Human Gene Therapy Subcommittee - 11/21-22/91 
Ms. Meyers asked if the stipulation could be added that a sentence be inserted in the 
informed consent document that states that there will be no cost to the patient resulting 
from complications of the study. Dr. Parkman said that the HGTS had no authority to 
make this request of Dr. Cometta. Ms. Areen reminded the HGTS members that this 
issue should be forwarded to Dr. Healy for consideration. Dr. Leventhal suggested that 
Dr. Cometta should consult with the Indiana University IRB and revise the wording in 
the informed consent document to be as generous to the patient as possible in terms of 
the risks of the gene therapy portion of the protocol. 
Dr. B. Murray inquired if the compensation problem arises from the hospital and not 
from Dr. Cometta's physician fees. Dr. Leventhal replied that physician fees are not the 
problem; the hospital does not want to provide compensation for any research-related 
injuries. Dr. Cometta stated that Indiana University has never compensated for 
research-related injuries and that providing compensation for injuries resulting from this 
gene therapy protocol would set a precedent for the institution as it would for most other 
institutions in the U.S. Dr. Cometta added that to withhold approval because of this 
issue would be unfair and inconsistent with previous decisions made by the HGTS. 
Dr. Epstein explained that if marked cells are detected in all 10 patients, then the 
marrow is clearly contributing to relapse. Conversely, if no marked cells are detected, 
then the marrow is not suspect. He inquired as to how the data would be interpreted if 
the number of patients with marked cells falls between these extremes. Dr. Cornetta 
said that if marked cells are detected in even a few patients, marrow cells are still 
indicated as contributing to relapse. Dr. Cometta added that valuable information will 
be obtained regarding the benefit of purging. 
Dr. Epstein inquired as to the number of positive patients that would be required before 
purging techniques would be reconsidered. Dr. Cometta replied that 3 positive patients 
out of 5 would be statistically significant enough that he would ask the IRB to reconsider 
purging in these bone marrow transplant patients. Dr. Leventhal said that the protocol 
should have included a statistical section that addresses the endpoint, e.g., the number of 
labeled relapses that would be statistically significant. Dr. Leventhal said that she would 
like to have this included as a stipulation for approval of Dr. Cornetta's protocol. She 
added that a mathematical model should be included that addresses itself to the 
question. If 5% of the cells are transduced in one patient, how many cells are 
contributing to relapse? How will the statistics change if positive cells are observed in 5 
patients, 7 patients, etc.? The transduction percentage on each patient, the number of 
patients relapsing, and the time of detection will have to be taken into consideration. 
This formula will be complicated. Dr. Epstein added that a stopping rule should be 
included that, if marrow cell labeling is demonstrated in 3 patients, the study will be 
terminated. 
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