NIH calls for stricter reporting protocols

A government advisory committee recommended a proposal requiring stricter reports of problems arising during gene-therapy experiments on Friday, during the final day of a National Institutes of Health conference addressing the issue. The proposal followed two days of intense scrutiny of the controversial Penn gene-therapy experiment that left 18-year-old Jesse Gelsinger dead in September. Some have speculated that Gelsinger's September 17 death could have been prevented if earlier problems in similar gene-therapy studies had been made public knowledge -- something the recommendation would have required. The proposed recommendation requires that all clinical studies in gene therapy be more stringently regulated in reporting of "adverse events" -- any serious medical problems resulting from experimental treatment, regardless of the problem's relationship to the gene therapy itself. And if the recommendation is approved, scientists -- whether doing an NIH study or working at an NIH-sponsored institution, like Penn -- must report any serious medical problem to the NIH within 15 days. The issue of stricter reporting, however, is problematic because while private companies want to keep details of their experiments under wraps for fear of disclosing "trade secrets," medical regulators advocate full disclosure of any information that could protect the safety of subjects. And while it may be bad for business to disclose this information, advocates of the proposal say that the novelty of the field necessitates the accessibility of as much information as possible so that experimenters can ensure patients' safety. "There is a balance that has to be struck," Director of the University of Minnesota Center for Bioethics Jeffrey Kahn said, between the proprietary nature of the experiments and the protection of patients. Friday's discussion by the NIH Recombinant DNA Advisory Committee -- the advisory group in charge of overseeing gene therapy experiments and protecting their subjects -- was prompted by reports that current rules regarding the reporting of adverse events were not being followed and that researchers were not submitting full reports to the NIH. Current regulations call for researchers in clinical studies to report any subject's serious medical developments to the FDA and NIH whether they are unexpected or related to the treatment. And while private researchers are presently required to report such incidents to the FDA, currently this information may not be released to the public without permission, on the argument that it is proprietary information. This provision lets researchers keep their information private by allowing them to report their problems to the FDA and not the public NIH -- leading some to fear that relevant and important medical information could be withheld from scientists doing similar research. The discussion on stricter problem reporting came two days after the U.S. Food and Drug Administration accused Penn's research team, led by James M. Wilson, director of the Institute for Human Gene Therapy, of having serious flaws in its study that led to Gelsinger's death. The FDA alleged during the first day of the NIH conference that the team failed to report serious side effects in the study's earlier participants and animal studies. The FDA also accused the team of allowing Gelsinger to participate in the study even though his liver was not functioning at the minimum required level. The researchers "responded to a wide range of questions fully and openly," University of Pennsylvania Health System spokesperson Rebecca Harmon said of the RAC session. "Our researchers continue to cooperate fully with the FDA review, which is ongoing," she said. Gelsinger's death was the first reported death caused by gene therapy, and drew nationwide attention to the emerging field that once promised to cure diseases from cancer to cystic fibrosis. It now has the added promise of financial reward for private biotechnology companies. Gelsinger was part of an experiment that aimed to find a cure for a liver disorder called ornithine transcarbamylase (OTC) deficiency. He was missing the gene that made the OTC enzyme, and could not digest ammonia, a poisonous by-product of protein digestion. The Arizona native died four days after being injected with a genetically altered virus that was supposed to trigger healthy enzyme production in his liver. The investigation into his death, discussed on Thursday, found the main cause of death to be lung failure. Friday's proposal is important to all areas of scientific research that use human subjects, Kahn said, adding that Gelsinger's death was a specific case where fuller disclosure of adverse events may have saved him. As for the future of gene therapy, the effects of Gelsinger's death on the field remain unclear. Kahn said researchers will probably be more cautious, and the pace of research may slow. "But there are real people's lives put in harm's way in these studies," he said. And if research is slowed until regulations are sorted out, he said, "that's what we have to do."

Please note All comments are eligible for publication in The Daily Pennsylvanian.