Washington

Bench-top bothers: there are fears that tighter RAC review could slow down clinical trials. Credit: PAUL A. SOUDERS/CORBIS

The US National Institutes of Health (NIH) was last week urged to give its Recombinant DNA Advisory Committee (RAC) a greater role in the regulation of clinical trials for gene therapy. The call came from a working group set up to advise the NIH in the face of increasing concern over the conduct of such trials.

The advice runs counter to the policy of the former NIH administration, which had sought to diminish the RAC's involvement. It is also contrary to the wishes of clinical investigators, who are concerned about increasing amounts of red tape. But with legislators pushing for tighter control on clinical trials, such a move could reduce the pressure for congressionally mandated regulation.

Under the new proposals, enrolment in a clinical trial would not begin until the RAC had accepted the trial's protocols. If the committee found that a protocol was novel — because, for example, it used a new kind of vector to deliver a gene, or sought to treat a new group of patients — the trial's investigator would have to present it formally to the RAC, which meets four times a year. Only after the committee was satisfied with the protocol would enrolment begin.

Christine Cassel of Mount Sinai Medical Center, and co-chair of the working group, told the NIH director's advisory committee meeting last week that only about 10 per cent of protocols would be subjected to this higher level of scrutiny. Before the new guidelines can come into effect, they need to be endorsed by acting NIH director Ruth Kirschstein, who has asked her advisory committee to comment on the proposals.

Claudia Mickelson, biosafety officer at the Massachusetts Institute of Technology, RAC chair and a member of the working group that drafted the recommendations, denies that the RAC review would slow down the clinical-trial process. The proposals call for simultaneous review by the investigator's institutional review board, institutional biosafety committee and the RAC. Until now, such processes have been conducted sequentially.

In the past, novel protocols were sometimes reviewed by the RAC at the same time that investigators were enrolling patients, or even proceeding with the trials. “That's an untenable situation,” says LeRoy Walters, former RAC chair and director of the Kennedy Institute of Ethics at Georgetown University in Washington DC, who has long been calling for the body to have more regulatory authority. “That just promotes disrespect.”

Walters also notes that the new guidelines emphasize that the RAC is an advisory body to both the NIH and the Food and Drug Administration (FDA). These two bodies have sometimes had difficulty communicating with each other — especially over adverse events in clinical trials. This is another area the working group hopes to address, by harmonizing reporting to both agencies.

Even if the FDA recognizes the RAC as an advisory body, Walters says he has a “nagging concern” that gene-therapy trials funded and carried out by pharmaceutical companies could never have their adverse events made public. The RAC aims to disseminate such information in order to detect patterns and prevent the use of dangerous vectors, but the pharmaceutical industry is keen to keep adverse events confidential.

“We don't know that there aren't human gene-transfer protocols that have been submitted to the FDA that are totally invisible to the public review process,” says Walters.