Recombinant DMA Advisoiy Committee - 5/30-31/91 
and/or cell culture model systems and explain why the models chosen are the most 
appropriate." 
Dr. Mclvor said he felt this wording would indicate to the investigator writing the document 
that it will be their responsibility to demonstrate that there is some reason to expect that the 
procedure is safe and efficacious and that they must provide such data. He moved that this 
change in wording be adopted. Ms. Buc seconded the motion. 
Ms. Buc asked why the language called for "the most appropriate" model rather than simply 
that the model system chosen is appropriate to demonstrate safety, efficacy and feasibility. 
She said the requirement should merely be that the model suit the scientific purpose to which 
it is being put. Dr. Mclvor said that the availability of models is limited and in most cases 
what is being sought is a demonstration of gene transfer into human material, and in most 
cases he felt this is what the investigators will provide in the end. 
Dr. Anderson said he felt it was up to the investigator to determine what the most appropriate 
model was and that factors needed to be taken into account such as the expense and other 
problems of the model system. He said he felt the term "most appropriate” does not place 
additional restrictions on the investigators than is currently in place. 
Mr. Mannix said he was sympathetic to the proposed changes, but was concerned that some 
of the precedents being set may create inadvertent monopolies in that researchers may 
perceive that the only laboratory that's acceptable to the RAC for doing PCR amplification 
is the one currently being used by the researchers who have had protocols approved thus far 
and that it is not worthwhile to attempt something new because the RAC has already deemed 
this procedure as the most appropriate one. 
Dr. Mclvor said there were many techniques available to assess safety, efficacy and feasibility 
and PCR just happens to be one that is very sensitive. He noted there were different model 
systems that one could use to assess what might occur in humans which would provide 
preclinical data to assess the efficacy of the proposed procedure. 
Mr. Mannix said he was concerned with requiring demonstration of efficacy in a Phase I study 
where safety was the only issue being addressed. Dr. Mclvor responded that even in a Phase 
I study there must be some anticipation that the proposed protocol will eventually be 
efficacious and therefore preclinical data must be provided before such a procedure is 
launched. 
Dr. B. Murray said she felt one problem was the interpretation of the term "most appropriate," 
in that it could be interpreted in different ways and may provide a problem in assessing 
proposals. Dr. Anderson said the concern of most investigators he had spoken with was that 
they were concerned that the situation may occur in which the investigator has done 
everything that they think is appropriate, however a very influential or strong-willed member 
of the RAC or the HGTS might say, "I don't think that's the best model, that it should be 
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Recombinant DNA Research, Volume 14 
