July 26, 2006
Hearing Slated for von Eschenbach
The Senate Health, Education, Labor and Pensions Committee will hold a hearing next Tuesday on whether Dr. Andrew von Eschenbach's appointment to head the Food and Drug Administration should be made permanent. The headlines will be dominated by his stance on Plan B, the over-the-counter morning-after pill. Senators Hillary Clinton and Patty Murray are threatening to hold up his approval unless he lets the FDA scientists call the shots on this one -- not the religious right.
I hope the Senators also look into the question of conflicts of interest stemming frmo his tenure as head of the National Cancer Institute. NCI, as I've pointed out numerous times in this space, has a structural conflict with FDA since one of its jobs is to bring new therapies to market, which the FDA must approve. The public has been repeatedly told that von Eschenbach has severed his ties with NCI and now that he is at FDA, he will recuse himself in any matters that he worked on during his years at the cancer research shop.
Yet how do you explain this listing on the Health and Human Services Department website? It says he is still an employee of NCI. And if you go here, you'll see he's also listed as an employee of FDA. The Senators might want to ask him about that.
Posted by gooznews at July 26, 2006 12:46 PMIt shows that HHS is slow to update their directory.
I looked for a couple people who left HHS a couple months ago... actually one left four months ago...and they are both in there.
Posted by: Scottie at July 26, 2006 05:44 PMYou're probably right. But they should still press him on the issues he's recused himself from. Having a new drug advocate at the top of the FDA is troubling, moreso, in my view, than the non-handling of Plan B.
Posted by: Merrill at July 26, 2006 09:09 PMYou are right on that one.
Von Eschenbach should grilled on Plan B. Of course, the WH is probably laughing at playing the role of Lucy..pulling the Plan B football away from Hilary Clinton's Charlie Brown. "okay...this time I am really going to let the scientists make the decision...."
Yes, he should also be asked about his recusals...and someone should seriously think about whether anyone who says stupid unsupportable things like curing cancer by 2015 is qualified for the position.
But one has to wonder whether von Eschenbach appointment is only just the symptom...that the "approve everything faster" party has already started with the people in place in the agency, department and WH..and he is just joining late.
Posted by: scottie at July 26, 2006 10:06 PMI would like a formal response from the FDA why better liver toxicity testing is not used. It should be important to find developing toxicity problems early and not wait and help only those in need of a transplant. I have included my responses from both the FDA and the CDER, but neither answers the question of why a better test is not used or promoted. Since these memos I have provided additional information, with no reply from the FDA. LDH Isoenzymes are such a sensitive test method that you can find liver problems before the absolute value of any of the liver enzyme tests are abnormal.
Before I discuss the need for better tests with the media, I would like an on-the-record-comment from the FDA. I also provided information on a better method for cancer detection. This method will be used in a documentary film showing the effectiveness of cancer treatments. Please ask the FDA to provide a comment on this testing also.
Researchers who I have been in contact with, including those below, have provided only one reason: that early detection does not fit their project scope - this is not a reason not use the testing in clinical drug trials.
Alastair Wood - Vanderbilt
P. B. Watkins - UNC (DILIN)
K. E. Gavin - University of Michigan (DILIN)
C. C. Mathis (C-PATH)
George Morris
407-227-7074
Dear Mr. Morris:
Thank your for your inquiry to the Division of Drug Information at the
Food and Drug Administration.
I apologize in my delayed response, I was consulting with a
toxicologist for a response. Her response is as follows:
LDH isoenzymes are still used occasionally in clinical medicine where
elevations are seen but, for some reason, not accompanied by ALT
elevations, etc. LDH isoenzymes are of limited value, however, since this
situation is unusual, and the technology hasn't been improved for years.
It's really an antiquated assay of limited utility - it doesn't really
tell you anything unique, and is not an especially sensitive assay.
Division of Drug Information
Center of Drug Evaluation and Research
Food and Drug Administration
kcd
This communication is consistent with 21 CFR 10.85 (k) and constitutes
an informal communication that represents our best judgment at this time
but does not constitute an advisory opinion, does not necessarily
represent the formal position of FDA, and does not bind or otherwise
obligate or commit the agency to the views expressed
-----Original Message-----
From: georgemorris74@earthlink.net [mailto:georgemorris74@earthlink.net]
Sent: Tuesday, April 25, 2006 6:22 PM
To: CDER DRUG INFO
Subject: DrugInfo Comment Form FDA/CDER Site
Name: George Morris
E-Mail: georgemorris74@earthlink.net
Comments: Why are these liver toxicity tests not in use?
-----Original Message-----
From: Flammang, Thomas [mailto:thomas.flammang@fda.hhs.gov]
Sent: Wednesday, April 26, 2006 10:47 AM
To: 'georgemorris74@earthlink.net'
Cc: Huber, Rose
Subject: LDH and Liver Toxicity Testing
Dear Mr. Morris,
I am a biochemist and not a medical doctor but here are some probable
answers to your question from the standpoint of biochemistry. I suggest
that you consult with a liver doctor (Hepatologist) or visit a medical
library for a more up to date text on clinical chemistry and toxicology to
satisfy your curiosity.
It is true that several dehydrogenases, including LDH, have been used in
the past as a screening test for liver injury. However as medical knowledge
has advance phenomenally in the thirty since your citations, it has been
realized that measuring LDH levels for indicating liver injury has limited
value both because it is present in so many different tissues and that the
isoenzymes activity (LDH-5 and LDH-4 are isoenzymes) vary considerably among
species. You can see that you could conclude a liver toxicity from the
test, but be completely wrong. For instance, the LDH measurement may be
more commonly used in combination of measurements of other enzymes (e.g.,
CK, AST and ALT)to indicate heart damage and congestive heart failure...but
even at that, several other medical tests might be performed by a
cardiologist to be sure there is really heart damage; for example an
electrocardiogram.
Sincerely,
Tom Flammang
-----Original Message-----
From: George Morris [mailto:georgemorris74@earthlink.net]
Sent: Tuesday, April 25, 2006 5:34 PM
To: Huber, Rose
Subject: Liver Toxicity Testing
Why are these liver toxicity tests not in use?
In the early 1970's researches used both diseased and normal population
in their clinical studies of isoenzymes. In the study:
CHARACTERIZATION OF ALKALINE PHOSPHATASE IN SERUM BY AGAR GEL
BY Lars Sundbald, Marta Nilsson, and Johan Brohult
Clinica Chimica Acta, 45(1973) 219-223
On page 220 under the heading
"Lactate dehydrogenase
(LDH) isoenzymes were measured by agar gel electrophoresis method of
Wieme with slight modifications. By this method a mean LDH-5/LDH-4
ration of 0.75(plus or minus 0.15)(mean SD) was found for 62 healthy
persons (laboratory staff, medical students). A LDH-5/LDH-4 ratio
exceeding 1.0 is in the present study taken as indicative of liver
injury. NOTE: A ratio was used to identify liver injury (toxicity)
Other references of using the ratio for liver injury:
Clin Chim Acta, 1977 April 15; 76(2):205-11
Book - Clinical Medicine 1978 Vol 1 Chapter 27 pages 47-49
Elevated LDH-5 Isoenzyme. Relative (and absolute) elevation of LDH-5
isoenzyme is classically associated with liver disease (Fig 27-37).
George Morris, cellular 407-227-7074