Recombinant DNA Advisory Committee - 06/7-8/93 
possible adverse effects were reported. In one protocol, the patient's transplanted bone 
marrow failed to engraft; and in the other, a patient developed asymptomatic gliosis of 
the brain following treatment. It is unclear whether these two effects are related to gene 
transfer. Several patient deaths were reported; however, most of them were related to 
advanced cancer or complications arising from other clinical procedures. There is no 
evidence that any deaths have been directly related to the gene transfer procedures. 
Overall, the record on patient safety is reasonable. 
Ms. Meyers raised two questions: (1) Why have fewer patients been accrued in these 
protocols than were approved by the RAC? (2) Why are there more patient deaths in 
the cancer protocols than the other studies? Dr. Leventhal explained that most of the 
protocols have been recently approved and are still open, which accounts for the 
apparent low accrual rate. Dr. Geiduschek suggested that the RAC consider 
implementing an expiration date for the protocol if no patients have been treated after a 
specified period of time. Regarding efficacy, Dr. Leventhal explained that most of the 
cancer protocols are Phase I trials for patients with large tumor burdens; therefore, 
demonstration of treatment efficacy is not expected. The report also specifically omitted 
the efficacy question based on the fact that full disclosure of research data might infringe 
on the ability of investigators to publish their results in peer-reviewed journals. Dr. 
Walters concurred with this policy. Dr. Parkman added that an interim statement of 
efficacy on a small number of patients is not statistically significant. The question of 
efficacy can be addressed in the renewal applications based on data from previous trials. 
In future data reports, published efficacy results will be included. Dr. Anderson stated 
that the June 1993 Data Management Report would be published in the journal Human 
Gene Therapy. 
MINOR MODIFICATIONS TO NIH-APPROVED HUMAN GENE TRANSFER 
PROTOCOLS 
Dr. Walters summarized the minor modifications that have been approved to NIH- 
approved human gene transfer protocols. A total of 13 minor modifications have been 
approved, and are summarized in the form of a table (Attachment III). In response to 
Ms. Grossman's question on the requirements for a minor modification. Dr. Walters 
explained that a minor modification is a change that does not significantly alter the 
design of a protocol and that does not increase risk to the patient. A minor modification 
must be approved by the Institutional Biosafety Committee (IBC), Institutional Review 
Board (IRB), and the Chair of the RAC (in consultation with other RAC members as 
necessary). 
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