FDA Approves Wider Use of Test Drugs

In a historic change in the regulation of the nation’s pharmaceutical industry, the Food and Drug Administration on Thursday gave its approval to a regulation that will make experimental drugs significantly more available to seriously ill or dying patients.

The controversial new rule will allow people with “immediately life-threatening diseases” to decide for themselves either to take an experimental drug--with all its concomitant risks and side effects--or die untreated.

The rule authorizes the FDA commissioner to make available drugs that appear promising in clinical experiments, on a case-by-case basis. One prerequisite is that there be “no comparable or satisfactory alternative therapy” for the patient or the ailment in question.

The new regulation, to take effect in 30 days, was hailed by the pharmaceutical industry as being long overdue.

But it was harshly criticized by many leading biomedical researchers and physicians, including the president of the American Heart Assn. and the chief medical officer of the American Cancer Society. They said making unproven drugs broadly available unnecessarily endangers the well-being of already very ill people.

The new rule, spurred in part by the AIDS epidemic and the Reagan Administration’s commitment to deregulation, was published Thursday in the Federal Register, taking up 53 pages.

It applies only to drugs that are already undergoing traditional tests in humans for safety and efficacy. The regulation also specifies that such clinical experiments must continue even as the test drug is being made available.

Patients who will qualify for such drugs include those for whom there is “a reasonably likelihood that death will occur within a matter of months,” according to the regulation. Such patients also must demonstrate that they have exactly the form of the disease for which the test drug is undergoing clinical trials.

A Major Priority

In addition, physicians of such patients must demonstrate that they are qualified to supervise the administration of such experimental drugs.

Dr. Frank Young, in an interview, said that providing “desperately ill” patients with “breakthrough drugs” has been among his major priorities since he became FDA commissioner nearly three years ago.

Young noted that certain experimental drugs for several diseases have been available in the past, particularly in individual cases, and he added:

“The terrible disease AIDS and the desperate need for an effective treatment have focused public attention on this issue as never before.”

An FDA spokesman cited the recent experience with azidothymidine, or AZT, an experimental drug against acquired immune deficiency syndrome, as “sort of a pilot” for the new regulation.

AZT was being tested in about 200 AIDS patients when it appeared that its recipients were living longer than AIDS patients in the clinical trial who received only a placebo. At that point, even though the trial was far from over, the FDA allowed the drug’s manufacturer to make it available to all 6,000 AIDS patients who had the same kind of pneumonia as those who had responded to AZT in the tests.

Among the critics of the new rule is Alan C. Sartorelli, president of the American Assn. for Cancer Research, an organization composed chiefly of researchers who conduct trials of experimental cancer drugs.

Chaos Predicted

The rule would “create chaos,” he predicted. “There will be patients dying from the effects of the drugs because many (cancer) drugs are very toxic,” said Sartorelli, who directs the comprehensive cancer center at Yale University.

He said many community physicians who presumably would be administering test drugs may not be prepared to handle the severe side effects, such as kidney and liver failure, that such toxic agents can cause.

“I understand why terminally ill patients want to be able to decide what happens to their body,” Sartorelli said. “But in cancer, we are always concerned that patients not be given drugs that will harm more than they help.”

Another critic, Dr. Kenneth Shine, president of the American Heart Assn. and dean of the UCLA Medical School, said he is concerned that drug companies will be less motivated to go to the expense of conducting a series of trials to demonstrate a drug’s efficacy if, under the new regulation, they might be able to sell the drug to patients who are outside clinical trials.

According to the regulation, a drug company or other sponsors of a drug are allowed to charge patients to recover the costs of the drug, including its manufacture, the firm’s research and development costs and handling expenses.

Although these costs are presently covered for experimental medical devices, this is the first time this provision has been applied to experimental drugs.

Distribution of the drugs will be limited to licensed medical practitioners who are qualified by training and experience to use the drugs.

Shine said he is “sympathetic” to the plight of seriously ill patients, but added, “I still think the final chapter on whether it’s better to have early access to drugs that may (be unsafe or ineffective) has not yet been written.”

Dr. Arthur Holleb, chief medical officer of the American Cancer Society, said he favors the regulation only if it results in a greater number of patients entering clinical trials that are conducted by government and university medical centers.

“But if the patients were being used by inexperienced doctors in unsupervised trials of such drugs, I am opposed,” he said.

Holleb’s concerns were shared by Dr. Gregory Sarna, director of the Bowyer Oncology Clinic at UCLA’s comprehensive cancer center.

“There’s a danger to the patient if the drug is not proven and a danger to the nation’s research effort if it results in the dispersal of patients away from studies that could answer questions that need to be answered,” Sarna said.

Don Ralbovsky, a spokesman for the National Institutes of Health, the federal agency that funds drug trials for a variety of illnesses, said the agency has filed its comments on the regulation with the FDA but that there would be no immediate public comment.

Dr. Robert T. Levine, a Yale Medical School professor who has written a book on medical research ethics, said he regards the rule as “ethically acceptable if all the participants behave very carefully.”

List of Diseases

Levine added, “Some drugs are very tricky to use.”

The regulation’s preamble lists these life-threatening diseases whose victims might qualify for test drugs: advanced congestive heart failure, herpes simplex encephalitis, advanced and incurable cancer, very advanced emphysema, bacterial infection of the heart, brain hemorrhage, abnormal and uncontrollable heart beats and advanced AIDS.

Young said the new regulation will still require “safety and effectiveness, but a little less information.”

He said the agency “graded it with the risk that a person was facing.”

Urged by George Bush

In the past, the FDA has given such “compassionate use approval” to an average of 400 individual experimental drugs a year. But the number of beneficiaries typically has been relatively small. The new regulation is meant to apply to situations in which large numbers of people might benefit.

Some of the original proposals for the regulation were partly fueled by the Office of Management and Budget and were strongly encouraged by Vice President George Bush.

Young disagreed with critics who said the new rule places excessive authority in the hands of the FDA commissioner.

“The commissioner isn’t going to do it by himself,” Young said, adding that decisions on experimental drugs will essentially be made by committees within his agency.

“No commissioner is going to sit there and flip coins in the air and say ‘eenie, meenie, minie moe, this one yes, this one no,’ ” Young said.

He said the rule may stimulate the rapid development of many new drugs.

“If we can shave three years off the ability to bring breakthrough drugs, and there is no alternative therapy and those patients are going to die without it, then should the government be allowed to say no? We’ve got to be able to let the informed patient with the informed physician have a big share in the treatment,” Young said.

The new drug rule was praised by Dr. Robert K. Oldham, a former researcher for the National Cancer Institute who last year opened a Franklin, Tenn., company to provide cancer patients with experimental therapies for a fee.

Cancer Research Monopoly

He scoffed at the concern expressed by some academic researchers that private physicians may not be able to deal adequately with the possible side effects of highly toxic experimental cancer drugs.

“They say that liberalizing the regulations will cause increased toxicity, but what they are really worried about is their own monopoly over cancer research,” Oldham said.

Alan Goldhammer of the Industrial Biotechnology Assn., which represents the pharmaceutical and biotechnology industries, also hailed the new rule, calling it a “progressive measure.”

He added, “As these (experimental) therapies come out and are proven to be safe and efficacious, there needs to be a better mechanism of getting them into the hands of the people that need them.”

One issue that remains unresolved is whether health insurers will reimburse patients for the costs of such experimental drugs. At present, most do not reimburse for experimental therapies.

Elizabeth Mehren reported from Washington and Harry Nelson from Los Angeles.