U.S. Wants More Sunlight on Researchers

Federal health officials said Wednesday that they will seek stricter enforcement of guidelines requiring federally funded medical researchers to promptly report all deaths or serious side effects that occur during the course of experimental medical treatments.

The comments came in the aftermath of the death of an 18-year-old Arizona man who received gene therapy for a rare genetic disease. The Food and Drug Administration and the National Institutes of Health, which oversee such research, are investigating the September death, including possible lapses by the study’s principal researchers in reporting potentially serious side effects, as well as other violations of research procedures.

FDA and NIH officials stressed that scientists must abide by these federal rules--which require reporting to both agencies--and said that researchers cannot declare their reports confidential to prevent them from being shared with other researchers or the public.

The FDA is not allowed to publicly release the information; the NIH is under no such restrictions.

Lana Skirboll, director of the NIH’s office of science policy, said that both agencies plan to exchange information each receives more often so “if an investigator has not submitted something to the NIH, we will know from the FDA.”

Until recently, she added, “we didn’t know what we didn’t know.”

Under revised guidelines proposed recently by the NIH, researchers would have to report deaths and adverse events to both agencies within 15 days, even if the illnesses do not appear related to the therapy. Also, such reports should not contain “proprietary or trade secret information” or any “individually identifiable patient information,” so they may not be declared confidential.

The proposed revisions must undergo a period of comment of several months and may be changed before becoming final.

Skirboll’s remarks Wednesday came during the first of three days of hearings by the NIH’s Recombinant DNA Advisory Committee. The committee, which publicly reviews genetic research and offers recommendations to the NIH, is examining the latest events involving gene therapy--a promising field that is under intense scrutiny as a result of its first patient death and the ensuing investigation.

Gene therapy, which has been under study for 10 years, is viewed as a potentially cutting-edge approach to treating numerous diseases caused by genetic flaws. The treatment involves finding ways to introduce healthy genes into the body that can repair or replace defective ones.

More than 300 gene therapy studies are underway, and at least 2,500 patients have been treated, without apparent harm.

The FDA is looking into the death of Jesse Gelsinger of Tucson, who suffered from an often-fatal disorder called ornithine transcarbamylase deficiency, which prevents the liver from breaking down ammonia, a byproduct of protein digestion. He had volunteered for experimental gene therapy at the University of Pennsylvania’s Institute of Gene Therapy.

Gelsinger died after researchers infused a genetically modified virus, called an adenovirus--one cause of the common cold--into his liver in an attempt to introduce genes that could correct those responsible for his disorder.

Researchers said Wednesday that Gelsinger died of acute respiratory distress syndrome, although it is unclear exactly what role the gene therapy may have played.

The FDA is investigating whether researchers violated several federal guidelines in conducting the study, among them the fact that Gelsinger was included even though his health status apparently did not meet entry requirements.

Kathryn Zoon, director of the FDA’s center for biologics evaluation and research, said that the agency is looking into two possible “deviations” from required rules in the case, including whether Gelsinger should have been treated at all.

University of Pennsylvania researchers have denied the accusations and are scheduled to offer a detailed defense of their work at today’s hearing. Reading from a brief statement Wednesday, chief researcher James M. Wilson said that, when Gelsinger enrolled in the study, his blood ammonia was at acceptable levels but later increased to levels higher than those set under rules prearranged by researchers and the FDA. Wilson said, however, that he believed the FDA rules pertained to the period when Gelsinger first enrolled.

After the hearing, Gelsinger’s father, Paul, said that he does not blame Wilson for his son’s death. “I touched souls with this man,” Gelsinger said. “There is nothing wrong with Wilson.”

The case has sent a collective chill among researchers who see the work as the most exciting and promising in the treatment of genetically based diseases.

USC’s W. French Anderson, who a decade ago was among the first to conduct a gene therapy experiment, delivered an impassioned defense of the field before the advisory committee Wednesday.

“Cutting-edge medical research is risky. Bad things happen,” Anderson said. “. . . If mistakes were made, they were honest mistakes made by compassionate physicians desperately trying to help their patients.”

The Washington-based Biotechnology Industry Organization expressed some reservations about the broadened guidelines, particularly the requirement that every death or serious illness be reported. Such a rule, the group said in a statement, “could be detrimental to the development of potentially life-saving new therapies.”