Human Gene Therapy Subcommittee - 11/30/90 
Factor (TNF). The FDA had concerns that the study would be performed in a more 
classical Phase I study progressing to a Phase II study, rather than mixing certain 
elements of toxicity/dose-escalation with therapeutic efficacy. He said he 
understood the FDA had approved a modified protocol. 
Dr. Anderson said that the FDA had made three changes to the protocol concerning 
safety. These were to: (1) begin the study with a dose escalation less than once 
every three weeks, (2) have an intermediate dose of interleukin-2 (IL-2) when the 
dose is escalated, and (3) not administer ID2 initially. 
Dr. Anderson said that all the conditions set by the HGTS and the Recombinant 
DNA Advisory Committee (RAC) were unchanged. Dr. Parkman noted that the 
HGTS and the RAC had only approved a Phase I trial and would expect that the 
investigators would return with the Phase I data before proceeding to Phase II. Dr. 
Anderson said that it was his intention to return with this data. 
III. ADDITION TO THE POINTS TO CONSIDER DOCUMENT TO EXPEDITE 
MINOR MODIFICATIONS ON APPROVED PROTOCOLS 
Dr. Walters said that the RAC had approved a procedure for expedited review that 
was developed by a subgroup of the RAC chaired by Ms. Areen. Dr. Walters noted 
that the text of the procedure reads as follows: 
"A minor change in protocols approved by the HGTS and the RAC is a 
change that does not significantly alter the basic design of a protocol 
and that does not increase risk to the subjects. If the change has been 
approved by the relevant Institutional Review Board (IRB) and 
Institutional Biosafety Committee (IBC) and the Chair of the HGTS, 
the Chair of the RAC may then give approval. It is expected that the 
Chairs will consult with appropriate members of the committees. The 
Chairs will report on any such approvals at the next regularly scheduled 
meetings of the respective committees." 
Dr. Walters asked for a motion regarding this procedure for dealing with minor 
changes to approved protocols. Dr. Mclvor moved for approval by the HGTS. Dr. 
Parkman seconded the motion. There being no discussion. Dr. Walters put the 
motion to a vote. The motion passed unanimously by a vote of 10 in favor, 0 
opposed, and no abstentions. 
IV. PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES 
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