A National Institutes of Health official acknowledged yesterday that researchers routinely fail to report problems in gene therapy trials, and pledged that the agency would step up oversight of the medical experiments.
"We are deeply concerned about the under-reporting of serious adverse events to the NIH, and we are taking steps to better understand and address the problem," said Amy Patterson, director of the NIH office of biotechnology activities.
NIH will begin more inspections of research labs and will find ways to ensure that more information about side effects in clinical trials is made public, Patterson said.
Speaking before a Senate subcommittee, Patterson joined academics, Congress members and other health authorities in an inquiry prompted by the death in September of Jesse Gelsinger, an 18-year-old who participated in a gene therapy trial at the University of Pennsylvania.
His death, believed to be the first directly caused by an experimental gene therapy, prompted an investigation by the Food and Drug Administration. The agency found that Penn had violated rules designed to protect patient safety and shut down its gene therapy program two weeks ago.
Throughout the hearing, health officials and senators offered condolences to Gelsinger's father and vowed that the boy's death would not be in vain.
Paul Gelsinger led off the hearing, saying he and his son had been misled by researchers at the university when they signed up for a therapeutic trial to treat a genetic liver disorder. Jesse suffered from a mild form of the disease. Both father and son were told in July, Gelsinger said, that a patient in the clinical trial had shown a 50 percent improvement. In December, he said, he learned that the patient had not improved at all.
Gelsinger also said he learned only after his son's death that several other patients suffered liver damage during the experiments and that monkeys had died during animal trials.
"If you have people putting their lives on the line, they have a right to have access to the research," Gelsinger said. "I was under the impression that this was a field that was progressing. But I was mistaken. It was an experiment."
After the death became public last fall, NIH contacted all genetic therapy projects under its jurisdiction. The agency discovered that of 691 instances of serious side effects among people involved in gene therapy experiments over the past seven years, only 39 had been reported immediately, as required by law.
Sen. Bill Frist, a Tennessee Republican, pressed federal health officials to explain what he repeatedly pointed to as a "breakdown" in oversight.
Patterson of the NIH said that researchers do understand the institutes' guidelines for reporting health problems during genetic trials because they are often stated and recapitulated.
"They should know," she said, concluding that many had simply violated federal guidelines.
While the NIH and FDA are reevaluating their practices to ensure better oversight, Jay Siegel of the FDA said that most of his agency's inspection efforts occur right before drugs come to market, not during clinical trials. The reason, he said, is a "resource issue."
Jesse Gelsinger's death raises questions about the complexity of genetics research, said Frist, who is a physician and chairman of the Senate Subcommittee on Public Health. Regulators must reconsider what it means to give informed consent, how to protect the privacy of patients who do not want their health problems revealed, how to ensure their safety, and how to address the desire of industry to protect proprietary information.
Despite the hoopla generated when the field of gene therapy emerged a decade ago, rapid scientific advances have been accompanied by "great hype and unrealistic expectations," said Inder M. Verma, director of the genetics lab at the Salk Institute, who also testified yesterday.
Approximately 6,000 people have participated in gene therapy trials, but no one has been cured of any disease.
"The excitement was genuine," Verma said. But since then, "there were unexpected hurdles and the immunological consequences were unforeseen. Did we start too soon? Should we have done more animal model studies? Was there adequate preclinical data?"
Tragic incidents like the death of Jesse Gelsinger, he concluded, "give a reason to pause and take stock of the progress and pitfalls of the technology. We must learn from our mistakes."