Recombinant DNA Advisory Committee - 3/3-4/94 
significant safety issues of concern. Statistical analysis of this study could be improved if 
the number of treatment groups is reduced and the number of subjects per group is 
increased. The study should be limited to autologous cells with 3 dose-escalation groups 
and 6 patients per dose. The investigators responded that the allogeneic group is 
necessary because autologous cells may be difficult to obtain from all patients and this 
disease is very rare. The investigators proposed an alternative design involving 2 dose 
escalation groups: 3 patients in the low dose group and 6 patients in the high dose 
group. The Informed Consent document does not stipulate that the sponsoring 
institution will provide compensation for non-negligent injuries arising from participation 
in the protocol. The assent form language is not understandable to children. Dr. Chase 
recommended that the term "vaccine" should be deleted from the Informed Consent 
document since this protocol is a Phase I study. 
Review-Ms. Meyers (presented by Dr. Smith) 
Ms. Meyers' written comments raised several concerns regarding the Informed Consent 
document. She reiterated Dr. Chase's comments about the children's assent form, the 
use of the term "vaccine," and language relating to the provision of medical care if 
individuals are injured during the course of their participation in the protocol. An 
explanation of long-term follow-up was not included. The investigators' written 
comments noted that the Informed Consent document language is in accordance with the 
IRB's policy. Since there is the possibility of benefit to subjects, the institution should 
not have the responsibility of funding treatment for non-negligent complications. Ms. 
Meyers' written response to the Principal Investigators noted that a Phase I study is not 
designed to provide benefit to patients. 
Other Comments 
Dr. Zallen asked about the time frame in which patients receiving allogeneic cells would 
be informed about their eligibility to participate in the study based on HLA typing. Has 
HLA typing been completed for all of the cell lines in the cell bank? In regard to the 
Informed Consent document, the investigators should explain the statement that subjects 
will be responsible for all costs except for the experimental "vaccine" itself. Dr. Smith 
added that there is the potential for long-term survival of participants in this study; 
therefore, long-term care is a pertinent issue. 
In response to the RACs discussion regarding the issue of compensation for research 
related injuries. Dr. Wivel (Executive Secretary) referred to a letter dated January 28, 
1994, from Mr. Robert B. Lanman, NIH Legal Advisor. Mr. Lanman stated that 45 
Code of Federal Regulations Section 46.116(a)(6) governs the use of human subjects in 
research conducted or supported by the Department of Health and Human Services 
(DHHS). These regulations require that when research involving more than minimal 
risk is proposed, the subjects of the research must be provided with an explanation as to 
whether any compensation or any medical treatments are available if injury occurs, what 
such compensation consists of, and where further information may be obtained. Thus, 
the RACs recommendations relating to research-related medical compensation is 
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