Human Gene Therapy Subcommittee - July 29-30, 1991 
Dr. Kelley asked if the value of portal injection in patients is its relative safety as 
compared to the spleen injection. Dr. Wilson replied safety was a consideration, as 
well as expertise in portal vein infusions. Dr. Kelley said that while the expected 
reduced cholesterol levels may not guarantee therapeutic efficacy, this should not 
interfere with approval of the protocol since certain modifications might render this 
treatment therapeutic. 
Dr. Erickson moved to approve the protocol with the following two stipulations: (1) 
that treatment will be limited to receptor-negative patients (the chance of obtaining 
efficacy will be greater if younger patients are used); and (2) a sequential consent form 
will be adopted. Dr. D. Miller seconded the motion. 
Dr. McGarrity said the HGTS should require some sort of quality assurance testing. In 
the case of the hepatocytes, they are only in culture for three days. By the time results 
are available, they are only of retrospective value. Quality assurance tests should be 
performed on the packaging cell line as well as on the hepatocytes. Controlled studies 
should be performed to evaluate for spontaneous transformation in cultures of 
nontransfected hepatocytes, hepatocytes with the vector alone, and hepatocytes with the 
vector plus the LDL gene. 
Dr. Leventhal suggested a separate consent form for the liver resection which states 
that the patient will be notified if the cells have been successfully transfected. At this 
point reintroduction becomes possible. A separate consent form should be added to 
cover that eventuality, as well as liver biopsies and possible post-mortems. In this way, 
the patient is informed that the cells will not be reintroduced if they have not been 
transfected. It also allows the risks associated with the two procedures to be discussed 
separately. 
Dr. Parkman said that patients usually sign the consent form for the reinfusion and the 
consent form for the resection at the same time. If you wait until the cells have been 
prepared, there would be a tremendous amount of pressure on the patient to consent. 
Ms. Meyers argued against the sequential informed consent. If a patient is to 
participate in an experiment, the patient should know up front what is expected down 
the line, including follow-up analysis. A sentence could be added to the informed 
consent to state that there is a possibility that the cells may not be reintroduced. 
Dr. Parkman proposed two amendments: (1) Additional information must be provided 
about the vector and the quality control assays performed on the vector preparation. 
(2) Quality control assays must be performed on the transduced hepatocytes, with the 
understanding that the information will not be available before the cells are 
reintroduced. This quality control mechanism needs to be defined indicating what tests 
will be performed, how many dry runs will be performed, and how adverse reactions 
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Recombinant DNA Research, Volume 14 
