FIAU Update

Last fall, in the aftermath of the clinical trials of the drug fialuridine (FIAU) to treat hepatitis B patients, NIH and FDA reviewed various aspects of the FIAU studies that resulted in five deaths. In September 1993, FDA held a public hearing, and in November 1993, the agency issued its report on hepatic and pancreatic toxicities associated with FIAU. In May 1994, FDA sent a series of letters criticizing certain aspects of the studies to the participating principal investigators and drug companies.

However, the NIH Subcommittee to Review FIAU Studies reached different conclusions in a June 2, 1994, report to the Advisory Committee to the Director, NIH. After a thorough review of patient records, protocols, and supporting documents, and interviews with principal investigators, staff, and patients the Subcommittee concluded that "there was a justifiable scientific rationale for the NIH FIAU studies" and that "the FIAU studies represent the best of current practice in clinical investigations and exceeded regulatory requirements where such applied." The Subcommittee also concluded that "delayed, fatal human liver toxicity due to FIAU represents a novel type of toxic reaction not previously encountered."

The Subcommittee's report ended with a few specific recommendations on mechanisms of toxicity, preclinical animal tests, patient enrollment, and patient follow-up and its concluding statement recognized the intrinsic risk in conducting clinical trials: "Risk in research cannot be avoided, although we do our best to minimize it. This tragedy will chasten all investigators to remain vigorously alert to the unusual, unexplained or unanticipated in the research process. It also re-emphasizes the importance of understanding risk for their partners in the process -- the patients for whom the whole enterprise exists."

In an addendum to the report, the Subcommittee also commented on the FDA's letters to the NIH investigators, which indicated a series of failures on the part of the investigators. The Subcommittee recognized that the Institute of Medicine Committee, to be convened in July 1994 by the Assistant Secretary for Health, will need to reconcile the apparent differences in the conclusions of the FDA auditors and the NIH Subcommittee to Review FIAU Studies. Finally, in responded to a request from Congressman Edolphus Towns (D-NY), Chairman of the Subcommittee on Human Resources of the House of Committee on Governmental Operations, NIH supplied him with copies of documents, patients' records (with personal identifiers masked out), and Subcommittee meeting notes in late June.