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FDA Trials Cost Lives

Submitted by: John Warner on Apr 03, 2002 at 6:00 am Tagged with: General Archives Source:

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April 3, 2002
The Wall Street Journal COMMENTARY
FDA Trials Cost Lives
By ROBERT OLDHAM
Non-Hodgkins lymphoma (NHL) is an increasingly frequent, incurable cancer of
the lymph nodes which often spreads to other organs. Approximately 54,000
Americans will be diagnosed with NHL this year, and as many as 25,000 will die
from it. NHL is one of the most frequent killers of 20-to-39-year-old men. A
subset of NHL called follicular lymphoma has an average survival time of some
seven to eight years but is ultimately incurable, resulting in 4,000 to 5,000
deaths each year. That's the bad news.
The good news is that new biologically based, personalized treatments, rather
than one-size-fits-all chemotherapy, have an excellent likelihood of
effectively treating this cancer -- to the point of possibly curing follicular
lymphoma.
Sounds promising, so what's the problem? The problem is the Food and Drug
Administration, the agency that approves all new cancer treatments. If the FDA
applies its usual standard of a randomized clinical trial to prove "once and
for all" that this new treatment works, it will not be available to all NHL
patients who need it; thousands will die while the FDA awaits proof of its
efficacy.
Sadly, this isn't unique to NHL. For all our medical advancements, we seem to
accept the notion that needless deaths must occur to bring a promising new
treatment to those in need. This simply isn't the case. In fact, there are many
ways our drug development methods and the FDA could be made more efficient. A
closer examination of NHL and its treatment will help to illustrate this point.
Lymphomas are composed of cells called lymphocytes, which in their normal state
are part of our immune system, helping the body fight infection and cancer.
Each begins as a single cell "gone bad," which through growth and reproduction
ultimately becomes a mass of cells we call lymphoma. Since all the cancer is
from one cell and since lymphocytes have the property of expressing a unique
protein on their surface, called an "idiotype," we have a specific cancer
marker or target to attack.
For 30 years, scientists have been studying this target, and making antibodies
against it -- so-called anti-idiotype antibodies. In 1999, a landmark study of
a cancer vaccine demonstrated that 90% of the 22 NHL patients who received it
had long remissions, and 77% were in remission up to 74 months post treatment
(as of 2001). This therapy yielded "molecular remissions," never seen with
chemotherapy alone, where the cancer cell bearing the idiotype was completely
eliminated as determined by the most sensitive test now available. This vaccine
uses the idiotype protein to immunize patients against their own cancer, in
effect using their own cancer cells to effectively treat and possibly cure
their cancer.
Given the encouraging, long-term results of this study and others, the National
Cancer Institute -- with FDA guidance and consent -- is now planning an
extensive, five-year, random clinical trial of the vaccine. The trial will
include 563 patients; half will receive the active vaccine and half a vaccine
with no known activity in lymphoma patients. Not only will 282 participants in
the trial be denied the active vaccine, 4,000 NHL patients will die each year
during the study without ever having the opportunity to try the vaccine.
This sort of study is not only unfair, it's outdated. It simply does not make
ethical or scientific sense to apply a drug development paradigm developed
decades ago for drugs designed for large populations of patients to these new,
personalized medicines developed from the patient's own tissues. A better
alternative would be to allow these individualized cancer therapies to be
prepared by biotechnology companies under the guidance of experienced
oncologists. One could then judge their long-term effectiveness by standard
clinical means, such as comparing results to patients treated concomitantly or
in the past with other therapies.
Randomized trials are essential in the search for minor variations in patient
response to treatments. But when major improvements in treatment exist and can
be made available, it is neither reasonable nor ethical to carry out such
studies. Ask any patient, would you rather have chemotherapy alone with an
assured fatal outcome, or would you rather receive chemotherapy plus a
personalized vaccine where at least 50% of the patients will be alive and in
remission five years later?
The new FDA commissioner -- whoever it is -- should immediately change
procedures or ask for legislation to encourage the more rapid development and
approval of personalized therapies to those in peril. We must calculate the
lives lost and improve the system so these new, less toxic, more effective,
personal medicines can be made available now.
Dr. Oldham is chairman of the South Carolina Biotechnology Association and CEO
of Cancer Therapeutics Inc.