July 30, 1990, Human Gene Therapy Subcommittee 
Standard design for such studies. 
Dr. Epstein asked how the subcommittee was to view the trial, since up until now the 
subcommittee had thought that efficacy was one of the primary issues to be discussed. 
By definition, a Phase I trial is primarily for determining maximum tolerated dose. Dr. 
Walters said that during the past two years of discussion of human gene therapy 
protocols, the emphasis had gone from looking at the protocols as diagnostic studies with 
no emphasis on efficacy, to placing a high emphasis on efficacy in the ADA protocol, to 
now a third category of emphasis on safety, but with some attention to efficacy as well. 
Dr. Leventhal said she felt there were two aspects to efficacy in a human gene therapy 
trial: (1) the efficacy of the technique, that is, the gene can actually be inserted and one 
is able to determine that insertion took place; and (2) what people normally view as 
efficacy of a treatment, such as the efficacy involved in drug or radiation therapy where, 
despite toxicity, a maximum tolerable dose is administered. 
Dr. Epstein said he viewed efficacy as a reasonable expectation that a therapy is going to 
work. He said that what he wanted to know is what minimum requirement the RAC and 
the HGTS were to place on a demonstration of expected efficacy involving human gene 
therapy protocols. He said the whole issue of the questioning by the subcommittee on 
the ADA protocol centered around issues of efficacy of the treatment. He asked that 
this issue be clarified. Dr. Mulligan said that it was important, in order to look at 
efficacy, to initially ask at what dose it may be detected. This is the type of proposal 
which falls between being a diagnostic study and being an attempt to elicit an efficacious 
result. 
Dr. Parkman said that for a Phase I study to be instituted there must be adequate 
preclinical information to prove that the basic concept is valid. There must be some 
reason to believe an efficacious outcome will occur as a result of the protocol in order to 
justify undertaking a study of safety and toxicity in a Phase I trial. Therefore efficacy is 
not really of tertiary concern, but must be viewed as a primary concern, even in a Phase 
I trial. 
Dr. Childress agreed with Dr. Parkman and said that if there were no theoretical or 
experimental basis for thinking a therapy could work, there would be no interest in 
questions of safety about that therapy. 
Dr. Zallen asked the following four questions relative to biopsies of tumor or tissue: 
1. How many biopsies will be taken from each patient? 
2. Will the patient submit or sign a separate consent form for each biopsy? 
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Recombinant DNA Research, Volume 14 
