Recombinant DNA Advisory Committee - 2/4/91 
research efforts. He then called on Dr. Mclvor to present the next agenda item. 
PRECLINICAL DATA (ANIMAL MODELS) FOR HUMAN GENE THERAPY 
PROTOCOLS: 
Dr. Mclvor noted that the HGTS had approved 5 protocols, two of which would be 
before the committee today for consideration, and that the RAC had already approved 
three such protocols. However, in all cases there seemed to be good reasons why good 
preclinical data could not be provided with the protocols. He was concerned that a 
major policy was being set as a result of the case-by-case consideration of these 
protocols, and it was time the committee considered the role and expectations of 
preclinical studies in human gene transfer protocols, separate and apart from any specific 
protocol being discussed. 
Dr. Mclvor said it was apparent to anyone considering human gene therapy that 
experiments in animals are of the utmost importance to demonstrate the feasibility of 
proceeding to human trials. This approach sets an extensive precedent in the evaluation 
of new clinical therapies for human disease. However, Dr. Mclvor was concerned that, 
unless the RAC takes the time to clarify its expectations in this regard, investigators 
submitting protocols in the future will consistently fall short in supplying such data. 
Dr. Mclvor said that perhaps the Points to Consider document should be modified by 
incorporation of a phrase such as "results demonstrating the efficacy and feasibility of the 
proposed procedure using the most relevant animal and/or cell culture model systems 
should be included." This would be a stronger statement than what is currently 
contained in the Points to Consider, which simply asks the investigator to describe results 
obtained in preclinical studies. He asked that this item be placed on the agenda for the 
next RAC meeting and said he would welcome comment from the rest of the committee 
on this issue. 
Dr. Anderson said that it was true that the protocols that had come forward to this point 
had not had substantial animal studies on efficacy, but added that this was because of the 
lack of animal models. In contrast there were substantial adequate safety studies 
performed in animals to address issues of safety and that it was only the efficacy studies 
which were lacking. 
Dr. Mclvor understood this but noted that efficacy was an issue to be considered in 
determining feasibility. He was afraid that the message being sent to investigators was 
that there is no necessity to do animal work. 
Dr. McGarrity asked Dr. Walters if this issue could be brought before the HGTS at its 
next meeting. Dr. Walters ensure that it was placed on the agenda for discussion at the 
Recombinant DNA Research, Volume 14 
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