Case of The Unexplained Deaths

By ANDREW PURVIS

AIDS activists have been vocal in urging the Food and Drug Administration to relax its standards and authorize for general use several experimental drugs that appear to help fight the disease. Even though many medical experts worry about the dangers of releasing relatively untested drugs to a broader population, the FDA made a controversial decision last year to allow wide distribution of certain drugs that are still in the testing phase. Among the first was DDI, or dideoxyinosine, an unproven medicine dubbed by its enthusiasts "AZT without tears." The reference is to the most commonly used anti-AIDS drug, which can produce distressing side effects.

Last week a report from Bristol-Myers Squibb, the manufacturers of DDI, suggested that the skeptics may have been right. The report disclosed that of 8,000 patients who had been taking DDI for seven months under the FDA's "expanded access" program, 290 died. That was ten times the death rate found in Bristol-Myers' own controlled clinical trial, in which 700 patients have received DDI. The report raised concerns not only about the safety of the drug but also about the FDA's new liberalization program.

The actual cause of the 290 deaths is not yet known. Many researchers feel the most likely explanation is a simple one: the 8,000 people receiving the drug under the alternate program were sicker than those in the clinical trials. To be eligible for DDI in the expanded tests, patients must be suffering from advanced AIDS and must be resistant to AZT. "For these people, DDI is a last-ditch effort," says Dr. Bernard Bihari of the Community Reseach Initiative, a clinic offering the drug to AIDS sufferers in New York City. Dr. Anthony Fauci of the National Institutes of Health observes that the death rate was much lower than that found in the early trials of AZT. But the report does raise "a red flag," adds Fauci, obliging either Bristol-Myers or the Government to investigate the affair.

Other experts feel the disclosures underscore serious problems with the expanded-access program. In traditional clinical trials, a small group of doctors closely monitors every patient. But in the expanded-access program, hundreds of doctors may administer the drug nationwide without consistently exchanging information. As a result, many participating physicians may not hear about significant side effects. "The shock to me was that I had to learn about these deaths from the newspaper," says Dr. Jeffrey Laurence, an AIDS researcher at Cornell University Medical College. He calls for a centralized monitoring system for doctors who are administering DDI.

Still others argue that the entire program is flawed. Dr. Thomas Chalmers of the Harvard School of Public Health calls the DDI death rates "a disgrace." He believes all 8,000 people should have been enrolled in a fully controlled clinical trial. But most doctors feel the program will continue. If the restrictions were tightened, AIDS sufferers would probably find other ways to get experimental drugs. At the very least, the new plan is offering one last chance to thousands of patients with little other hope.