Recombinant DNA Advisory Committee - 12/3-4/92 
the investigators. The protocol and the informed consent document would be more 
accurately titled, A Phase I Study of the Effects of A Single Administration of ... In 
addition, the early introductory sections of the consent form should clearly state it is 
unlikely that there will be any clinical benefit to the patient from a single administration 
of this vector. 
Dr. Walters questioned the exclusion of fertile individuals from this study. The 
background provided by the investigators explained that most male CF patients are 
infertile. What fraction of females are infertile due to their disease? While concern 
regarding unintended germ line effects is understood, if potential subjects are willing to 
commit themselves to the practice of contraception, then it is discriminatory to exclude 
individuals solely on the grounds of their fertility. The investigators need to discuss the 
possible effects of transmission of the vector to a third party bystander. Although this 
protocol is well designed, the responses to the Points to Consider in the Design and 
Submission of Protocols for the Transfer of Recombinant DNA into the Genome of Human 
Subjects ( Points to Consider ) are often inadequate. The majority of responses were 
primarily references to the protocol. All investigators should take the time to allow the 
reviewers to form an adequate conception of the protocols from reading through the 
Points to Consider. References to other sections do not provide much useful information. 
Dr. Walters said that he consulted a pulmonologist regarding this protocol. The 
pulmonologist noted the requirement for 11 bronchoscopies. Upon further examination. 
Dr. Walters documented 9 mandatory bronchoscopies and 11 optional procedures. What 
is the experimental necessity for the proposed number of bronchoscopies? The 
pulmonologist inquired whether any in vitro or in vivo studies have been performed 
regarding the effect of lidocaine on gene transduction or expression. 
Other Comments 
Dr. Post asked if the administration of 20 ml of vector to a patient's bronchus would 
cause any pain or discomfort? Could a portion of this volume be coughed up by the 
patient and subsequently swallowed? What would be the result of a CFTR enteric 
infection? 
Dr. D. Miller asked if there is any justification for the use of a negative pressure room 
for these patients? The RAC should decide on the appropriate level of containment for 
these procedures. An investigator can always increase the level of containment; an 
unnecessary precedent may be set if the RAC requires negative pressure containment. 
Dr. Leventhal agreed that the RAC must establish a minimum standard. Dr. D. Miller 
explained that negative pressure containment is an unnecessary precaution, because the 
virus is debilitated so that it cannot replicate or spread. Does CFTR present a unique 
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