Recombinant DNA Advisory Committee- 9/12-13/94 
Dr. Isner said that the severe narcotic dependent pain experienced by the PAD patients is 
unlikely to be relieved by a placebo effect. For those patients, pain relief is a reliable 
endpoint. Dr. Motulsky accepted this explanation. 
Dr. Motulsky asked if the need for a control group in the study has been seriously 
considered. Dr. Isner replied affirmatively. The question was deliberated in the initial 
design of the protocol, and later in IRB and IBC reviews. It was deemed unconscionable 
to enroll patients who have 4 weeks of narcotic dependent pain, 4 weeks of ulcers, and 
marginal circulation to a sham transfection by balloon angioplasty. The risk of this 
procedure is higher in these patients, and the risk is not worth taking in a patient who 
stands to gain no benefit from that kind of intervention. 
In response to the question of whether or not the protocol is a Phase I study, Dr. Isner 
said that safety is the principal objective of this initial study, but it does not seem wise to 
exclude the possibility to discover a potential benefit. Mr. Capron commented that from 
the small number of patients involved in this study, it is not possible to definitively address 
the question of efficacy. A control study group is needed in a study designed to show 
efficacy. But in this initial study, the decision not to include a control group of patients 
seems to be reasonable. Dr. Parkman commented that it is good science to have a control 
group, but the idea of using the patients as their own control is the only appropriate thing 
to do at this time. 
Committee Motion 
Dr. Parkman made a motion to approve the protocol with stipulations to require 
ophthalmological examination including funduscopic photography and a revised Informed 
Consent document to include a pain scale and medical diary. Dr. Miller added a friendly 
amendment to require the use of the original plasmid vector. Dr. Motulsky seconded the 
motion. 
Ms. Meyers noted that there is no commercial sponsor involved in this study. Dr. Miller 
said that it is very inexpensive to produce a plasmid DNA vector and thus there is less 
need for a commercial sponsor. Dr. Motulsky was pleased that the protocol did not have 
the problems associated with retroviral vectors. 
The RAC approved a motion made by Dr. Parkman and seconded by Dr. Motulsky to 
accept the protocol submitted by Drs. Jeffrey M. Isner and Kenneth Walsh of St. 
Elizabeth’s Medical Center at Tufts University by a vote of 15 in favor, 0 opposed, and no 
abstentions. RAC approval is contingent on review and approval of the following 
stipulations by the primary RAC reviewers: (1) revision of the appropriate sections of the 
protocol to clarify that the phVEGF165 vector will be the only vector used for the human 
study (the same vector used for the preclinical animal studies); (2) submission of a 
revised protocol and Informed Consent document that includes a statement that patients 
will undergo complete ophthalmologic examination (including funduscopic photography) 
prior to, during, and following vector administration; and (3) changes in the Informed 
Consent document as suggested by the RAC members, e.g., quantification of pain scale, 
Recombinant DNA Research, Volume 20 
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