Human Gene Therapy Subcommittee - 11/21-22/91 
there is a subset of investigators who incorporate minor changes as the trial continues. 
Any changes that have occurred since the final approval of the protocol can only be 
noted if the investigator has submitted a formal amendment to the protocol. Dr. Wivel 
reported that one investigator has already requested a change in an approved protocol in 
the form of a minor amendment. This amendment was actually reviewed and approved 
by the HGTS. A second minor amendment is pending HGTS review. 
Dr. Miller asked for clarification regarding the question, "What in vitro evidence is there 
for the efficiency of genetic manipulation?" Dr. Leventhal responded that this question 
addresses the efficiency of gene transfer in the material that is going to be administered. 
Perhaps the questions should be shortened. Dr. Parkman agreed with Dr. Leventhal and 
stated that if investigators answered every question on the reporting form as it appears 
now, too much paperwork would be submitted and the questions would not be addressed 
specifically and concisely, particularly if the HGTS requires the investigator to complete 
this form for every patient who is treated. 
Dr. Miller said that it will be important that investigators understand that it will not be 
sufficient for them to respond that their transduction efficiency met their expectations. 
Actual data should be submitted regarding the percent transduction. Dr. Neiman stated 
that the question regarding quality control measures is too broad and should be 
reworded. 
Dr. Neiman said that another important issue is: Who will be responsible for monitoring 
these reports. The original primary reviewers? It is important that the person examining 
the data have knowledge of the protocol. Dr. Leventhal stated that it is important that 
the reviewers have access to data regarding adverse reactions. Dr. Miller inquired as to 
whether the HGTS has a mechanism for addressing adverse reactions. Will investigators 
be allowed to continue with their protocols? Can the RAC withdraw its approval? Ms. 
Meyers stated there is currently no mechanism to deal with this issue. Dr. Wivel 
explained that in the broadest sense adverse reactions could be considered a violation. 
The RAC would have to evaluate a particular incident and decide whether it requires 
further investigation. The machinery is in place, and it would be a judgement call for 
the primary reviewers in concert with the RAC to suggest the appropriate action. 
Ms. Meyers stated that there is currently a database and registry for patients undergoing 
gene therapy. Are RAC approved investigators reporting to this registry? Will the 
information gathered from this proposed report form duplicate data that already exists? 
Dr. Anderson said that the registry has been proposed by Dr. Fred Ledley; however, it 
has not been started because Dr. Ledley is still trying to secure funding. Ms. Meyers 
asked if there was an official patient registry. Dr. Anderson answered that no official 
registry exists. Ms. Meyers asked: If the registry is funded at a future date, will 
investigators be required to report to the RAC as well as the registry. Dr. Leventhal 
stated said that Ms. Meyers had identified an important problem. It is unfair to require 
investigators to submit multiple reports of the same data. The question is: Who will be 
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