FDA Watch: Unequal Treatments


Most people wouldn't mind a trip to the Bahamas just before Christmas. Charles Greene did. Number one on his sight-seeing list was a local establishment called the Apothecary, and the souvenir he was hoping to bring home was no mere trinket. It was a supply of pills for his ailing father. U.S. Food and Drug Administration policy had forced this otherwise law-abiding mathematician to become a drug smuggler, and he was very worried about getting caught.

Greene's 84-year-old father had Alzheimer's disease, a fatal nerve disorder that causes loss of memory and muscle function. One physician, moved by the sight of the Harvard-educated chemist unable even to dress himself or swallow solid food, suggested a promising experimental Alzheimer's drug known as THA. Unfortunately, the FDA had imposed an "import alert" on the drug in December 1988.

The agency claimed that THA "is known to be a potent hepatotoxin" (causing liver damage), despite data from an international array of doctors arguing that the drug's benefits far outweigh any risk. So Greene had to go abroad at great cost and inconvenience in search of THA: to the Bahamas, to Canada, to Belgium. Greene's father has since died, but hundreds, perhaps thousands, of other Americans with relatives suffering from Alzheimer's continue to risk arrest and prosecution for a chance to help their loved ones.

AIDS patients have it a little easier. Dozens of "buyers' clubs" throughout the United States routinely import large quantities of experimental drugs, such as Peptide T and DDC, for sale to AIDS patients. The activities of these organizations are clearly illegal under FDA regulations, which allow patients to import only small quantities of unapproved drugs for personal use. Yet the agency tolerates the buyers' clubs and equivocates when asked about their legal status.

In July 1991, during the same week that an FDA advisory committee recommended that the agency continue to keep THA off the U.S. market, another advisory committee recommended approval of DDI, an AIDS drug officially blamed for at least six deaths. That week, AIDS activists marched in front of the FDA building in Rockville, Maryland. No one marched for Alzheimer's patients.

In recent years, patients seeking access to experimental drugs have noted a double standard in FDA policy—a lenient approach for AIDS, a stricter one for other fatal illnesses. Under pressure from AIDS activists, the agency has bent and modified its rules, winking at practices that violate regulations and expediting approval of experimental drugs.

On the PBS series TechnoPolitics last May, FDA chief David Kessler explained: "The AIDS community has taught the agency about the importance of getting drugs out there as soon as there is reason to believe that a drug works and that it's safe, and unnecessary delays are intolerable when one's dealing with life-threatening diseases." In fact, the FDA seems to have learned quite a different lesson: The squeaky wheel gets the grease.

"Our older people are really getting a raw deal," says Jim Driscoll, an AIDS activist and president of the PATH Foundation. "They're treated like criminals because they don't have the ability at this point to bring political pressure on this particular issue, whereas AIDS patients do have the political power. They are younger, they can take to the streets, and they are treated much, much better than people with Alzheimer's or cancer."

Says Michael Fumento, a former AIDS analyst for the U.S. Commission on Civil Rights, "You don't see too many Alzheimer's quilts. You don't have Alzheimer's people chaining themselves to the FDA's doors."

On December 13 a group of Alzheimer's patients challenged the FDA's double standard in federal court. They filed a class-action lawsuit against the agency, seeking approval of THA for general use. The lawsuit notes that, unlike the nation's 4 million Alzheimer's patients, the 100,000 AIDS patients already have an approved drug (AZT). It concludes that "without question, the record demonstrates gross inconsistency in the FDA's approval and non-approval of these respective drugs." The suit charges that the FDA's treatment of THA violates the Administrative Procedures Act as well as the rights to privacy and freedom of choice in health care protected by the Ninth and 14th Amendments.

The lawsuit may have had some effect already: In February the FDA began allowing 3,000 patients access to THA in order to collect more data on the drug's efficacy. But the plaintiffs aren't satisfied: What about the other 4 million Alzheimer's patients?

It was a November 1986 paper by Dr. William Summers in The New England Journal of Medicine that first documented the success of THA in slowing the progressive loss of brain cells controlling memory and reasoning that is an early sign of Alzheimer's. Ostensibly to confirm Summers's data, in June 1987 the FDA launched a study of THA. Saul Kent, president of the Florida-based Life Extension Foundation, which is bankrolling the THA lawsuit, charges that the FDA's study was in fact "a deliberate campaign to sabotage the drug." FDA officials did not heed Summers's caution that liver damage was a potential, but reversible, side effect, and they did not allow researchers to administer the memory-enhancing nutrient lecithin along with THA, as Summers had.

In fact, Summers declined an invitation to participate in the study because, he said, the FDA had no intention of duplicating his work. But doctors in Canada, Sweden, and Britain were doing just that. Their findings, reported in the British medical journal The Lancet and elsewhere, supported Summers's conclusions.

An FDA advisory committee on THA finally met in March 1991. Researchers from the drug's sponsoring company, Warner-Lambert, presented evidence that THA was effective for more than 40 percent of the patients in the study. Nonetheless, at a second meeting in July, the committee decided the study "had failed to show sufficient clinical effect to warrant approval of THA" and expressed concern about possible liver damage.

Summers and his colleagues protested that the government-organized study hadn't administered lecithin along with THA. In The Lancet, they disputed the charges of severe liver damage: "THA has been said to be severely hepatotoxic. We disagree. Although 8 (18%) of the 45 patients had any abnormality in liver function tests, only 2 were removed from the study for this reason, and in those exposed to THA for 18 months on average there was no trend towards cumulative toxicity." Dr. William Maddray, a hepatotoxicology specialist, had testified at the FDA's hearings that, when monitored through routine blood tests, a patient taking THA was "highly unlikely" to suffer permanent damage.

Meanwhile, relatives of Alzheimer's patients who participated in the study insisted they had seen improvements in the conditions of their spouses and parents. Last April The Wall Street Journal printed messages to the FDA from some of them. One man wrote: "Get off your butt! Get on the fast track and release THA for Alzheimer's patients as you released AZT for AIDS. THA gave my wife three fairly good years before Alzheimer's gained the upper hand and I finally had to place her in a nursing home in July 1990. People with Alzheimer's are sentenced and on death row. Help them, FDA, while medical science searches for a cure."

A woman wrote: "THA did not restore [my husband] to normalcy, but he no longer walked five feet behind me, could cut his own food, feed himself, recognize me, and play limited golf. He again had hope and would smile and laugh and try! The FDA allowed us to import THA for our own use. After several months, it rescinded the permission. Under the guise of protecting us, the FDA is making a criminal of me."

The FDA ignored Summers's objections and dismissed the claims of family members as "anecdotal." At the agency hearings on THA, Kessler repeatedly asserted: "Above all, we must maintain our standards."

Those standards can be flexible, however. In 1989 the FDA began investigating Project Inform, an AIDS advocacy group in San Francisco that was conducting a secret trial of the experimental, highly toxic AIDS drug Compound Q, which the organization was importing from China. (The drug is derived from the root of a cucumber plant the Chinese have used for centuries to induce abortions and treat cancer.)

Two patients participating in the secret project had died, possibly from the drug's high toxicity, and several others had experienced seizures or severe dementia. There were rumors that the FDA might bring charges against the renegade researchers.

But by March 1990 the agency had reversed course, not only downplaying Compound Q's serious side effects but giving the researchers its blessing to continue with their work. Never before had the FDA given a community organization, rather than a medical group, full control over research involving an unapproved drug.

Since then dozens of buyers' clubs for experimental AIDS drugs have sprung up around the country, in flagrant violation of the FDA's rule that only personal quantities of unapproved drugs may be imported. The FDA has proven "completely unwilling" to crack down on their illegal activities, says Steven Fowkes, president of Direct Action for Treatment Access in Palo Alto, California. He says the agency has a "two-tiered enforcement system, because the FDA knowingly allows buyers' clubs to sell drugs illegally, and yet it's not OK for other people to sell drugs illegally."

Asked whether buyers' clubs are illegal, FDA spokesman Don McLearn is noncommittal: "We are dealing with that now. In fact, we've gone around to buyers' clubs and discussed with them where lines may be drawn. We have explained to them that if they are going over that line we may have to take some legal action."

In turning to buyers' clubs, AIDS patients take responsibility for weighing the risks and benefits of using experimental drugs. Alzheimer's patients and their families argue that they, too, should be free to choose—between the oblivion of Alzheimer's disease and the possibility of reversible liver damage.

Most Americans seem to agree. In a nationwide survey conducted last fall by the Wirthlin Group, nearly 80 percent of respondents said an individual should have the right to use an unapproved drug for treatment of an incurable illness.

"It is immoral for the FDA to deny access to drugs for life-threatening illnesses for which there is no medical treatment," says Fowkes. Fumento argues that "the information is the most important thing" in the choice to try an experimental drug. "If somebody wants to experiment with their own life, that's fine," he says. "And if a doctor, with full and informed consent, to a degree wants to experiment with somebody else's life, that's fine too."

The problem, Fumento says, is that a regulator's interests differ from those of the people he supposedly serves. "The bureaucrat's view is very simple," he says. "If I, as a bureaucrat, prevent a drug from going into use, and the prevention of that drug results in 100,000 deaths, no one will ever stick that on me. But on the other hand, God help me if I approve something prematurely and one person dies from it. Then I'm out of a job; then my name is mud throughout history."

George Rehnquist, a board member of Families for Alzheimer's Rights, is unmoved by the FDA's claim that it is only protecting the public: "The government should not be playing God with our loved ones."

Elizabeth Larson is a REASON researcher-reporter.