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Parents
Fight for Experimental Drugs Two and
a half years ago, several months before she died, Abigail
Burroughs, a 21-year old senior at the University of Virginia, sat
with her father as chemotherapy dripped, once again, into her
body. Together, they mapped out a plan they hoped would save
Abigail’s life, and the lives of other desperately-ill people. Burroughs,
who was diagnosed with head and neck cancer at 19, had taken every
medication her doctors could think of, to no avail. Her last
chance, she believed, might be two experimental drugs, Erbitux
(still not approved by the US Food and Drug Administration) and
Iressa, approved in May. The
Burroughs begged the manufacturers, ImClone and AstraZeneca,
respectively, to give her the drugs on a “compassionate use”
basis, but ImClone
said did not have such a program at that
time. (It does now.) And
AstraZeneca, which was giving Iressa free to 22,000 people
with lung cancer, said no because Abigail had the wrong kind of
cancer. These
drugs might not have helped Abigail. But she and her father,
Frank, became convinced that seriously ill people should be
allowed to get– and even pay manufacturers for – experimental
drugs once they have passed preliminary (Phase I) safety trials in
humans, even if the drugs might turn out to be dangerous, or
useless. In their
view, the currently-available ways to get experimental drugs
– through clinical trials,
“compassionate use” or “expanded access” programs -
are tragically inadequate. So this
summer, Frank Burroughs, who now heads the Abigail Alliance for
Better Access to Developmental Drugs, teamed up with the
Washington Legal Foundation and sued the FDA to loosen its rules. They
want the FDA to create a new level of review called Tier 1 Initial
Approval. Under this plan, patients would be able to get an
experimental drug if it drug has passed Phase I trials, if the
patient has been rejected from clinical trials of the drug, and if
nothing else has worked. Perhaps most controversially, they also
want to allow patients to be allowed to pay manufacturers for
these minimally-tested medications. Despite
its powerful emotional appeal, the Tier 1 plan is creating a
firestorm of opposition, including from other patient advocacy
groups. Fran
Visco, president of the National Breast Cancer Coalition based in
Washington, D.C., says, “We have a system in place to prove the
safety and efficacy of therapies. We can’t afford to undermine
that system. The system is premised on [the idea that] drugs
should not be available until they are proven safe and effective.
” Visco
points to two notorious instances in which medical interventions
became widely used without adequate testing and later proved to be
harmful or ineffective: bone marrow transplantation for breast
cancer and hormone replacement therapy for menopause. Asked
whether an individual should nonetheless be free to choose his or
her own risks, she is emphatic. “When you start talking public
policy, decisions have to be made. It’s not on the individual
autonomy level.” Nancy
Roach, a director of the Marti Nelson Cancer Foundation based in
Vacaville, CA, also opposes the Tier 1 idea, saying “it would
rip the heart out of clinical research,” adding “these drugs
are not candy, they are not harmless.” At the
end of a Phase I (safety trial), a drug may have been tested in
only a few dozen people, she notes. (It is not until larger Phase
II and Phase III trials that a drug is tested in more people and
researchers study dosages and efficacy.)
“You don’t give drugs to people unless there’s a good
reason to, you know how to give them, and the person has some
chance of benefiting,” argues Roach. Medical ethicist Dr. Marcia Angell, the former editor of the New England Journal of Medicine and senior lecturer on social medicine at Harvard Medical School, is also opposes to the Tier 1 idea. “New drugs are far more likely to fail than to succeed, so the chances are that a patient will be hurt by a drug rather than helped,” she says. She also rejects the idea that manufacturers need financial incentives to release them. Drug companies already “are profitable beyond any industry,” she says. “They are protected by the government. They have monopoly rights, patents, tremendous tax breaks.” The
pharmaceutical industry also vehemently opposes the Tier 1 idea.
Alan Goldhammer, associate vice president for regulatory affairs
for the Pharmaceutical Research and Manufacturers of America, says
it would be “potentially reckless” to release drugs after only
Phase I trials because at that point there is “no proof of
efficacy at all.” There could also, he adds, “be potential
product liability issues.” At the
FDA, Terry Toigo, director of the office of special health issues,
says the agency has no comment on the lawsuit but adds, “We’re
always looking to hear from people about ideas on where our system
doesn’t work.” For
seriously ill patients like Abigail Burroughs, there are many
parts of the system that don’t work. It
takes at least 10 years (and $800 million) for the average drug to
pass through Phase I, II and III clinical trials en route to full
market approval. Many patients can’t wait that long, and four
out of five drugs fail along the way. In
addition to joining a clinical trial
(which can be hard to get into for medical or geographic
reasons), there are a few ways to cut the waiting time, but they
involve navigating a complex, bureaucratic maze. Under
“compassionate use,” also called a single patient IND
(for investigational new drug), a doctor can write the
manufacturer asking for a specific drug for a specific patient.
The FDA reviews this request and usually approves. The company may
then – but does not have to – give the drug to the patient. Another
route is the expanded access” program, in which a drug maker
develops a protocol for giving the drug to an entire group of
patients who meet medical criteria. If the FDA approves, the
company then enrolls patients, but often there are more patients
than drug available, in which case the company may set up a
lottery. Drug makers can charge for “cost recovery” but
usually don’t. Companies
can also try to rush drugs through the FDA under the
“accelerated approval” program, as occurred with
AstraZeneca’s Iressa. In
this scenario, the company gets approval on the basis of
“surrogate markers,” such as regression of a tumor, rather
than demonstrated clinical benefit, such as increased survival. Companies
can also ask for a “priority review” if a new drug would be a
significant improvement over drugs already on the market. And they
can “fast track” a drug by submitting data on a rolling
timetable, as the research marches along, not just at the end of
the process. For
many patients, this system works well enough. For others,
including Ruth-Ann Santino of Arlington, it doesn’t. Two years
ago, Santino “wrote the world” to put pressure on ImClone to
give her Erbitux, says her husband, Fred Santino. The Santinos
even heard of another patient who appeared to have gotten the drug from
ImClone. But Ruth-Ann Santino never did. She died in May, 2001. Judy
Foreman is a Lecturer on Medicine at Harvard Medical School and an
Affiliated Scholar at the Women’s Studies Research Center at
Brandeis University. Her
column appears every other week. Past columns are available on www.myhealthsense.com.
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