Human Gene Therapy Subcommittee - 7/30/90 
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 
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Recombinant DNA Research, Volume 14 
