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.