Terminally-ill patients in the USA have lost their long-running battle for the right to be treated with experimental new drugs. Last week, the US Supreme Court turned down a request for it to review earlier court rejections of the claim by the Abigail Alliance for Better Access to Developmental Drugs that “a terminally-ill patient with no approved treatment options has a right to decide for himself, in consultation with his own doctor, whether to take a drug that the FDA concedes is safe and promising enough to be tested in substantial numbers of human subjects.”

The Alliance, which began its court battle in 2003, is headed by Frank Burroughs, whose daughter Abigail died in 2001 aged 21 from head and neck cancers. In the months before her death, she had petitioned the Food and Drug Administration, unsuccessfully, to receive ImClone’s Erbitux (cetuximab), then in clinical trials and which her oncologist had recommended for her. Erbitux was approved by the FDA in 2004. “Huge numbers of Americans die each year after being denied access to developmental drugs that might have prolonged their lives - drugs that, in many instances, later received FDA marketing approval,” say Alliance spokesmen.

Earlier this month, the Alliance and the Washington Legal Foundation asked the Supreme Court to overturn a ruling by the US Court of Appeals for the DC Circuit, which concluded last summer that “there is no fundamental right, ‘deeply rooted in this nation's history and tradition,’ of access to experimental drugs for the terminally ill.”

The Bush administration and the FDA had urged the Supreme Court not to hear the case. In a brief filed with the court, Solicitor General Paul Clement acknowledged that patients suffering from serious diseases "have an understandable interest in trying potentially effective investigational drugs, particularly when the patient's illness is life-threatening.”

However, he added: “allowing patients to obtain and use unproven drugs carries a host of risks and potential detriments for the public health.” FDA studies have shown that preliminary expectations of safety and efficacy "often prove to be unfounded, and drugs that initially appear promising are frequently found ineffective or even affirmatively dangerous to life and health,” he warned.

Successful clinical trials are the exception, not the rule, as the great majority of drugs will ultimately provide no benefit, the Solicitor General told the court. For example, only 5% of all cancer drugs that begin clinical testing are ultimately approved, and even among those that successfully complete Phase I testing, less than a third proceed from Phase II to Phase III. “Thus, when investigational drugs are fully tested by the FDA’s clinical trial process, the expectations regarding safety and efficacy that led the sponsor to initiate the process commonly prove to be unfounded,” he said.

Expanded access
Mr Clement also pointed to the FDA’s expanded access programme, which allows patients to seek access to investigational drugs before the sponsor has completed the clinical trial process and the agency has determined the drug to be safe and effective. “The FDA, acting in concert with Congress, has developed a variety of mechanisms for making investigational drugs available for treatment uses during the course of ongoing clinical trials,” he said.

The Alliance told the Supreme Court that too many patients cannot get into drug trials “because they are too young, too sick, cannot qualify for the trial protocol, cannot travel or because the trial is simply too small.” Their only option, and for those who cannot enrol in expanded-access programmes, is to persuade the FDA that the benefits of receiving an experimental treatment outweighs the risks. However, this process requires “a mountain of regulatory paperwork” and only about 70 patients each year are successful, said the Allliance, although the Bush administration claimed that the FDA approves “nearly all” such patient applications.

After the Supreme Court rejected their petition, Alliance spokesman said that bringing a new lawsuit was an option, and they are also campaigning to get the existing legal situation changed.

In late 2006, the FDA began developing a Proposed Rule on Expanded Access to Investigational Drugs for Treatment Use which, it says, “is intended to improve access to investigational drugs for patients with serious or immediately life-threatening diseases or conditions, who lack other therapeutic options and who may benefit from such therapies.”