GENE THERAPY: Scrutiny Increases as Docs Deny Wrongdoing
Contradicting federal health officials, Boston heart researcher Dr. Jeffrey Isner said his company informed the NIH about two deaths that occurred recently during his gene therapy research, the Boston Globe reports. But NIH spokesperson Donald Ralbovsky stated that Isner failed to report the deaths immediately, noting "The guidelines are clear and specific on that matter." This week, NIH officials said that Tufts University's Isner and rival New York Hospital-Cornell Medical Center researcher Dr. Ronald Crystal failed to report a half-dozen deaths that have occurred in the doctors' gene therapy trials. The Globe suggests that research jurisdiction is at the heart of the conflict, which is erupting "just as results of the first large-scale human studies of various gene therapy approaches are emerging." Both Isner and Crystal profess to have reported the deaths immediately to the FDA, as required by law. NIH officials, however, noted that FDA reports remain confidential, preventing the adverse effects from being widely disseminated. The NIH, which maintains "looser authority" over gene therapy research, argues that study deaths should also be reported to NIH officials so that the information can be made public (Knox, 11/4). Moreover, NIH administrators note that failure to report adverse gene therapy effects could lead to the "suspension, limitation or termination" of further NIH gene therapy funding for the researcher and or the research institution. But Isner stated that the NIH rules -- unlike the FDA regulations which provide reporting requirements based on the severity of the adverse patient effect -- are "ambiguous at best." Dr. Crystal concurs, stating that calling for reports on "every adverse event -- even those unrelated to the gene therapy -- is impractical," the Wall Street Journal reports (Adams, 11/4).
Gene Therapy Not the Cause
Both physicians deny that the patient deaths -- of which Isner and Crystal have reported eight -- were due to adverse effects from gene therapy, but were instead caused by complications from other pre-existing conditions. In addition, the doctors noted that the FDA agreed gene therapy was not responsible for the deaths, allowing the studies to go forward," (Boston Globe, 11/04). A spokesperson for Parke-Davis, one of Dr. Crystal's research sponsors, said, "There was at no time any attempt to withhold any adverse-event information. What's at issue here is an interpretation of the guidelines" (Adams, Wall Street Journal, 11/04).
What's That Again?
But many are beginning to question Isner's and Crystal's "interpretations," as both scientists own stock in the research companies and stand to benefit from the research outcomes (Knox, Boston Globe, 11/04). The New York Times reports that today a spokesperson for Schering-Plough Corp. said that three liver cancer patients participating in the firm's research have experienced serious side effects that might have been related to their therapy. The patients, according to the spokesperson, have been treated similarly to the 18-year-old man who died unexpectedly six weeks ago in a University of Pennsylvania gene therapy experiment. In the wake of the UPenn death, the FDA temporarily halted two Schering-Plough gene experiments involving adenovirus, which has been used for the treatment of liver cancer. Subsequently, the NIH has requested that all scientists using adenovirus to submit all data regarding patient safety. "We don't know whether [the death] is a freak incident or the beginning of a trend," said American Society for Gene Therapy President Dr. Savio Woo. He noted, "That has to be critically evaluated by the FDA," and the NIH's Recombinant DNA Advisory Committee (RAC). The data will be made public on December 8 and 9 at a meeting of the RAC -- the NIH gene therapy protocol review panel (Stolberg, 11/04).