After 4 decades of vetting clinical trials of gene therapy for novel risks, it’s time to relax a bit, says a report issued today by an expert panel.  But key government officials are greeting the recommendation with caution.
Gene therapy has proved its value, and its leaders have managed ethics issues well, according to a panel convened by the Institute of Medicine (IOM) at the U.S. National Academies. The long-term hazards of gene therapy may not be clear yet, but the general risks seem no greater than in other areas of experimental medicine, the report says, so it’s time to phase out the U.S. outfit created in 1974 that’s dedicated to reviewing gene therapy, the Recombinant DNA Advisory Committee, or RAC.
“[M]any of the original fears associated with gene transfer”—such as worries about creating new pathogens, modifying the human germ line, or injuring society in other ways—“have not been borne out,” the IOM panel concludes. At the same time, it finds that “public perception has largely transitioned from negative to positive” thanks to gene therapy’s success in treating disorders such as inherited blindness and hemophilia. The panel urges the National Institutes of Health (NIH), which houses RAC and uses its advice, to stop having RAC examine individual gene therapy protocols.
The IOM report hedges this recommendation, however. While the old RAC should go out of business, the panel says, another RAC-like body should take its place, and with a broader mandate—to examine all forms of risky clinical research that other agencies may not be able to vet adequately. The IOM group also urges the U.S. government to keep RAC going until a successor is created. During the transition, the IOM report says, RAC reviews should be streamlined to make life easier for researchers, and individual protocols should be examined only “in exceptional circumstances, such as when novel gene therapy technologies and treatment strategies move forward into the realm of clinical trials.”
Gene therapists have long complained about the burden of RAC reviews. Like other clinical researchers, they must get approval for trials from ethics and biosafety panels at their own institutions; they must also clear clinical trials in advance with the U.S. Food and Drug Administration (FDA). But gene therapists have an extra duty other researchers do not have: They must file a detailed description of proposed experiments with RAC. Unlike FDA, RAC releases these proposals and may hold a public hearing on them before approving a trial. Last year, gene therapists’ main professional society issued a public appeal to end RAC’s duplicate review . NIH asked IOM to look into this matter, and the report issued today is the outcome of NIH’s request.
The IOM panel’s chair, Lawrence Gostin, a public health and law professor at Georgetown University in Washington, D.C., says that he was well aware of gene therapists’ unhappiness about multiple reviews. Their dismay “came through loud and clear,” during public comment sessions, Gostin says. The IOM panel report says that most gene therapy trials should now be reviewed only by FDA, but it also recommends that proposed gene therapy trials continue to be registered in an open docket. But researchers should be required to file only one protocol, the one prepared for FDA review. It seemed “prudent” to keep the tradition of open access to information in this field, Gostin says. RAC has served an “enormously useful purpose,” Gostin says, by reassuring the public about the safety of this new and once-worrisome field and by aggregating data everyone finds valuable, particularly clinicians.
NIH Director Francis Collins, after being briefed on the IOM report, issued a noncommittal statement today thanking the panel for its work and saying that NIH “will be taking a close look at the study’s findings and recommendations and will determine the best path forward in light of our shared interest in doing what’s best for patients and for continued progress in the field.” The American Society of Gene & Cell Therapy, in an equally cautious statement, said today that it “looks forward” to Collins’s “review of and decisions based on the IOM’s findings.”