Recombinant DNA Advisory Committee- 9/12-13/94 
an application to first pass a merit review to assure scientific credibility of the proposal 
before its own review? The issue will become important as consolidated review by NIH 
and FDA develops. A determination has to be made as to which proposal would require 
public review by the RAC. Dr. Varmus said that he is committed to the idea of retaining 
RAC purview of gene transfer protocols, especially when the methodology is novel. 
Finally, Dr. Varmus wanted an outside committee to provide some guidance for the NIH 
Director about how to respond to RAC recommendation for protocol approval, for 
example, in the event of a split vote. 
Dr. Parkman said that consistency of criteria in evaluating protocols is crucial. The Points 
to Consider in the Design and Submission of Protocols for the Transfer of Recombinant DNA 
Molecules into the Genome of One or More Human Subjects ( Points to Consider) is used as 
a yardstick to evaluate a protocol, but the medical, scientific and ethical criteria required 
for approval are not clearly defined. 
Mr. Capron advanced an idea that review of novel protocols by the RAC should set 
standards and expectations that could be used in the future by the FDA in its closed 
review of similar protocols not going to be deliberated by the RAC in a public forum. 
Points to Consider requires the investigators to address certain issues but does not provide 
guidance to judge the adequacy of responses from investigators to these questions. He 
said it is an appropriate time for an ad hoc group to articulate these review criteria based 
on the accumulated experience the RAC acquired while reviewing individual protocols. 
Dr. Varmus agreed that Mr. Capron identified an important problem. He said he is 
unsure whether a committee is able to put together a series of guideposts for protocol 
review. Even with a seemingly routine cytokine therapy for cancer, an investigator may 
propose a slightly different vector that warrants RAC deliberation. Without examining the 
submitted application, the appropriateness of a single review by FDA may not always be a 
straightforward decision. This is the reason that in the proposed NIH/FDA consolidated 
review procedure, a protocol will be evaluated by ORDA/RAC/FDA in order to 
determine its suitability to bypass the RAC process. 
Dr. Motulsky was strongly in favor of redefining the function of the RAC in dealing with 
scientific issues, ethical issues, and its relationship to other committees such as NIH Study 
Sections which review proposals for their scientific merit. He noticed the scarcity of 
scientifically competent peer reviewers within the RAC to deal with a wide range of 
applications, and often in need of referring to ad hoc outside consultants. He proposed 
the establishment of RAC to deal with issues unique to gene therapy. RAC was initially 
established to address special recombinant DNA aspects of gene therapy as a safety 
committee. Dr. Motulsky favored a return to this basic function. Currently, there is a 
division between the RAC functioning as a scientific committee and as a broader 
committee dealing with informed consent issues. This mixed function has caused some 
uneasiness among investigators. 
Dr. Miller asked what prompted the AIDS investigators to demand revamping the whole 
system of protocol review since there are only a few modest HTV protocols. In his 
Recombinant DNA Research, Volume 20 
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