Recombinant DNA Advisory Committee - 03/1-2/93 
Dr. Royston stated that if the RAC retrospectively disapproved the protocol, there would 
be a greater understanding as to the perceived defects of the study. The RAC has 
already articulated their expectation that efficacy should be demonstrated in an animal 
model. There is disagreement about this particular requirement in the medical 
community. Also, there is disagreement about the extent of preclinical data that is 
required for a single patient expedited review protocol. Ms. Meyers reminded Dr. 
Royston that the RAC is not voting on this protocol; approval has already been granted 
by the NIH Director. Dr. Royston encouraged the RAC to retrospectively vote on this 
protocol to determine whether the committee's decision would have been the same as 
the NIH Director's decision. Ms. Grossman reminded Dr. Royston that the 
documentation submitted to the RAC is incomplete; therefore, it is impossible for the 
committee to make an informed decision. The purpose of this discussion is for the RAC, 
not the investigators. 
Dr. Sobol stated that he would be unable to satisfy all of the criteria listed on the Cover 
Sheet for Expedited Review , even with the data that is currently available. There is no 
preclinical efficacy data, only historical data. Would the RAC have considered historical 
data in human subjects who were immunized with glioblastoma cells as an acceptable 
alternative to preclinical efficacy data? This proposal was based on data from a single 
uncontrolled study suggesting a survival benefit to patients who received adoptive 
immunotherapy of glioblastoma cells. The rationale is that gene transfer to these 
adoptively transferred tumor cells should enhance the survival benefit. There is no 
evidence that these procedures should produce any toxic side effects. 
Dr. Parkman said that the fact that 1 cytokine gene has proven effective in the regression 
of 1 particular type of tumor does not establish preclinical efficacy for another cytokine 
or another tumor type. Dr. Sobol disagreed with Dr. Parkman's statement. Dr. Post 
noted that the uncontrolled study referenced by Dr. Sobol was reported a long time ago. 
Have any controlled follow-up studies been published since the original report? Dr. 
Sobol said that subsequent trials have been performed in which efficacy was not 
demonstrated. 
Dr. Straus said that the urgency of illness sometimes necessitates that clinicians extend 
beyond the reach of existing scientific data. There are circumstances in which protocols 
could be justified without having demonstrated efficacy in an animal model. However, 
Phase I trials of this nature usually include therapies for which there is extensive data 
about the characteristics and safety of these therapies. Gene therapy is a novel 
therapeutic approach. Until such time that there is confidence in this area of research, it 
would be inappropriate to presume that protocols should be approved that go beyond the 
boundary of existing data. Dr. Sobol disagreed with Dr. Straus. Dr. Sobol stated that he 
does not see any distinction between what is considered acceptable for chemotherapeutic 
agents versus gene transfer. 
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Recombinant DNA Research, Volume 17 
