The Food and Drug Administration yesterday issued a firm reminder to doctors and pharmaceutical company researchers involved in gene therapy studies that they are required to tell federal health officials immediately about any deaths or other serious side effects among patients who have received gene therapy.
The letter came two days after The Washington Post reported that two research teams had failed to provide such notification for six patients who had died after receiving gene therapy in the past 19 months. The researchers said they had reported the deaths promptly to the FDA, which generally keeps such information secret, but not to the National Institutes of Health, which also oversees gene therapy but reviews injury reports publicly.
In yesterday's letter, Kathryn Zoon, director of the FDA's Center for Biologics Evaluation and Research, also put researchers on notice that the agency will turn death and injury reports over to the NIH if the researchers do not.
Gene therapy seeks to cure inherited diseases and cancer by giving patients new genes. Because the science is still new and unproven, and because genetic manipulation is controversial, the field has been held to a higher standard of public scrutiny than conventional medical experimentation.
For example, all researchers who gain federal approval to conduct gene therapy studies get a letter from the NIH saying they must "immediately report unexpected or serious adverse events" to the NIH Office of Recombinant DNA Activities (ORDA), in addition to the FDA and other agencies to which other researchers must report.
Tufts University researcher Jeffrey Isner failed to report two deaths to ORDA in a study of gene therapy for heart disease. Ronald Crystal at New York Hospital-Cornell Medical Center didn't report four deaths to ORDA in a competing heart disease study, and an additional death in a study of blocked blood vessels in the leg. Crystal reported one other heart study death to ORDA but with an unusual request that it be kept confidential.
Earlier this week, the two researchers said the deaths were not related to the gene therapy but to the patients' underlying illnesses, and they did not believe they were required to report them promptly to ORDA. They said they told the NIH about the deaths in summary reports recently requested by ORDA, and in response to a special appeal from the agency for any unfiled reports of deaths or illnesses. The appeal followed the death in September of a teenager undergoing gene therapy at the University of Pennsylvania, thought to be the first directly caused by a genetic treatment.
Amy Patterson, director of ORDA, said summary filings provide too little information too late. "The guidelines are quite clear on this that serious adverse events are to be reported immediately," she said.
Moreover, she said, the rules require all deaths and serious illnesses to be reported, regardless of whether they seem to have been caused by the therapy, because all information can be helpful in such a new field of research and subsequent research might prove those conclusions wrong. The FDA notice to that effect was prominently posted yesterday on the agency's Web site and forwarded to the NIH, which may distribute the notice directly to researchers.
On Thursday, Sen. Bill Frist (R-Tenn.) sent a letter to NIH chief Harold Varmus expressing his "great concern" about the cases in which deaths were not reported to the NIH.
"I was troubled that these deaths were not reported to the NIH, and it raises several questions regarding the clarity and enforcement of NIH guidelines for gene therapy research," wrote Frist, who is a member of the Health, Education, Labor and Pensions Committee.
Frist asked Varmus to provide details of the controversy to him within two weeks, including an explanation of how the NIH intends to ensure that any lack of compliance with federal regulations does not happen again.