FDA Probes Underground Testing of AIDS Drug

SAN FRANCISCO —  The U.S. Food and Drug Administration said Tuesday it has launched an investigation into an underground AIDS drug trial after reports that one patient in the study had died and others had suffered serious adverse reactions.

The trial, an audacious challenge to the federal regulatory system, was designed to quickly test the safety and efficacy of a highly touted Chinese drug known as Compound Q.

The experiment was undertaken without FDA sanction or approval by Martin Delaney, co-director of Project Inform, an advocacy and treatment information group, and is being conducted by doctors in San Francisco, New York and Los Angeles using drugs imported into the United States from China.

‘Scale and Nature’

In announcing the probe, the FDA said it will look into the “scale and nature” of the Project Inform operation, the experiment’s safety procedures and “the exact circumstances surrounding the death and other adverse reactions.”

“Questions also remain about the exact composition of the product and whether it was illegally imported into the country,” the agency added.

Boyd Stephens, San Francisco’s chief medical examiner, said Tuesday that he had declined to perform an autopsy on 45-year-old Robert Parr, the patient in the unauthorized clinical trial who died Saturday.

“We concluded that the death was likely the result of the patient’s underlying condition, AIDS” he said.

Those conducting the experiment insist that they have been operating within the law because FDA regulations allow, under certain conditions, treatments with unproven drugs obtained from overseas.

But, former FDA Commissioner Dr. Jere E. Goyan, currently dean of UC San Francisco’s School of Pharmacy and himself an advocate of regulatory reform, said, “It seems like a straight-forward challenge of the regulatory system to me.

“They are depending on a very frail argument--that individual patients can bring in drugs for individual use,” Goyan added. “My guess is that the agency’s lawyers could easily destroy the argument, if they wanted to.”

Compound Q is a Chinese drug made from the root tubers of a cucumber plant and has been used in China to induce abortions and for cancer treatments since the Third Century. Some researchers say the drug selectively kills certain cells infected with the human immunodeficiency virus that causes AIDS.

Meanwhile, several medical ethicists said they understood the frustration that might drive physicians to want to circumvent the FDA. But they said the experiment could backfire, hurting not only patients but the future of Compound Q and other experimental drugs.

“This is a logical outgrowth of what we have seen during the epidemic,” said Dr. Marcus Conant of San Francisco, a prominent AIDS doctor who declined an invitation to participate in the trial. “These patients are young and well-educated and are not going to sit around while institutions like the FDA fail to save them.”

Dr. Robert J. Levine, a professor of medicine at Yale University who specializes in the ethics of clinical trials, said the unsanctioned trial could actually end up slowing down the process of making Compound Q widely available to patients.

Have Power

“The FDA could say, ‘We are not going to review these data because you violated our regulations,’ ” Levine said. “They also have the power to approve it. But I think people at the FDA would have some anxieties about setting such a precedent.”

George Annas, a professor of health law at Boston University School of Medicine, called the trial “more a political action than a scientific action.” Annas and others said the study circumvents not only the FDA but also long-established rules for protecting human subjects.

For example, federal and state rules governing university-based and federally funded trials require evidence that a drug’s potential benefits outweigh its potential risks. Annas noted that the rebel researchers have not done preliminary safety studies that would answer that question.

“You’re dealing with a drug that’s potentially dangerous,” Annas said. “Until you get more information on the toxicity level, I think it’s premature to go ahead and give it in therapeutic doses to human beings.”

Accepted research rules also require proof that patients in trials have given their “informed consent.” Annas said it would be impossible to get informed consent in the absence of information about risks and benefits that would be gleaned from preliminary work.

“It seems to me that starting a trial without a clear understanding of a drug’s toxicity is both professionally and morally irresponsible,” added Ronald Bayer, an ethicist and associate professor at Columbia University’s School of Public Health.

Trial Defended

But supporters of the unauthorized drug testing program, noting that AIDS is now claiming about 100 Americans a day, staunchly and emotionally defended the trial.

“How dare the government and the ethicists stand in our way with yesterday’s morality?” demanded New York playwright and AIDS activist Larry Kramer, who cited anecdotal reports of great improvements in experimental subjects.

“The world must know that we are capable of running our own studies, and that the system is murderously slow, and that we cannot wait,” Kramer added.

“I understand the desperate need,” said Albert Jonsen, a professor of ethics in medicine at the University of Washington. “But it’s precisely the desperate need that gets us into trouble. . . . To get a drug out that is primarily understood on the basis of rumor rather than the rigorous evaluation the system calls for is, I think, a mistake.”

Dr. Larry Waites, a San Francisco physician participating in the trial, argued Tuesday that there was a “moral obligation” to set up the trial. With Compound Q available on the black market, AIDS patients would be risking their lives to take it unsupervised, Waites said.

“We were faced with a very explosive situation,” Waites said Tuesday. “We knew that hundreds of thousands of doses of this drug were going to be imported soon. We knew that people could do themselves great harm taking the drug without supervision.”

As for the patient who died, Waites said Parr went into a coma in reaction to the drug. Waites said the patient was “recovering nicely” but then vomited in his sleep and suffocated.

Waites called the patient’s death “a complication, certainly, of his recovering from his coma.” But he said the researchers do not consider the death a side effect of the drug.

Among those monitoring the experiment was a representative of the American Foundation for AIDS Research’s directory of experimental treatments.

“When it became clear that a (Compound Q) treatment program was in motion, we moved rapidly to get a reporter on the scene to capture as much hard data as possible,” said Mitchell Speer, editor of the directory.

“As we see it, there just isn’t enough data currently available to draw any solid conclusions about the usefulness of this agent,” he added.

Waites said the Compound Q trial is being conducted largely by practicing physicians under the leadership of two San Francisco immunologists, Dr. Alan S. Levin and Dr. Vera Byers. Waites said Byers has worked extensively with another drug related to Compound Q.

On the basis of Byers’ experience, and reports from China, Waites said the group was able to predict and treat the side effects of Compound Q injections--mostly “aches and pains” in the 72 hours after the weekly intravenous injection.

Zonana reported from San Francisco and Scott from Los Angeles.