June 1, 1990, Human Gene Therapy Subconmittee Minutes 
Dr. Walters then called on Dr. Childress for his comments on the protocol. Dr. 
Childress said after having some concern that the protocol was aimed at a "moving 
target," he felt the investigators had done a good job in developing their latest response 
in relation to the "Points to Consider," and that the material they had provided was 
helpful in allaying some concerns in this regard. However, he said this did not minimize 
the concerns raised over the scientific and technical bases for the concern about risk- 
benefit. 
Dr. Childress said that the risk involved in this protocol was not "minimal risk," and he 
was glad to have heard that the NIH IRB had in fact approved this as research involving 
"greater than minimal risk." However, he felt that if the risks were greater than minimal, 
the benefits should also be greater than minimal. Therefore, they should be greater than 
those anticipated from alternative therapy with either bone marrow transplantation or 
PEG-ADA therapy. This indeed would require careful selection of a subset of patients 
in whom this would be the case. He was happy to see part three of the protocol had 
been withdrawn because he had some concern about withdrawing PEG-ADA therapy. 
In terms of alternative treatments and patient selection, there was still uncertainty as to 
where these treatments stand relative to risk and benefit. Further, he had concern over 
the points raised about the subjective criteria used for patients and physicians for 
including patients in the study. He said there were two questions to address: (1) Are 
there objective criteria that have been laid out that narrow the pool of prospective 
patients? (2) Are there objective criteria that would bring subjects into the study? 
Dr. Childress asked what incentive parents might have for enrolling their children in the 
study, and asked if having the cost of PEG-ADA and gene therapy covered might be an 
undue inducement, rather than having a strong medical reason, for enrolling a child in 
the study. He said he would be interested in how the parents would be informed of the 
risks and benefits and again stressed the importance of fully disclosing these issues so 
that parents can make an informed judgment on enrollment. 
Dr. Walters thanked the primary and secondary reviewers and opened the floor for 
discussion. Dr. Kelley said that two questions are critical. Can the experiment work? 
Can it be determined if it's working? He said that one factor in this was the half-life of 
the implanted cells, particularly without IL-2 or some other growth factor that would 
lead them to proliferate. He said he expected much of this data to come out of the 
N2/TIL study but that he had not seen it to date. He said it was necessary to have some 
kind of estimate of the level of ADA activity within a cell or extracellular fluid which 
would be needed to assure detoxification of the deoxyadenosine metabolites. 
Dr. Kelley said to answer the question of whether one can determine if this therapy is 
working is complicated by the presence of PEG-ADA. He said it would be better if a 
"crisper definition" of this assessment had been made. 
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