In the wake of the Vioxx fiasco, the Food and Drug Administration has come under repeated attacks for failing to protect the public from unsafe drugs. An Institute of Medicine report released last fall blamed the agency''s internal culture, which emphasizes faster new drug approvals over monitoring the safety of drugs already on the market. Safety advocates on Capitol Hill will have their say in numerous public hearings later this year.
Given these heightened concerns about safety, you''d think the FDA would be extremely wary of opening the door to greater use of unproven drugs. But thatâ€™s precisely what the agency proposed in mid-December, largely in response to court rulings in a suit filed by the Abigail Alliance, a patient advocacy organization formed in 2001 by Virginian Frank Burroughs shortly after his 21-year-old daughter died of head and neck cancer.
Last May, a three-judge panel in the U.S. Court of Appeals for the District of Columbia ruled that terminally ill patients like Burroughs'' daughter have a constitutional right to unapproved drugs as long as the potential benefit exceeds the risk. As a practical matter, the ruling opened the door for any critically ill patient to gain access to any drug that had passed the minimal testing characteristic of small-scale Phase I safety trials.
The FDA immediately appealed the ruling, after two attorneys wrote in the New England Journal of Medicine that it threatens "the ability of the FDA to protect public health." If the full appeals court refuses to overturn the ruling, the agency will probably appeal to the Supreme Court.
Given the libertarian leanings of the Bush administration''s most recent appointments to the high court, it''s not surprising that the agency has moved to head off the suit by widening its existing expanded access rules, which are sometimes called compassionate use rules. Community oncologists have a lot riding on the final disposition of this proposed regulation because it is going to increase pressure to find experimental medicines for dying patients, even if they are not enrolled in clinical trials.
The FDA first released expanded access rules in 1987 in the midst of the HIV/AIDS crisis. Dying patients demanded access to the handful of experimental drugs. After numerous demonstrations by militants at FDA headquarters, the agency complied.
However, those regulations upheld the primacy of the scientific process over the patient''s right to experiment on themselves. The scientific evidence "taken as a whole" had to suggest the drug would work, and the company had to be actively seeking FDA approval through controlled clinical trials. The idea was to extend treatment to dying patients who might have been excluded from Phase III trials because they were too sick or in other ways didn''t meet the trial''s inclusion criteria.
The FDA estimates that in the succeeding two decades, more than 100,000 patients received investigational drugs under expanded access programs. But most were run through company programs under FDA-approved protocols. The rules did allow for individual patients and their physicians to seek experimental drugs, but very few did, largely because no criteria were spelled out for treating physicians.
The proposed rule opens the door for community physicians. They will be able to obtain experimental drugs for their patients as long as they tell the FDA that the risk from the experimental drug is not greater than the risk from the disease being treated. They also must certify that the patient can''t get the drug from a company program like an ongoing clinical trial. At the end of the treatment, the physician must provide a written summary of the results, including any adverse effects. The rules allow both physicians and drug companies to get reimbursed for these "treatments."
Note what''s missing from the criteria. There is no mention of the "weight of scientific evidence" to justify prescribing the drug. There''s also no requirement that these individual patients be organized into a systematic clinical trial, although the rule states the FDA "may ask the sponsor to submit an Investigative New Drug application or protocol for the use."
There are huge risks in this approach. For drug companies, it''s going to make it much more difficult to recruit patients for legitimate clinical trials. Moreover, the medical literature will undoubtedly become flooded with case studies and small-scale observational trials of dubious quality or predictive power.
Doctors will come under enormous pressure from sub-cults of dying patients who exchange hot tips over the Internet about the latest "miracle" drugs. Those who are leery of participating may face lawsuits from surviving family members or dying patients who feel they were denied information about all their options. Even if doctors properly caution patients about how little is known about the drug, they may be accused of malpractice if the drug turns out to be dangerous.
The biggest risk of all may be to medical science. Most cancer drugs fail. It''s hard not to sympathize with patients who want to fight for their lives with every available weapon. But that doesn''t give them the right to drag down evidence-based medicine with them.
Merrill Goozner is a contributing editor to Healthcare Journal of Northern California.
--By Merrill Goozner