The Drug Debate

By Jessica Gorman

The Drug Debate

Will earlier access to investigational therapies help patients or harm them?

By Jessica Gorman

When patients are faced with terminal cancer, it’s not uncommon for them to embark on a quest for drugs that are not yet approved by the U.S. Food and Drug Administration (FDA). There are different options for patients to try to obtain these drugs, including through clinical trials.

If trials aren’t available, patients can also inquire whether a drug manufacturer offers an expanded access program for a therapy or will make it available for single-patient use. In both cases, the company would provide the drug for free.

But are these programs enough? In the last couple of years, one patient advocacy organization, the Abigail Alliance for Better Access to Developmental Drugs, has launched an effort to broaden access to investigational drugs, through a lawsuit against the FDA and legislation, known as the Access Act, proposed in Congress in 2005.

These efforts have created a firestorm of debate. While nearly everyone sympathizes with the situation of a patient or family that lacks treatment options for a life-threatening cancer, many patient advocates and researchers say that the Abigail Alliance’s plans could potentially result in the use of harmful therapies that hasten death, upend the clinical trials process, and delay or kill potentially helpful new drugs for future generations of patients.

Abigail Alliance president Frank Burroughs calls those concerns “bogus.” Patients who are facing death have a right to investigational treatments, he says. Last May, a three-member panel of the U.S. Court of Appeals for the District of Columbia Circuit concurred, with one judge dissenting.

It’s a question that’s sure to garner more attention in coming months. In November 2006, the D.C. circuit court vacated the May decision, agreeing to an FDA request to have all 10 members of the court rehear the case.

Burroughs says he began to view the policies of the FDA as obstacles to expanded drug access shortly after the death of his daughter, Abigail, 21. Abigail, who had metastatic head and neck cancer, was unable to get the investigational drugs she sought.

According to Patty Delaney, the director of the FDA’s Cancer Liaison Program, it’s rare that the FDA would reject a request from a patient with no other options if a pharmaceutical company agreed to provide a drug, unless there is a safety issue. (Delaney and David Banks, also of the FDA, declined to speak specifically about the Abigail Alliance lawsuit because of the ongoing court case.) “But we cannot urge, cajole or otherwise encourage a drug company to make a drug available if they don’t want to do it,” Delaney says. “It’s inappropriate to do that.” Drug companies have many reasons for not offering expanded access, such as a drug’s cost or supply, she says.

The Abigail Alliance is calling on the FDA to create new tiers of drug approval. Tier 1 approval would let companies sell a drug as early as the end of the first phase of testing in people, known as phase I, if it shows significant signs of safety and effectiveness, says Burroughs.

The lawsuit and proposed legislation are “motivated mostly by frustration with the status quo,” says molecular biologist Robert Erwin, the director of the Marti Nelson Cancer Foundation, a nonprofit organization founded by Erwin’s wife, who died of breast cancer. “And I share all of those frustrations.”

However, the Abigail Alliance’s efforts are “misguided,” he says.

Though Erwin advocates that people first seek investigational drugs through clinical trials, he agrees with Burroughs that patients should be able to request a drug from a company when it’s in early testing—even, Erwin says, if it’s tested only in mice. But he strongly opposes the Abigail Alliance’s proposal to put what he calls an “FDA stamp” on these drugs or to let companies profit from them. FDA approval may mislead patients into believing more is known about a therapy than really is, Erwin says. He foresees a flood of unproven therapies on the market from overly optimistic drug researchers as well as from “charlatans and snake-oil salesmen.”

But tier 1 approval wouldn’t be a free-for-all, Burroughs insists. The Abigail Alliance itself has a perfect record of identifying and pushing for access to drugs in early testing that were later approved, he asserts.

Still, Mace Rothenberg, a medical oncologist at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., says the proposal to expand access to these drugs outside clinical trials makes him nervous. Many drugs that worked in phase I and phase II trials didn’t work in phase III, and giving these drugs to a terminally ill patient could hasten death, he says.

Banks, a pharmacist who is also trained in health policy, points out that a drug needs more than a promising mechanism of action for success. “What matters here is not how it works, but if it works—and what its risks and benefits are,” he says.

According to Rothenberg, the sale of investigational drugs may also cause fewer people to join clinical trials and delay the drugs’ full testing and approval. Incidents of side effects outside the structured setting of a clinical trial could derail a drug, he adds. Likewise, anecdotal reports of a drug’s benefits could encourage widespread use of a dangerous therapy, he says.

Burroughs argues that the Abigail Alliance is proposing a way to make potentially lifesaving drugs available while researchers continue to gather information about their effectiveness. Tier 1 approval for investigational drugs may also encourage insurance companies to pay for them, he says.

Rothenberg says it’s not realistic to believe that insurance companies would pay for the drugs, however, and without insurance coverage, the Abigail Alliance plan to let companies charge for investigational drugs would restrict them to a particular socioeconomic group.

But Burroughs says the most important question to ask is, “What do the patients think?” In his opinion, if patients are willing to accept a drug’s unknown risks, “we feel that’s their decision and their right [to have the drugs], in consultation with their doctor.”

Yet, Delaney, a two-time cancer survivor, suggests that families be sure to consider another question: Is a patient deciding to pursue a new drug for themselves, or because the family wants it?

The discussion of expanded access to these drugs is part of a healthy debate, says Erwin, even if he opposes the Abigail Alliance’s proposals.

“The goal of the Abigail Alliance and clinical researchers is not out of alignment,” Rothenberg notes. “The goal of both of our efforts is to improve and expedite the availability of effective drugs to treat cancer.”