Recombinant DNA Advisory Committee - 03/1-2/93 
Dr. Carmen asked the investigators how they would have responded to the question 
about transduction efficiency as listed on the Cover Sheet for Expedited Review. Dr. 
Sobol responded that the percentage of cells transduced is not an important issue; the 
key factor is the amount of IL-2 that is expressed. Ms. Grossman said that if an 
investigator cannot demonstrate reliable and efficient transduction of cells, then the 
protocol should not be approved. Dr. Royston asked, "If we have a selected cell line that 
is transduced and secreting the gene product, what is the concern?" Ms. Grossman said 
that the basic issue is that the RAC must be certain that investigators are capable of 
transducing genes into target cells. Dr. Sobol agreed that gene expression by the target 
cell must be demonstrated; however, the efficiency of the transduction should not be a 
decisive factor. 
Dr. Sobol said that the first time any agent is administered to a human subject, the 
effects of a particular dosage are unknown. Only by monitoring the patient's response 
can the appropriate dose can be defined. Deferring approval of a study in which the 
only way to obtain data is in the human subject suggests that the RAC is too focused on 
details. Dr. Leventhal stated that Dr. Sobol's comments confirm her opinion that this 
protocol should not have been approved. To approve any protocol, there must be an 
assurance that every patient who participates in an experiment, including novel therapy, 
will provide valuable data about that therapy. Investigators cannot discover efficacy in 
the course of treating a single patient. The fact that the investigators have no plan to 
study other patients confirms that no valuable information will be gained. Dr. Royston 
stated that they would be evaluating the patient's immune response to this treatment. 
Dr. Leventhal said that if the study had been presented as the first of a series of patients, 
she would have recommended approval of this single patient protocol. In that way, 
valuable scientific information could have been derived from the experiment. Dr. 
Royston responded that he would like to obtain approval for the treatment of additional 
patients; however, the FDA required that this request to be submitted as a single patient 
IND. Dr. Leventhal said that the RAC will certainly review single patient protocols; 
however, this protocol is inadequate. 
Dr. Royston stated that he is concerned by the fact that if he had submitted this study as 
a single patient protocol through the normal RAC review process, that it probably would 
have been deferred by the committee. Dr. Sobol said that he shares Dr. Royston's 
perspective. Dr. Walters stated that the RAC would welcome the review single patient 
and multiple patient protocols submitted by Drs. Sobol and Royston in the future, and 
that the committee would attempt to be fair in its review of such protocols based on 
their merits. 
Recombinant DNA Research, Volume 17 
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