Tougher Gene Therapy Protections Urged

The Clinton administration announced Tuesday that it intends to strengthen existing protections for patients in gene therapy research as well as for volunteers in all biomedical research. And for the first time, it proposed hefty fines for researchers who break the rules.

Health and Human Services Secretary Donna Shalala told reporters at a briefing that the federal government also will begin monitoring research at earlier stages than it does now--even when only small numbers of patients are involved--and will ask Congress to give the Food and Drug Administration authority to levy penalties of $250,000 on individual researchers and $1 million on institutions.

“This is a clear message that we intend to get serious,” Shalala said. “We need to get back to some basics--this is not about needing new rules or changing a set of rules--we need to make sure that people are following the rules.”

In recent months, federal health agencies, including the FDA and the National Institutes of Health, have announced a series of measures aimed at cracking down on federally funded researchers who conduct risky gene therapy studies. These measures include examining past records and increasing safety monitoring and site visits.

Tuesday’s action was meant to extend and expand many of these same rules to the conduct of all research, not just gene therapy.

Shalala and officials of the FDA and NIH, all of whom oversee federally funded research, stressed that they do not believe dangers to the public have increased.

Instead, they said, they are seeking to restore public confidence in a field that, while beleaguered, holds “the potential for extraordinary breakthroughs,” Shalala said.

The “Golden Age” of biomedicine will continue “only if the public has full confidence in the researchers and the institutions,” she added.

Noting that biomedical research in recent years has become more sophisticated and complex, she said: “We are trying to get ahead of a world that is changing under our feet.”

The measures were applauded by the biotechnology industry, which cited a report last month by French researchers as proof that the research investment is paying off. The French team successfully used gene therapy to treat infants born with a life-threatening immune disorder.

The patient trials are extremely important in finding cures for “untreatable disease,” said Michael J. Werner, director of federal government relations for the Biotechnology Industry Organization, which represents more than 920 companies, academic institutions and biotech centers.

Gene therapy research has been controversial since the death last September of 18-year-old Jesse Gelsinger of Tucson, who had received gene therapy for a liver disorder as a patient at the University of Pennsylvania’s Institute of Gene Therapy. After his death, FDA investigators determined that the institute had violated several regulations in its conduct of the research and shut down the program. It has also clamped down on several Boston gene therapy researchers.

FDA Commissioner Jane E. Henney said that the agency has launched a pilot program to examine 70 ongoing gene experiments “to see if we have a deeper, broader problem in this arena.” But the results of the inquiry have not been completed.

Outlining the actions, many of which will be effective immediately, Shalala said that federal agencies now will:

* Ask Congress to approve legislation giving the FDA authority to impose civil monetary penalties for violations of informed consent or other procedures of as much as $250,000 for clinical investigators and as much as $1 million for research institutions.

The agency only has the power to halt research until problems are fixed. Financial punishment will be “something that will get their attention immediately,” Henney said.

The legislation will be sent to Congress “as soon as it’s drafted,” Shalala said, although it is not clear whether Congress will have time to act on it this year.

* Require researchers to submit safety monitoring plans to the NIH earlier in the research process--as early as the time they apply for NIH funding--rather than after trials are well underway.

* Undertake an aggressive effort to improve the education and training of researchers, institutional review boards--panels whose members review patient protection plans for each study--and staff members of research institutions. Such training now will be required to receive NIH funding.

* Issue specific guidelines regarding informed consent, the process of explaining to patients the potential risks and benefits of participation.

For particularly risky or complex clinical trials, institutional review boards will be expected to take additional measures to ensure compliance with informed consent procedures, for example, involving a neutral third party to observe when a patient is being informed of the dangers and benefits.

* Issue additional guidance to researchers to clarify its rules regarding potential conflict-of-interest situations. The department plans to sponsor a series of public meetings this summer to discuss better ways of managing conflict of interest so that research is conducted objectively.