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FDA Clarifies Rules for Getting Experimental Drugs
Drug makers and many patient advocates are pleased with the U.S. Food and Drug Administration's recent effort to shed light on when patients can get experimental drugs outside a clinical trial. But the most vocal critics of current policy are far from mollified by the new effort.
More than 10 years after Congress directed the FDA to establish a way to allow seriously ill patients access to promising—but unapproved—drugs, the agency is in the final stages of setting out rules to formalize what has until now been an informal and not always transparent system for granting access outside clinical trials. In recent years, advocates of more access have gone as far as suing for more control.
The policy represents the FDA's attempt to strike a delicate balance between the wishes of individuals and the needs of society. Through that mechanism, more than 100,000 patients have already received experimental drugs, the agency estimates.
"One goal is to enable many more patients who lack satisfactory alternatives to have access to unapproved medicines while balancing the need for safeguarding the individual patient," FDA Commissioner Andrew von Eschenbach, M.D., said in a statement. "Another equally important goal is to ensure the continued integrity of the scientific process that brings safe and effective drugs to the market."
Those goals are set out in the proposed rule, which was published on Dec. 14. The comment period ended March 14. Under the guidelines, there are three ways that patients can get access to unapproved drugs. Individual patients, with the help of a physician or other advocate, can make a request directly to the FDA to gain access to an experimental drug. A large pool of patients who do not qualify to participate in the clinical trials can get access if the drug company files a special Investigational New Drug application, known as a treatment IND, which requires less red tape than an individual request; this type also requires more data tracking. A midsized group, between 10 and 100 patients, can qualify through a middle ground that means less work for patients than an individual application and fewer data requirements for companies.
The rule is a welcome clarification of existing FDA policy, said Sara Radcliffe, vice president for science and regulatory affairs at the Biotechnology Industry Organization in Washington, D.C., which made no official comment on the rule.
"I can’t say that this will make our companies more willing to engage in this, because they are already very willing to work with the FDA to make it happen. It may streamline the process and help them understand what they need to do and make it go a little faster," she said.
Having a written policy should also help physicians in their role as advocates for patients wanting access to experimental drugs, Radcliffe said.
"If [physicians] are faced with this situation, this rule will give them a lot of guidance about the kinds of factors that FDA considers in making decisions," she said.
The FDA does a pretty good job at balancing access to drugs and public safety under the existing policy being formalized with this rule, said Robert Erwin, president and founder of the Marti Nelson Cancer Foundation, a nonprofit organization that helps cancer patients apply for experimental drugs through compassionate-access programs.
"For the most part, the FDA is not an obstacle to expanded access. If a company is willing to provide it and a patient asks for it, it's very rare that the agency stands in their way," Erwin said. He submitted brief comments to the FDA in support of the proposed rule.
Going Around the FDA
However, not everyone agrees that FDA staff should be the ones making decisions about access to cancer drugs.
Once adequately informed of the risks inherent to experimental treatments, patients should have access to those drugs without interference from regulators, according to members of the Abigail Alliance, a group of cancer patients and their families.
In an ongoing lawsuit against FDA brought on behalf of the alliance, lawyers with the Washington Legal Foundation have argued that terminally ill patients have a constitutional right to live by seeking access to all available treatment options. They argue that the FDA has little reason to withhold promising drugs for safety reasons when the patients’ illnesses already place them in mortal danger. This position does not imply that terminally ill patients can demand treatment from unwilling doctors and drug companies but rather that the FDA should not block treatment by willing parties without providing a compelling reason to do so.
"What's at stake really is how good of a reason should the FDA have to give in order to interfere with a patient's own judgment and their treating physician's own judgment about the best course of treatment," Scott Ballenger, a partner in the Washington office of Latham & Watkins, said at a recent colloquium sponsored by the Food and Drug Law Institute in Washington, D.C.
"In every other life-threatening situation, we let people do absolutely extraordinary things. We let people, in a good-faith attempt to save their life, kill another human being," said Ballenger, who is providing his pro bono assistance in the case.
That standard sets a dangerous precedent, Erwin said. "That to me would be asking the government to sanction the sale of toxic placebos. There are just so many drugs that don’t make it through phase I, phase II, or even phase III, that to say those should be sold to people looking for cancer treatment is just irresponsible," he said.
There is also concern within FDA and with physicians who run clinical trials that open access to experimental therapies could severely hinder the agency's ability to rigorously study drugs in randomized clinical trials, a worry that has bred tension among patient groups, said Scott Gottlieb, M.D., who until recently served as the FDA's deputy commissioner for policy.
"When you are talking about cancer, you’re talking about a very bifurcated community. ...If you are diagnosed with a cancer with a 20% cure rate, you are looking for experimental treatments, new options, right from the get-go. If you’re diagnosed with something with an 80% cure rate, you’re looking for more data," said Gottlieb, now a resident scholar at the American Enterprise Institute, a conservative think tank in Washington, D.C.
Old Obstacles
Even if the Abigail Alliance prevails in its lawsuit, forcing the FDA to stand aside, patients with cancer and other serious conditions may not get ready access to experimental treatments, experts warned.
"If the drug companies don’t provide the experimental drug, even if they have permission to do so, all of this discussion is going to come to naught," said Mark Gately, a partner with the law firm Hogan & Hartson.
Even within the confines of a clinical trial, drug companies risk being sued if something goes wrong with an experimental drug. That risk is even greater outside that controlled setting, Gately said at the colloquium.
Cost is another obstacle that may keep drug companies from participating in expanded-access efforts. With the expanded-access rule, the FDA released a proposal that would limit how much drug companies can charge for experimental therapies to manufacturing costs. But that doesn’t mean the drugs will come cheap. Since they are often produced in relatively small quantities, the cost of additional drugs is likely to still be substantial.
"If patients are allowed to have access to experimental therapies for treatment purposes for terminal illnesses, how will they be able to afford these medications? That's the one question that we really need to answer," said Frank Palumbo, Ph.D., director of the center for drugs and public policy at the University of Maryland School of Pharmacy.
Many cancer regimens cost tens of thousands of dollars, and health insurers and other payers are often hesitant to pay for any treatments that are unproven, he said.
Although drug companies most often donate experimental drugs on a compassionate-use basis, patient advocates are wary of proposals to create financial incentives that would encourage companies to make their experimental agents available, Erwin said.
"When you introduce the profit motive into this, you are encouraging a lot of people to cut corners and to come out of the woodwork with things that are only designed to make a short-term profit," he said.
Coinciding with the expanded-access rule, FDA published proposed regulations that would restrict companies to charging only what it costs them to make experimental drugs.
Together, the rules provide much-needed clarification, but they don’t really advance the ball too much for allowing earlier access for patients not in a clinical trial, Gottlieb said. However, other factors, such as reforms under the Critical Path Initiative, may soon come into play that may change how and when seriously ill patients get access to experimental drugs.
"There are opportunities to rethink the ways in which we conduct clinical trials in this country that would enable both the rigorous collection of important clinical data and facilitate more widespread access," he said.
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