"TRIAGE" REVIEW PROCESS PROPOSED FOR GENE THERAPY PROTOCOLS BY NIH AD HOC RAC REVIEW COMMITTEE; NIH SHOULD CONTINUE TO FOSTER GENE THERAPY RESEARCH

A "triage" procedure to streamline gene therapy protocol review should be considered by the National Institutes of Health, the ad hoc review committee to the Recombinant DNA Advisory Committee proposed at its March 8 meeting in Bethesda, Md.

"The major problem with RAC is that investigators are allowed to [submit] incomplete data," member Charles Epstein, MD, University of California-San Francisco, stated. Commenting that R01 grant applications would not be submitted to NIH in such a condition, he asserted that "there needs to be some mechanism that would make it very clear what is expected by RAC." Committee Chair Inder Verma, PhD, Salk Institute, agreed there should be "certain minimum standards" for submission of scientific data and informed consent information.

Under the proposed triage process, each applicant would be required to submit a "checklist" that included the minimum scientific data requirements, such as data on vector sequencing and transduction efficiency. The Office of Recombinant DNA activities staff would review applications for the minimum standards. If an application was found to be lacking, it would be returned to the investigator. Consultation on some applications could be done by as many RAC members as ORDA deemed necessary.

The proposal would differ from the current overall NIH triage system as it would only turn away applications for incomplete data. Under NIH triage, all R01 and R29 grant applications receive scientific review and the lowest-ranked applications are deemed "non-competitive."

In other recommendations, the committee suggested that NIH create a gene therapy study section. "There really is no good mechanism by which gene therapy grants are reviewed in study sections," Verma maintained, and, as a result, "a lot of young investigators are precluded from coming to this field." If a study section were established, "it might help improve the quality of the grants and the perception of a fair review," he said.

The issue of gene therapy centers of excellence raised by NIH Director Harold Varmus at the first ad hoc group meeting was also revisited ("The Pink Sheet" Feb. 13, p. 17). Agreeing that the field of gene therapy research needs the stimulus of such centers, the group cited specific areas that warrant attention such as virus, vectorology, delivery systems, cell biology, model systems and Good Manufacturing Practice facilities.

The committee also suggested that NIH should choose the funding vehicle for the centers, whether it be through requests for applications [RFAs], P01s or possibly the National Heart, Lung & Blood Institute's SCORE (Specialized Centers of Research Excellence) mechanism.

There are three "concrete" obstacles to advancement in the field, member Robertson Parkman, MD, Children's Hospital, Los Angeles, commented. They are: the need for better delivery systems; the regulation of gene expression; and the cost of producing clinical grade reagents.

Although he agreed that NIH needs to jump-start gene therapy research through the centers concept, Verma expressed some concern. "I have my own bias -- that is that the rich become richer very often" through centers of excellence. Verma noted that at institutions such as Johns Hopkins University, "they already have all these people there. If they decide to put them together, then this is an opportunity for extra money for them. And they might not necessarily do something great."

The group also recommended that NIH convene a one-day meeting, possibly in September, to review the outcomes of past protocols. Noting that at present NIH does not have such information, Verma maintained that the symposium would "help in improving the overall quality of science."