By Lisa Seachrist

Washington Editor

WASHINGTON - A draft report of an NIH working group recommends the Recombinant DNA Advisory Committee (RAC) monitor and make public all serious adverse events that occur in gene therapy clinical trials.

The Working Group On NIH Oversight of Clinical Gene Transfer Research was charged with evaluating the regulation in the wake of the death of an 18-year-old gene therapy patient last September and subsequent revelations that gene therapy researchers weren't reporting adverse events to the NIH and the RAC. In a leaked draft dated June 2, the working group has recommended the RAC take a more active role in overseeing gene therapy trials and analyzing adverse events associated with the trials.

The recommendations conflict with the desires of the biotechnology industry, which stated publicly at RAC meetings in March that the FDA, not RAC, had the regulatory authority and expertise to monitor the gene therapy trials' adverse events. The committee itself has questioned whether it is equipped to adequately analyze the adverse events.

RAC was established in 1975 to create appropriate biological and physical containment practices and procedures for recombinant DNA research. In 1990, RAC was charged with conducting a case-by-case review of gene transfer experiments and approving those protocols. In 1991, RAC ceded oversight of environmental release of genetically modified organisms to the Department of Agriculture and the Environmental Protection Agency. As gene transfer experiments became more routine, the NIH diminished RAC's role and removed its approval authority.

In the draft report, the working group notes it is "likely that the loss of approval authority had multiple, potential adverse impacts on the oversight of gene transfer clinical trials. These negative effects included: 1) the loss of the ability of RAC, through the approval process, to make informative and effective policy statements about the types of trials that were considered acceptable on scientific and ethical grounds; and 2) the sense expressed by many that the loss of authority made service on RAC less desirable and sent a message to the gene transfer community that the committee's recommendations were not important."

In the draft report, the working group all but gives back approval authority to RAC even though it acknowledges the NIH is not a regulatory agency and RAC is not a regulatory body. The draft states that "safety will be best protected if subjects are not enrolled in novel gene transfer trials until RAC discussion has occurred and its recommendation responded to by the investigator."

The working group reaffirms RAC's authority to collect reports of serious adverse events from gene therapy investigators, at least until the FDA implements a proposed rule to make that information public. Industry has opposed making the adverse events public, arguing it likely would confuse people without helping researchers.

In addition, industry has raised concerns that the release of raw data would expose gene therapy volunteers to loss of privacy. The working group proposes to deal with that issue by stating "all measures must be taken, within reason, to protect the privacy of the individuals without compromising the health of others in similar trials."

The draft report calls for the FDA and the NIH to harmonize reporting of serious adverse events. Currently, the FDA receives expedited reports from sponsors when the adverse events are both serious and unexpected. The NIH is supposed to receive reports of all serious adverse events immediately after they have occurred from the study investigators. Industry is on the record saying the reporting requirements should be harmonized to the FDA standards and reports should go to the FDA - the agency with the authority to place clinical trials on hold.

The working group's recommendations appear to be in conflict with the desires of at least some members of RAC. In the committee's March meetings, several members expressed concern that RAC lacked the expertise and logistical support to monitor adverse events in gene therapy trials. The working group calls for the NIH and its Office of Biotechnology Activities to establish a subcommittee of RAC to conduct ongoing analyses of adverse events data. That subcommittee would review all reports of adverse events, analyze data trends, develop a cumulative report that would be presented annually at a public RAC meeting and made available to the public, and identify trends or single events that may warrant further public discussion or federal action.

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