Ease AIDS Drug Rules, Health Chief Urges

SAN FRANCISCO —  Bowing to what he termed “constructive pressure” from AIDS advocacy groups, federal AIDS chief Anthony S. Fauci proposed Friday that a “parallel track” of AIDS research be established to allow AIDS patients who are otherwise ineligible for controlled clinical trials to gain access to experimental AIDS drugs.

“My commitment to carefully designed, controlled clinical trials for AIDS has not changed,” said Fauci, speaking here at a medical forum on early intervention against the human immunodeficiency virus (HIV). “Such trials are absolutely essential if we are going to get the answers needed by physicians who are treating patients.

“At the same time,” he added, “we have to be creative and flexible so we can provide increased access to promising drugs to patients who cannot participate in clinical trials.” Once a drug has proven itself to be safe in early toxicity trials, Fauci continued, “we have got to rethink the rigidity with which we exclude people.”

Major Philosophical Change

Fauci’s proposal represents a major philosophical change for the National Institutes of Health, where Fauci is head of AIDS activities, and it illustrates the way in which AIDS is revamping the way scientific research is conducted. His announcement drew a sustained round of applause from the 1,000 people--many of them HIV-infected--attending the medical forum during HIV Treatment Awareness Week.

Some have argued that there is an inherent conflict between the demands of conventional science, which has traditionally required carefully controlled studies of drugs before drawing scientific conclusions, and patient demands for potentially promising therapies.

“Collecting data from the (patients enrolled in) the parallel track” enhances scientists’ ability to come up with definitive answers on the usefulness of experimental compounds, said Fauci, who is also director of the National Institute of Allergy and Infectious Diseases (NIAID). And if this system works well with AIDS, it will likely be extended to other life-threatening illnesses, such as cancer.

Phase 1 Study

Typically, when experimental drugs are tested in humans, they are first examined only for safety, to be sure there is no toxicity associated with taking the drug. This is known as a Phase 1 study.

Phase 2 studies, which attempt to determine if a drug is effective, are usually highly structured trials that involve a control group whose participants receive either a worthless placebo or another drug. There are only a limited number of spaces for participants in these trials.

The new proposal would involve the Phase 2 stage, in which “parallel tracks” would be far less structured and would probably not involve a control arm, Fauci said. Participants would be those who were not eligible for the more structured trials.

Existing Phase 2 trials have rigid criteria for enrolling patients. They must have precise levels of immune deficiency, for example, and in certain cases must not have tried other drugs.

Promising Activity

Fauci said one candidate for parallel track testing status is the antiviral compound DDI, a compound made by Bristol-Myers Co. that has shown promising antiviral activity and little toxicity in Phase 1 trials at the National Cancer Institute.

“I think DDI should be very seriously considered in this framework and, in fact, we are discussing it with the drug company,” he said.

Fauci stressed that his proposal “cannot happen by fiat. It is a concept that is going to have to involve drug companies, investigators, the Food and Drug Administration.” But he expressed confidence that the FDA will sanction the action and that some drug companies and scientific investigators will cooperate.

FDA Administrator Dr. Frank Young said in an interview that he has discussed the proposal with Fauci and supports the new initiative but cautioned that “it has to be looked at on a drug-by-drug basis.” He said opening up Phase 2 trials to more participants would “make Phase 1 toxicity trials more important.”

“The answer may be ‘no’ for this drug, and ‘yes’ for another,” Fauci said at a press conference after his presentation. And, in any case, I am not talking about wide availability involving thousands and thousands of people.”

Behind-Scenes Lobbying

Fauci unveiled his new initiative after months of behind-the-scenes lobbying by Martin Delaney, co-founder of Project Inform, a San Francisco-based advocacy group and treatment-information clearinghouse, and by members of the New York chapter of the AIDS Coalition to Unleash Power (ACT UP).

Fauci said that he met with members of ACT UP for nearly three hours this week in his Bethesda, Md., office to hash out details of the proposal.

Delaney was quick to applaud Fauci’s announcement. “Patients have been saying for a long time that they are willing to take additional risks in return for accelerated drug development,” he said in an interview.

Indeed, he added, referring to the growing underground of unlicensed medicines, “they are doing it anyway. This will let them take their risks in a controlled setting while accruing scientific knowledge.”

Last winter, NIAID announced another program that will expand AIDS research to include local, community-based physicians, in addition to those who now conduct the traditional studies at large academic medical centers.

Reaction to the program was mixed. “It’s a very interesting approach, and where is the money going to come from?” asked Jeff Levi, executive director of the National Gay and Lesbian Task Force. “Who is going to pay for the drugs and associated care? Will it be NIH? The drug companies? Third-party payers? Or is this going to be of value only to those wealthy enough to pay for the drugs?”

Dr. Robert T. Schooley, an AIDS specialist at Massachusetts General Hospital, said he was concerned that potential toxicity “might be missed” in Phase 1 studies, “as has happened with several AIDS drugs.”

But Delaney was successful in persuading Fauci that such concerns had to be balanced against the lives lost by delays in drug development. “People talk about the possibility of losing lives due to toxicity, but nobody is counting the lives lost due to delays in drug development,” Delaney said.

Victor F. Zonana reported from San Francisco and Marlene Cimons reported from Washington.