Recombinant DNA Advisory Committee - 12/1-2/94 
revise the Informed Consent document. 
Dr. Walters noted that the immunity involves both the humoral and cellular immune responses. Dr. Par km an 
explained that the immunized animal study is to address two issues: (1) how much less infection in the 
preimmunized animals, and (2) how much more toxicity in these animals. The stipulated immunized cotton rat 
experiment will address these two issues. 
Dr. Finkle said if the RAC approves the clinical part of the Phase I study, the investigators will perform the 
animal studies on safety to meet all the RAC stipulations. Dr. Ross stated that there are too many 
contingencies to approve this protocol; it should be deferred until more information is provided. 
Mr. Capron asked how much time is needed to complete the safety study. Dr. Finkle said the rat experiment 
can be completed shortly, and the primate study will take several months. Dr. Wivel said the deadline for 
protocol submission for the March RAC meeting is January 9, 1995; if it is a deferral, the investigators have to 
meet the deadline. Ms. Meyers noted that the experiments will take time to complete; therefore, there is no 
rush for approval Dr. Finlde stated it is extremely important to know that the investigators are moving 
forward on the right track, and a positive opinion of the RAC is cruciaL Drs. Miller and Parkman explained 
that deferral is not disapproval; the concept of the proposal is acceptable, but the safety data is inadequate. 
Mr. Capron asked if the immunized rat experiment will provide definitive information. Dr. Parkman 
responded affirmatively. Mr. Capron and Dr. Erickson asked if a subcommittee could review such data; 
therefore, the RAC could approve the protocol with contingencies; however, if there is toxicity in the rat 
experiment, the protocol should not go forward. 
Dr. Secundy stated that she would not vote for approval of this protocol since the investigators did not provide 
the required materials outlined in the Points to Consider. A consistent standard should be held for all protocol 
submissions. Dr. Parkman said the proposal does include toxicity data; however, additional toxicity data is 
requested to assure its safety. Dr. Smith said that the requested information is important enough to require 
the full RAC review. Responding to Dr. Secimd/s remark regarding submitted materials. Dr. Venook said all 
the Points to Consider questions have been addressed in the present proposaL Dr. Parkman reiterated his 
conclusion that if the animal data are safe, the protocol could be approved by a subcommittee; if there is 
positive toxicity, it will be forwarded to the full RAC for review. He favored a conditional approval. 
Dr. Walters called the motion. The motion is to defer approval of the protocol pending submission of 
additional data about toxicity and transduction efficiency in preimmunized cotton rats, data about germ line 
integration, p53 mutations, and a detailed autopsy plan. He noted that the stipulation does not require the 
monkey data. 
The RAC disapproved a motion made by Ms. Meyers and seconded by Dr. Secundy to defer the protocol 
submitted by Drs. Alan Venook and Robert Warren by a vote of 8 in favor, 9 opposed, and no abstentions. 
The motion to defer the protocol failed. 
Committee Motion 2 
A second motion was made by Mr. Capron to approve the protocol with previously described contingencies. 
The motion to approve the protocol was seconded by Dr. Erickson. 
Dr. Chase stated that he was concerned with the lack of critical information presented in this protocoL There 
are 3 categories of protocols: (1) the type with no problem, (2) the totally unacceptable type that should not 
have been brought to the RAC, and (3) the most time-consuming type like the present protocol. He suspected 
some investigators have a strategy of submitting a protocol with just enough supporting data to obtain a 
contingent approval. He was not sympathetic to the strategy, but he recognized a legitimate need for it. Dr. 
Chase stated that he would vote for approval of the protocol. In the future, the technical points should be 
resolved by a subcommittee rather than by a time consuming discussion at the full RAC meeting. 
Recombinant DNA Research, Volume 20 
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