July 30, 1990, Human Gene Therapy Subcomnittee 
related to concern over how children would tolerate repeated i.v. infusions. He was 
concerned that if the treatment appeared beneficial, but was resulting in systemic 
reactions, he wanted to leave the i.p. administration as an option without having the 
protocol stopped while seeking approval of i.p. administration. He asked if there were 
any way to get an expedited approval from the RAC and the subcommittee to allow the 
local committees to view this as a clinical care decision. 
Dr. McGarrity said there was an agenda item that would be coming before the RAC on 
expedited review of minor modifications to protocols. 
Dr. Walters asked if other pediatricians would have comments on the i.p. route of 
administration. Dr. Leventhal said one concern relates to dealing with children who are 
sick and who probably will have an indwelling catheter in place. Subjecting their 
immune system to another foreign body would be a safety risk. She said she would 
delegate her vote on this issue to the primary and secondary reviewers, but she felt issues 
of safety must be taken into account as well as the molecular biologic aspects of the 
procedure. 
Dr. Herschfield noted that line sepsis had been seen in two patients on PEG-ADA 
therapy who had central venous lines in place for administration of immunoglobulin. He 
said the protocol did not call for children to show clinical deterioration on PEG-ADA. 
Therefore, he felt the prospective patients would not have had serious infection due to 
PEG-ADA and that a central venous line would not present any additional risk to the 
patients. 
Dr. R. Murray raised the distinction between patient management issues and issues 
related to human gene therapy. He said if this problem were deemed a patient 
management issue, then the IRB or the clinical service should be concerned about such 
matters. If, however, this was a complication produced by the use of gene therapy, this 
should be an issue for the subcommittee. He said he did not feel this was a gene 
therapy issue as far as the introduction of a central venous line was concerned and that 
he would be comfortable with allowing the chairman to approve such as a minor 
modification, if indeed the RAC approves this procedure of dealing with minor 
modifications. 
Dr. Parkman said he did not wish to prejudge whether such a modification should be 
viewed as "minor," but agreed that the investigators could submit it for consideration as 
such and let it be judged by the chairmen of the HGTS and the RAC. 
Dr. Leventhal moved that: 
"Institution of intraperitoneal therapy be considered a minor modification 
which could be reviewed by the chairs and considered by the chairs as to 
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