mail).
Yes, you are correct when you say that
the hospitals make these purchases, not the pahrmaceutical companies(except
when
the pharmaceutical companies make donations to the hospitals for the
purchase of MRI systems!)
The point I was trying to make is, that since the pharmaceutical companies
will have to pay for the scans that are part of their protocol, it is, in
fact, their *own*
money; money that would be well-spent in helping the company to ultimatley make
importnat decisions on how to proceed with their drug development.
"A similar argument can be made for the case of the pharmaceutical
development. Where drug development from concept to registration is
approx. $300 Million, a non-invasive technique that permits the analysis
of pharmacokinetics at the target tissue can, as Dr. Wolf
demonstrated, provide important information during clinical trials
that can help pharmaceutical companies improve their data quality and
increase their chances for success."
Yours truly,
Michael Silver
Back to the Top
Dr. Wolf:
>1) MRI is a widely used method, available in all major centers, and most
>other clinical facilities than can provide state of the art imaging.
I know, I've had the pleasure of lying in one.
>2) Spectroscopy can be done readily with any clinical unit that is 1.5T or
>higher.
>3) Spectroscopy is different from imaging. The above comment on resolution
>appears to be related to an imaging concept, not applicable here.
>4) Yes, spectroscopy does indeed make something possible THAT COULD NOT BE
>DONE BEFORE. That is the central issue. Spectroscopy allows for a noninvasive
>and dynamic chemical analysis of the drugs and their metabolites in human and
>animal tumors. That is NOT possible by any other means, at this time.
I did some spectroscopy, once upon a time (~ 8 years ago), so this seemed
to be more of an "upgrade" on what was possible back then, and it that
sense was not novel.
>This assumption is incorrect. The ONLY additional equipment that is needed
>are 19F surface coils, which can be manufactured commercially for something
>in the ~$5,000 range. The software needed is available from all MRI
>manufacturers, and is standard in many systems.
Which is a fair chunk from an academic budget, but I agree it's nominal
for a hospital--this was the "data" that was missing from the "MUST be
used" statement.
>Yes, and inasmuch as companies spend their own money, they must decide whether
>to spend it wisely or not. Our argument is that noninvasive studies are much
>more cost effective. Hence, incorporation of good noninvasive studies would
>save money, not cost more. Indeed, we have data that suggest that it could
>significantly reduce the cost (by many Megabucks!) of an NDA. I will be glad
>to discuss this in more detail with anyone interested.
But the original post only presented the fact that resolution had been
improved, and did not present these other facts, and implied that improved
resolution in and of itself was sufficient motivation. This is exactly
what was mising.
Regards,
-Paul
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
ON MATERIALISM
He who dies with the most toys, is, nonetheless, still dead.
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)