Recombinant DNA Advisory Committee - 12/1-2/94 
informed that all specimens should be cryopreserved not fixed in formalin. Additional autopsy information is 
unavailable because the majority of the families would not consent to autopsy. 
Dr. Noguchi commented that FDA is concerned about the adverse effects, particularly infections relating to 
either insertion of the Ommaya reservoir or that have been associated with the GTI GlTklSv.Na vector. This 
protocol is a multicenter study, and the FDA is cautious about treating more patients, especially children. 
Dr. Miller was concerned about the inference of efficacy by GTI for this Phase I study since there is no 
control group and the comparison to the historical data may be biased due to selective patient enrollment. Dr. 
Berger said that a formal Phase III study is required to answer the question of efficacy. Dr. Marcus 
commented that it is very difficult to conduct randomized control trials for fatal diseases. Dr. Berger noted a 
precedent in which the FDA approved a drug based on an expanded Phase II study since the drug was found 
that a definite prolongation of survival over a matched historical control. Dr. Chase was concerned about a 
scenario in which a drug could become a standard therapy although it had never undergone thorough 
evaluation of efficacy. 
V-C. FUTURE DIRECTIONS OF DATA MANAGEMENT REPORT-DRS. NOGUCHI AND SMITH 
Dr. Walters called on Drs. Smith and Noguchi to provide an update on Data Management of human gene 
transfer protocols. Dr. Noguchi explained that public RAC discussion of the semiannual Data Management 
Reports serves a critical function. Public discussion of this information, particularly adverse event reporting, is 
imperative to the FDA. The information accumulated by Ms. Wilson and the working group has been 
proposed as a pilot project for the FDA’s $26 million Submission Management and Review Tracking project. 
Dr. Noguchi thanked Ms. Wilson for her significant contributions to this ongoing effort. Dr. Noguchi 
recommended that the RAC forward a letter of support for this project to the FDA Commissioner. 
Committee Motion 
A motion was made by Dr. Smith and seconded by Dr. Haselkorn to send a letter (as recommended by Dr. 
Noguchi) to the FDA Commissioner. The motion passed by a vote of 17 in favor, 0 opposed, and no 
abstentions. 
Dr. Par km an recommended that each member of the working group should submit their recommended 
changes to the Data Reporting Forms to ORDA that would capture information specific for their assigned 
category. 
Mr. Capron stated that the RAC should discuss implementation of Dr. Motulsk/s recommendation regarding 
the inclusion of ad hoc experts for the review of novel protocols in which the RAC may have limited expertise. 
Mr. Capron said the key issue was whether the RAC has the foreknowledge to determine the necessity for 
such expertise. The RAC was unaware of the necessity for such review when Dr. Wilson’s familial 
hypercholesterolemia study (#9110-012) was reviewed. Dr. Motulsky said that new target diseases or novel 
applications of gene delivery may be triggers for ad hoc review. Dr. Par km an said that ad hoc experts would 
benefit protocol review in the case where an assigned reviewer does not possess adequate expertise for the 
proposed study. 
Dr. Secundy expressed concern about the low autopsy rate for all gene transfer studies to date. There must be 
increased communication between the RAC and investigators about the necessity of autopsy. Dr. Saha said 
the investigators are the ones best able to make the scientific judgment about the need for specific autopsies. 
Dr. Smith commented that the real issue is the reporting of autopsy results, not whether the autopsy was 
conducted. Dr. Anderson’s account of detailed autopsies conducted on Dr. Rosenberg’s protocol #8801-001, 
have never been reported to the RAC or published in the literature. Dr. Secundy suggested that the Points to 
Consider in the Design and Submission of Protocols for the Transfer of Recombinant DNA Molecules into the 
Genome of One or More Human Subjects ( Points to Consider) should be amended to include more specific 
Recombinant DNA Research, Volume 20 
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