Under the Microscope

In the aftermath of 18-year-old Jesse Gelsinger's death last September during a University of Pennsylvania gene therapy trial, intensified regulation of such studies will be a major topic at the American Society of Gene Therapy (ASGT) annual meeting, May 31-June 4 in Denver. "I think the important thing is to really keep focus," says society president Savio L. Woo, director of the Institute for Gene Therapy at Mount Sinai School of Medicine. "Medical research is a risky business, and we can't say there will be no risk involved .... Tragic incidents will occur, and when they do occur, we must learn from them and move onward." In February, President Bill Clinton asked Health and Human Services (HHS) Secretary Donna E. Shalala to instruct two of her department's agencies, the Food and Drug Administration (FDA) and the National Institutes of Health, to accelerate their review of gene therapy guidelines and recommendations. The following month, HHS announced two new initiatives. One is a series of gene transfer safety symposia, and the other is a monitoring plan to ensure appropriately independent clinical trial oversight. Sponsors of gene transfer trials now will be required to routinely submit their monitoring plans to FDA for review and possible changes, surveillance, and on-site inspections. "It's important to appreciate that what FDA and NIH are doing is not going to make it more difficult for researchers," Woo says. Improvements in clinical trial design, monitoring, and implementation can only be helpful to outcomes, he believes. "The results will be more informative." In an ASGT position statement, he remarks that Gelsinger's death, as well as others that reportedly occurred in trials here, have made it apparent that several aspects of patient adverse event reporting must be addressed. He calls for harmonization of reporting requirements between FDA and NIH, and closer examination of measures to protect patient privacy. He also requests appropriate resources for, and better processing of, data reported to governmental bodies. The society's third annual meeting will include new sessions on clinical trial compliance to be co-moderated by officials from FDA and NIH. As in the previous two meetings, an outreach program will target area high school science teachers, with lectures on the basic science of gene therapy, regulatory issues, and ethical implications of research. Inder Verma "The more we inform the public, the more we explain to them the potential dangers and potential benefits of gene therapy, the better it is," asserts the society's president-elect, Inder M. Verma, a genetics professor at the Salk Institute for Biological Studies. "I believe, personally, that stringent regulations are not going to hurt gene therapy. But I think, again, it's important that there is confidence among the public that regulatory authorities are performing their duties properly." He predicts that researchers will place more emphasis on their own concerns about potential toxicity. Moreover, "There will be less hype now, because they'll say, 'Wait a minute, let's see what we get.'" ASGT vice president Malcolm K. Brenner, director of the Center for Cell and Gene Therapy at Baylor College of Medicine, warns that NIH and FDA inspectors are used to examining large and complex Phase III pharmaceutical trials, or other such multifaceted systems as farms and food processing plants. Accordingly, their scrutiny will be detailed. "I think what everyone is worried about is the cost, because it's going to be a lot more expensive," he says. For example, the experimental process in gene therapy of going back and forth from lab to subjects now will entail a doubling of required tests, to more than 60 on each new compound, at prices ranging from about $750 to $8,000 apiece. Increased gene therapy trial monitoring probably won't influence the wider range of research involving human subjects, unless the Common Rule is altered. In 1991, HHS regulations concerning human subject protections became the basis of this policy, to which 17 federal agencies adhere. Any changes to the Common Rule call for the concurrence of all 17 agencies. In mid-April, the HHS Office of Inspector General (OIG) released a report on protecting human subjects that contains an update on responses by NIH and FDA to recommendations made two years earlier. Noting the new attention to gene therapy trials, the report says, "We continue to urge FDA and NIH to take similar initiatives directed at other research areas." However, it also acknowledges that "legislative change may well be necessary." Details of the ASGT annual meeting are available on the Society's Web site, www.asgt.org. Steve Bunk (sbunk@uswest.net)is a contributing editor for The Scientist.

Under the Microscope

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