Recombinant DNA Advisory Committee - 2/10-11/92 
Form A asks for a copy of the latest version of the protocol plus a collation of all the 
changes that occurred since the RAC review and a description of the proposed quality 
control measures. 
Form B asks if there have been any significant amendments to the protocol, adverse 
reactions reported, and measures of gene transfer success in vitro and in vivo. In measures 
of gene transfer success in vitro, is the investigator able to transduce the material as 
anticipated in preparing the materials? Have the investigators had any unexpected results 
in ongoing quality control measures? Are there any unanticipated problems? In the 
measure of gene transfer in vivo, has there been any evidence of activity of the transferred 
gene in the patients treated? Has the patient's condition improved? If negative effects 
resulted, has there been any evidence of adventitial spread of transduced material? Was 
any tumor/normal tissue obtained after transduced material was administered? Was there 
a post mortem if the patient died? Was there any sign of gonadal transfer of genetic 
material and by what criteria? Is there any evidence of generation of replication- 
competent virus related to the gene transfer procedure in patients? What toxicity was 
seen, either local or systemic? Is there any evidence of deterioration of disease state that 
could be related to the gene transfer procedure, or any evidence of effects on other genes? 
Are there problems that have occurred that were not anticipated prior to starting the 
protocol? 
Form B asks for patient accrual data by requesting the number of patients considered and 
unable to be included in the protocol. Dr. H. Miller of the FDA commented previously 
that these last two questions were unreasonable because safety and efficacy issues are not 
addressed. Because Dr. H. Miller has concerns about asking for this information, perhaps 
these two questions should be omitted. The form then asks how many patients have 
actually been entered in the study, and for a list of the patients indicating on-study dates, 
off-study dates, and the reason for being taken off-study, and an indication of the number 
of patients that have died and their cause of death. What was the number of those whose 
participation was completed as planned? Are the patient accrual goals being met in a 
timely fashion; if not, why not, probably covers those first two questions. In other words, if 
10 patients are to be treated in a year but only one patient has been treated in two years, 
is it because there are not enough patients or because the procedures are unsuccessful. 
These two questions could be deleted. Have any publications resulted from this protocol? 
If so, provide reprints. 
Dr. Leventhal said Dr. H. Miller reported that the FDA requires annual reports; therefore, 
RAC does not need to ask for additional information. However, the FDA will not release 
this information to the RAC. There is a fair amount of overlap between what the FDA 
requests and what the RAC will request in patient accrual and the overall adverse 
reactions. RAC will need more detailed information about gene transfer than what might 
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Recombinant DNA Research, Volume 15 
