The deaths of five of 15 participants in a catastrophic 1993 hepatitis B drug study on the experimental drug FIAU were unavoidable, the Institute of Medicine said in a report released Thursday.
"An elaborate system is in place to protect patients during clinical trials and serious harm is rare," said Dr. Morton Swartz, chairman of the institute panel that conducted the review. "Findings from previous animal and human tests . . . didn't expose this drug's life-threatening side effects.
"The researchers did everything they could to protect the lives of these patients," added Swartz, professor of medicine at Harvard University Medical School and emeritus chief of the infectious diseases unit of Massachusetts General Hospital. But he acknowledged: "That's cold comfort to the families of those who died."
Hepatitis B, which is caused by a virus, infects about 300,000 Americans annually and is a serious problem worldwide, affecting an estimated 300 million people.
The vast majority of those who become infected clear the virus and recover on their own. A small percentage, however, remain chronically infected and are at high risk of developing serious liver disease years later, including cirrhosis (scarring), liver failure and liver cancer. About 4,000 to 5,000 Americans die every year from the chronic effects.
The only currently approved treatment for chronic HBV infection is alpha interferon, which can produce severe side effects and is only effective in 25% to 40% of patients.
FIAU, or fialuridine, was an extremely promising compound that appeared in early tests to be highly effective against the hepatitis B virus and researchers were excited about its potential.
However, in June, 1993, 13 weeks into the planned six-month study, one patient suddenly became sick and was hospitalized with liver failure. Although the federally run trial was immediately halted and all the participants were told to stop taking the drug, six more individuals became gravely ill and five of the seven died.
The independent Institute of Medicine report said researchers were slow to tie FIAU to liver damage for several reasons. For example, although some patients who later died experienced a rise in liver enzymes, a possible sign of liver damage, such an increase is commonly seen just before the body rids itself of the virus.
Also, patients in earlier trials of the drug developed serious health problems weeks or months after stopping the drug, leading researchers to believe that the conditions were attributable to other factors.
Matthew Myers, an attorney who represents the families of two of the patients who died and a third who became ill, said: "The report can only be described as a whitewash by the scientific community. The Institute of Medicine relied entirely on what the researchers and the sponsors wanted them to know and failed to go beyond that."
Litigation is still pending against Eli Lilly & Co., the firm that was sponsoring the ill-fated trial. Another company, Oclassen Pharmaceuticals Inc., of San Rafael, Calif., had been involved in FIAU's earlier development.
The report was the third to look at the events of the drug trial.
An outside advisory committee to the National Institutes of Health, which sponsored the study, concluded that the deaths had resulted from delayed drug toxicity and could not have been foreseen. Earlier, in a harsher assessment, the Food and Drug Administration, which oversees drug research, faulted the researchers for being blinded by misplaced optimism in the drug and failing to recognize its ominous side effects. The FDA recommended new safeguards in the conduct of such trials.