For some, untested drug is a last chance
For some, drug is last chance
About 2 1/2 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 Burroughses begged the manufacturers, ImClone and AstraZeneca, respectively, to give Abigail 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 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 current 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.
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 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 pay manufacturers for the drugs, an issue that opens a Pandora's box of ethical and liability questions.
Despite its powerful emotional appeal, the Tier 1 plan is creating a firestorm of opposition.
"We have a system in place to prove the safety and efficacy of therapies. We can't afford to undermine that system," said Fran Visco, president of the Washington-based National Breast Cancer Coalition.
Visco noted 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.
Nancy Roach, a director of the Marti Nelson Cancer Foundation based in Vacaville, Calif., also opposes the Tier 1 idea, saying, "It would rip the heart out of clinical research."
At the end of a Phase I (safety trial), a drug may have been tested in only a few dozen people. (It is not until 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," she said.
Dr. Marcia Angell, a medical ethicist and a former editor of the New England Journal of Medicine and senior lecturer on social medicine at Harvard Medical School, also opposes the Tier 1 idea. "New drugs are far more likely to fail than to succeed," she said, "so the chances are that a patient will be hurt by a drug rather than helped."
She said she also is appalled that patients might end up paying manufacturers for experimental drugs. Drug companies already "are profitable beyond any industry," she said. "They are protected by the government.
They have monopoly rights, patents, tremendous tax breaks." And the opposition doesn't stop there. Alan Goldhammer, associate vice president for regulatory affairs for the Pharmaceutical Research and Manufacturers of America, said it would be "potentially reckless" for manufacturers to release drugs after only Phase I trials because at that point there is "no proof of efficacy at all."
The FDA won't comment on the lawsuit per se, but spokesperson Terry Toigo said: "We're always looking to hear from people about ideas on where our system doesn't work."
The trouble is, for many seriously ill patients like Abigail Burroughs, the current system doesn't work.
It takes at least 10 years (and $800 million) for the average drug to survive all three phases of approval. Many patients can't wait that long, and 80 percent of drugs fail along the way.
In addition to joining a clinical trial, there are only a few ways to cut the waiting time, and they're complicated. Under the "compassionate-use" system, a doctor may 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.
Under the "expanded-access" program, 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. If there are more patients than drugs available, the company may set up a lottery.
Companies can also try to rush drugs through the FDA under the "accelerated-approval" program, getting approval on the basis of "surrogate markers," such as tumor regression, rather than demonstrated clinical benefit, such as increased survival.
Companies may 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 works well enough. But for others, like Ruth-Ann Santino of Arlington, it doesn't. Two years ago, Santino "wrote the world" to put pressure on ImClone to give her Erbitux, said her husband, Fred Santino. But she never got the drug, and died in May 2001 of colon cancer.
Judy Foreman can be contacted at firstname.lastname@example.org.
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