Recombinant DNA Advisory Committee - 12/1-2/94 
Dr. Walters stated that the RAC Data Management Report system monitors the results of RAC and NIH 
approved human gene transfer protocols, particularly adverse events and patient accrual. This semiannual 
reporting system was first initiated by the late Dr. Brigid Leventhal. Dr. Walters thanked members of the 
working group and Ms. Debra Wilson of the ORDA for their expanding efforts to collect, categorize, and 
review this substantial quantity of information. Dr. Walters called on Dr. Smith, Chair of the Working Group 
on Data Management, to present the December 1994 Data Management Report. 
Dr. Smith stated that due to the increasing volume of information that is being submitted by investigators, the 
protocols have been subdivided into categories. Each category was reviewed by one or more members of the 
working group. Dr. Smith thanked Dr. Ross for providing a comprehensive written critique of all studies prior 
to the meeting. This timely critique allowed Ms. Wilson to contact investigators for follow-up information. 
Working group assignments were as follows: (1) All human gene transfer protocols -- Drs. Smith, Ross, and 
Noguchi; (2) Gene Therapy/Cancer/Non-Vaccines - Drs. Smith and Samulski; (3) Gene 
Therapy/Cancer/Vaccines -- Drs. Erickson and Samulski; (4) Gene Therapy/HIV — Dr. Straus; (5) Gene 
Therapy/Inherited Genetic Disorders -- Dr. Motulsky; and (6) Gene Marking -- Dr. Parkman. 
Dr. Smith noted the Data Management Report which summarizes the individual reports submitted by 
investigators (see Attachment IV-Data Management Report). 
Dr. Smith stated a total of 329 subjects have been treated on the 91 RAC-approved protocols. Fourteen 
protocols are currently closed and 2 protocols are currently placed on hold either by FDA or by the 
investigators. A total of 36 academic institutions are participating in the 91 RAC-approved studies. Several 
issues should be considered by the RAC: (1) Protocols involving the GITkSvNa and GlTklSvNa retrovirus 
vectors have been associated with numerous toxicides. (2) A total of 103 deaths have been reported; however, 
only 7 autopsies were reported by investigators. A 5% autopsy rate is extremely low. Important informadon 
related to gene transfer such as transmission to sites other than target tissues has not been obtained from 
autopsy specimens. (3) Several investigators have failed to enroll any padents on their NIH-approved studies 
or have failed to enroll any padents for more than one year. (4) There appears to be some confusion 
regarding the approvals that are required prior to inidating these studies, e.g., all 3 of the Viagene sponsored 
studies were initiated prior to the NIH-Director’s approval. To be in compliance with the NIH Guidelines , any 
investigator who receives NIH funding or collaborates with an investigator at an insdtudon that has receives 
NIH funding must receive NIH approval to inidate human gene transfer protocols. (5) Biological efficacy is 
difficult to determine for some studies. Although the results observed in Dr. Blaese’s protocol (#9007-002) on 
severe combined immunodeficiency (SCID) due to ADA deficiency are promising, the efficacy data is 
complicated by the fact that all of the subjects are concurrently on polyethylene glycol (PEG)-ADA enzyme 
replacement therapy. 
Ms. Meyers was concerned over the poor autopsy rate. The RAC has made great efforts to ensure that 
investigators include the autopsy request statement in the Informed Consent documents; frequently such 
requests have been overlooked by investigators. Potendal scientific informadon is lost forever due to the lack 
of proper autopsy. This negligent situadon must be corrected. 
Dr. Parkman commented that it is less of a concern to insist on a statement in the Informed Consent 
document to request autopsy than to require it. After a protracted illness of most padents, the family 
members may choose not to have autopsy performed on their deceased relatives. Dr. Parkman noted that 
most padents who died in gene transfer studies are those who died from advanced cancers in the gene marking 
protocols; persistence of genetically marked cells are not expected in these padents. Ms. Meyers’ argument 
has much greater significance if patients are involved in gene therapy protocols where persistence of the 
transferred gene is expected. 
Dr. Zallen expressed concern about the lack of pertinent informadon derived from the autopsy results, e.g., 
presence of replication competent viruses or gene transfer to sites other than the target tissue. Dr. Secundy 
asked if the autopsy rate for gene therapy protocols is different from the rate for gene marking studies. Clear 
Recombinant DNA Research, Volume 20 
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