ABIGAIL BURROUGHS, a 21-year-old American, died from squamous-cell carcinoma of the head and neck in 2001. According to her father, Frank, she didn’t need to die. There were drugs in development that might have reined in the malignancy, but the experimental therapies were being tested on cancers in other parts of the body.
“She had the right cells in the wrong place, and she didn’t qualify for any of the clinical trials,” her father recalls. Shortly after her death, he founded the Abigail Alliance for Better Access to Experimental Drugs. This summer it scored a breathtaking victory in the courts against the Food and Drug Administration. The District of Columbia Circuit ruled, by two to one, that a patient with a terminal illness or untreatable disease had a “fundamental right” under the Constitution to experimental drugs that have passed only preliminary (Phase I) tests, and are thus a long way from approval.
The little-reported decision is already having deep repercussions in the medical world, and is likely to end up in the Supreme Court. While patients welcome the decision, regulators and clinical researchers fear that such early, wide access to experimental drugs will make it harder to obtain the clear, long-term data needed to prove efficacy. Patients may decide an unproven drug is a better gamble than ending up on a proven, but marginally effective, medication. An article in the New England Journal of Medicine this month points out that only 11 per cent of drugs — and only 6 per cent of cancer drugs — that enter clinical testing are ultimately approved; the rest are either too toxic or don’t work.
Colin Begg, a biostatistician at the Memorial Sloan-Kettering Cancer Centre and board member of the Society for Clinical Trials, tells NEJM that, if the legal ruling stands, “the market would be flooded with drugs and we wouldn’t have any idea which ones were effective. It would ultimately be very bad for patients.” Bruce Chabner, clinical director of the Cancer Centre at Massachusetts General Hospital, Boston, is similarly bewildered: “I don’t have a right to fly somebody’s experimental airplane, so why should I have the right to some drug that a company has dreamed up?”
There is already limited scope for giving experimental therapies to very sick patients on a compassionate-use basis. This, however, generally happens when the drug is at the Phase III stage and thus much closer to market. Crucially, there has been no obligation on either the doctor to apply for the medication on behalf of his patient, or on the drugs company to provide it.
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The court decision prompted by the Abigail Alliance means that a refusal to provide experimental drugs would now violate a patient’s constitutional rights. The legal arguments were long and complex; one factor was that the right to self-preservation took precedence over the FDA’s right to regulate access to drugs. Curtailing the powers of the FDA in this way also chimes with the current fashion for deregulation.
Conflicting beliefs were argued with equal conviction by both sides. “The prerogative asserted by the FDA — to prevent a terminally ill patient from using potentially life-saving medication to which those in Phase II clinical trials have access . . . impinges upon an individual liberty deeply rooted in our nation’s history and tradition of self-preservation,” concluded Judge Judith Roberts.
Thomas Griffith, the dissenting judge, said: “I have serious doubt about how a court can know, as a matter of constitutional law, that the lesser of two evils will be achieved by providing all terminally ill patients access to all Phase I experimental drugs, given the risks these drugs present.”
I’m not a clinician. I have twice sought anti-cancer drugs for friends on a compassionate-use basis (one was Iressa, the same drug sought by Frank Burroughs). Yet my instinct tells me that Judge Griffith is probably right, and the legal decision, though rich in compassion, is thin on wisdom. Extending the capacity for compassionate prescribing, and encouraging more patients to join clinical trials (only one in 20 cancer patients opts in), seem better options.
Drug trials are long and laborious for a reason: reliable clinical evidence is not easily or quickly accrued. To allow patients to demand a Phase I drug is more likely to stall than to speed clinical progress.