• 2/19/2007
  • Springfield, MA
  • Robert Cohen
  • The Republican (www.masslive.com)

Abigail Burroughs fought head and neck cancer for 18 months, desperately seeking access to promising experimental drugs after chemotherapy and radiation therapy failed.

She was unable to get into a clinical trial for ImClone’s now widely available Erbitux, because it was for colon cancer patients only, and she failed to meet the clinical trial inclusion criteria for Iressa, an AstraZeneca cancer drug that later proved largely unsuccessful.

At the end of May 2001, Burroughs was finally accepted into a clinical trial for OSI Pharmaceutical’s subsequently approved cancer drug Tarceva, but she was too ill to travel from Virginia to the Texas testing site. She died two weeks later at age 21.

“It was a horrible, horrible nightmare. When your child is terminally ill, you want to do everything you can,” said her father, Frank Burroughs of Fredericksburg, Va. “People just want a chance to live when they are facing death.”

Burroughs soon formed the Abigail Alliance, an organization dedicated to helping cancer patients and others with life-threatening illnesses break down barriers imposed by the Food and Drug Administration and the pharmaceutical industry to obtaining potentially helpful experimental drugs outside the clinical trial setting.

His relentless campaign has resulted in a court ruling that threatens to shake the foundations of the FDA’s regulatory authority covering pharmaceuticals and lead to greatly expanded use of unapproved medications that haven’t been fully tested for safety or effectiveness.

The legal battle, ironically, comes as medical experts, members of Congress and consumer groups have been criticizing the FDA for letting problem drugs on the market and then not properly monitoring their safety.

In a case to be reargued March 1 before 10 members of the U.S. Court of Appeals for the District of Columbia, a three-judge panel last May ruled dying patients have a constitutional right to purchase unapproved experimental drugs that have completed the initial Phase I human clinical testing if their doctors say there are no other viable options.

Just as terminally ill patients have a right to die by refusing medical treatment, the court said in a 2-1 decision, individuals have a fundamental right to “self preservation” that includes being able to obtain potentially life-saving drugs in early stages of clinical development.

The FDA is vigorously contesting what it calls “a profoundly troubling ruling,” arguing the appeals court has placed its ability to ensure patient safety in “a constitutional straight jacket.”

By weakening its discretionary authority, loosening the standards and allowing large numbers of patients to take drugs after small Phase I trials, the FDA said, the court’s ruling could create unacceptable risks, hasten patient deaths and undermine the science-based clinical trial system.

Industry data show almost 90 percent of drugs that enter Phase I human clinical trials are subsequently abandoned because the formulations don’t work or turn out to be harmful.

It generally takes six or seven years to gather data and do laboratory testing from the time a pharmaceutical company discovers a promising molecule or compound until it can begin human clinical trials. It can then take another seven years to conduct three phases of testing for FDA review.

Partly in response to the court decision, however, the FDA in December proposed changes to its limited “compassionate use” policy that experts say will make it somewhat easier for patients to obtain experimental drugs when they can’t get into clinical trails.

The proposal would allow individual dying patients access to medications after Phase I testing if the preliminary evidence suggests possible effectiveness. Expanded access for large groups would require evidence of safety and effectiveness from Phase III clinical trial data.

Richard Samp of the Washington Legal Foundation, representing the Abigail Alliance, said the proposed policy falls far short of the access that is needed.

The FDA has permitted restricted availability to experimental therapies since the 1970s, with the policy often vague, left to the discretion of the agency and requiring numerous procedural hurdles.

Since its inception, the FDA said it has permitted more than 100,000 patients to receive investigational drugs outside the clinical trial setting. The policy was most extensively applied to patients with HIV and AIDS in the late 1980s.

Peter Jacobson of the University of Michigan Center for Law, Ethics and Health said the Abigail Alliance case presents a classic conflict between individual rights and the broader needs of society.

“Do I want to be the doctor telling a dying patient he has nothing to offer? No. Do I want to be the regulator saying you are not eligible for compassionate use of an experimental drug? No,” said Jacobson. “But if I am a regulator and I say you can have anything you want, how do I protect patient safety?”

Jacobson said he believes “the future of pharmaceutical regulation is at stake,” with affirmation of the court decision opening the floodgates to “snake oil” remedies, offering “false hopes” and unleashing dangerous, unproved medications on the public. He said the integrity of the scientific and regulatory processes must take precedence over individual demands, no matter how heartbreaking.

Patient groups have differing views, while the pharmaceutical industry has been taking a low profile and is generally reluctant to embrace expanded availability.

The National Organization for Rare Disorders supports expanded access, but no sooner than the completion of Phase II human trials, so that risks and potential benefits might be better understood.

“We are proponents of having expanded access to drugs that are in clinical trails. What we are not happy about is the pressure that has been put on the FDA to provide drugs to anyone who is in a very serious state and to give it to them when the drug is still in safety trials,” the organization’s Maria Hardin said.

Fran Visco, president of the National Breast Cancer Coalition, said experimental drugs should not be available outside of clinical trials.

“I understand the emotion that drives the Abigail Alliance, but this isn’t about emotion, it’s about saving as many lives as possible and not about getting as many drugs out as possible,” Visco said. “It’s about doing the right research and making sure we have patient protections in place and making drugs available that are truly helpful.”

Frank Marine of Vineland, N.J., whose fiancee Alita Randazzo died of colorectal cancer in 2002 after unsuccessfully trying to obtain an experimental drug, can’t understand such logic after watching the “terrible pain and suffering” of his loved one.

“If there is the slightest chance a drug will help somebody who is dying, they should get it,” Marine said. “Let them make the decision. It might help them, it might kill them, but let them make the decision.”

The pharmaceutical companies, the ones testing and having to supply the drugs for experimental use, are unenthusiastic because of the financial, legal and safety risks.

“In many cases, supply of such drugs is limited because companies may only produce enough for the clinical trials,” said Alan Goldhammer, a vice president of the Pharmaceutical Research and Manufacturers of America. “And there are ethical issues because experimental drugs need to be administered under informed consent.”