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HEALTH
Trials and Tribulations
A primer on the FDA's drug approval process
by Jim Dean
Beginning this issue
Southern Voice is pleased to be
able to publish information gathered
by the Treatment Advisory
Committee of the Atlanta Chapter of
the National Association of People
With AIDS. The next update will
appear in issue #16 and focus on
AZT, ddi and ddc.
Emotions run high whenever we hear
of a new drug for treatment of an HIV-
related condition. Trying to keep the ter
minology relating to new drugs straight
(so to speak) and understand the myriad
changes in guidelines gives me a major
headache.
So, I volunteered to write this article
to educate myself and hopefully help
make this subject less confusing for
Southern Voice's readers. The material
condensed here is from an FDA
Consumer Special Report. Operation of
the Food and Drug Administration falls
under the U.S. Department of Health and
Human Services; it is the watchdog that
is supposed to insure the safety of our
drug and food supplies. The infamous
National Institutes of Health (NIH) is its
sister agency.
The FDA's newest drug development
process is made of four major stages
which, on average, require 100 months
to complete. Understand, please that I
am not advocating this process, but
hopefully clarifying it.
First, there's Pre-Clinical. This
stage covers the initial making of the
drug and most animal trials. If the drug is
seen to have the desired effect in the test
tube, then animal trials begin. Two
species of animals are used. Dosages and
toxic effects are evaluated for the human
trials that will follow. Pre-clinical's take
1-3 years, averaging 18 months, plus a
30-day safety review prior to any human
testing.
This part of the process is very costly
for the drug company; bringing a drug to
market may cost $65-125 million. All
cost figures are created by the drug com
panies, however, and, as such, may be
somewhat biased.
Some drugs prove too harmful—or
not helpful—to humans during these tri
als. These drugs are shelved, but can be
pulled out at a later date if an apparent
need arises. AZT—developed as a poten
tial cancer drug in 1964 and shelved due
to ineffectiveness—was approved as an
anti-viral agent to fight AIDS in 1987,
three years after pre-clinical trials were
resumed for its new purpose.
Before the first human takes a drug,
certain information is required by the
FDA. The drug company provides this
information by submitting an IND, or
Investigational New Drug application.
The IND includes the results of all
animal and laboratory research plus any
information on prior human usage, either
in this country or abroad.
The drug company must also submit a
detailed report on: how the clinical trials
will be conducted; how many people will
be involved; how they will be selected;
where the studies will be done; who will
do the studies; how safety and effective
ness will be evaluated; and finally, what
finding would require the study to be
stopped or changed. Clinical trials may
begin only after the FDA's approval of
the IND.
The Clinical trials are usually done in
three phases.
Phase I: Usually lasting several
months, it is primarily concerned with
safety issues. The volunteers, usually
healthy, are given a variety of tests to
discover what happens to the drug in the
human body. Seventy percent of drugs
make it through Phase I; failures fre
quently result from too much toxicity in
too small a dosage to be of benefit.
Phase II: Focused on treating the
disease and involving several hundred
volunteers, Phase II judges the side
effects of the drug on health-impaired
people. Trials are randomized and con
trolled, meaning the group being treated
with the drug is matched with a group
similar in make-up (i.e. sex, age, disease
state). The matched groups receive either
a placebo or the drug being tested, but
neither the subjects nor the researchers
know who receives which. This takes
several months to 2 years; about one
third of drugs make it through.
Phase III: These trials may involve
as many as several thousand participants
and generally last 1-4 years.
Occasionally, a drug is proved so suc
cessful in Phase II that Phase III is
skipped. This was the case with AZT.
During its Phase II trial, only one indi
vidual receiving AZT died, compared to
19 taking the placebo.
The use of placebos and animal test
ing remains controversial and may be
considered unethical in diseases like
AIDS where the need for new therapies
is so urgent.
Following the Clinical Trials, the
drug is submitted to the FDA for
approval. Review by the FDA and the
drug company may last from 2 months to
7 years. By this point, the volumes of
documentation on each drug may fill an
entire room.
Because of pressure from both AIDS
activists and medical communities,
change in this process is being consid
ered. AZT received the fastest approval
ever given by the FDA, 4 months. But
this was partially due to the drug's previ
ous testing—Phase III was eliminated
and the review process drastically
reduced. The FDA is currently involved
in an elaborate surveillance of studies on
AZT in order to gather the information
that would have come from Phase III
studies.
Earlier this month, a committee of
the President's Cancer Panel, charged
with reviewing FDA procedures for
approval of cancer and AIDS drugs, sub
mitted a report which said "years" could
be cut from these procedures. The com
mittee made a number of recommenda
tions, insisting that the FDA exercise its
"flexibility" to ensure AIDS and cancer
patients access to drugs that may help
them as early in the review process as
possible. The committee indicated that
FDA approval of a new drug should look
at the potential for that drug to improve a
patient's quality of life, not just its ability
to prolong life.
Directory Provides
Survey of AIDS
Trials and Research
It's free to PWA's
In a format that is readable and
accessible—though necessarily
technical—the AIDS/HIV
Treatment Directory lists trials of
promising drugs that are currently
recruiting new patients. It also
includes listings of drug manufac
turers, trial centers, informational
resources and physician investiga
tors all over the country.
The 120-page book also contains
descriptions of numerous drugs,
including trial results on their effec
tiveness and toxicity, and a glossary.
Essays and articles by scientists at
the forefront of AIDS research
round out each issue.
The directory is provided free to
people with AIDS who cannot
afford the subscription. But anyone
affected by the epidemic-
researchers, physicians, and the
friends, families and lovers of peo
ple with HIV—will find it informa
tive and beneficial.
One year subscriptions are $30.
Contact AmFAR at 1515 Broadway,
Suite 3601, New York, NY 10036
8901 for further information.
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Southern Voice/August 30, 1990
17