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Federal Register / Vol. 58, No. 77 / Friday, April 23, 1993 / Notices 
"8. The NTH will report to the RAC 
following its internal review. 
"9. Protocols that are deferred or not 
approved by the RAC in its normal 
review process, are not eligible for 
expedited review. 
‘TO. In the development of any 
documents that are a part of this policy 
statement, the terms, compassionate use 
and compassionate treatment, will be 
deliberately avoided." 
This preliminary policy statement 
was published for comment in the 
Federal Register on February 12, 1993 
(58 FR 8500). 
During the March 1-2, 1993, meeting, 
the RAC reviewed the preliminary 
policy statement. By a vote of 16 in 
favor, 0 opposed, and no abstentions, 
the RAC recommended that the 
following section be added to the Points 
to Consider: 
"VI. Procedures to be Followed for 
Expedited Review 
“1. An investigator submitting a 
request to the NIH for expedited review 
of a gene transfer protocol must provide 
detailed information regarding the 
necessity of expedited review. 
"2. No protocol shall be considered 
without Institutional Biosafety 
Committee (IBC) and Institutional 
Review Board (IRB) approval. 
"3. At this time, all gene transfer 
protocols must be considered 
experimental. 
“4. Regardless of the method of 
review, the Points to Consider must be 
the standard of review for all gene 
transfer protocols. 
“5. Review of such protocols may 
include intramural NTH experts but 
must include extramural experts. 
"6. Among other factor to be 
considered by the reviewers, is the 
similarity of the new protocol to 
previously approved protocols. 
"7. The NIH will report to the RAC 
following expedited review and will 
include all of the materials on which the 
decision was based. The RAC will 
formally review the protocol at its next 
scheduled meeting. Patient privacy will 
be maintained. 
"8. Protocols that are deferred or not 
approved by the RAC in its normal 
review process are not eligible for 
expedited review. No protocol shall 
have more than one patient approved 
under expedited review. 
“9. As requested in the context of 
non-expedited review, none of the costs 
of the experimental protocol should be 
borne by the patient or the patient’s 
family.' 
"10. Data on all patients undergoing 
gene transfer shall be provided to the 
RAC within six months of the 
procedure." 
I accept this recommendation, and the 
Points to Consider of the NIH Guidelines 
will now contain this new addition. 
H. Amendment to the Points To 
Consider Regarding the Separation of 
the Gene Marking Informed Consent 
Document From the Therapeutic 
Informed Consent Documents 
During the September 14—15, 1992, 
RAC meeting, Dr. Leonard Post 
requested that when a gene transfer 
protocol is submitted as an addition to 
an IRB-approval clinical protocol, the 
principal investigator should submit 
two separate informed consent 
documents, one for the gene marking 
procedures and one for the therapeutic 
portion of the protocol. In the Points to 
Consider. Part I-D — Informed Consent 
(March 1, 1990, 55 FR 7446), a new 
sentence would be added to the 
introductory paragraph: 
"When gene transfer is a procedure 
separate from the therapeutic protocol, 
an informed consent document should 
be submitted for both the gene marking 
and therapeutic procedures." 
This request was published for 
comment in the Federal Register on 
February 12, 1993 (58 FR 8500). 
The request was reviewed during the 
RAC meeting on March 1-2, 1993. By a 
vote of 17 in favor, 0 opposed, and no 
abstentions, the RAC recommended that 
the following sentence be added to the 
introductory paragraph of Section I-D — 
Informed Consent: 
"When gene transfer is a procedure 
separate from a clinical protocol, 
informed consent documents should be 
submitted for both the gene transfer and 
clinical protocols." 
I accept this recommendation and the 
Points to Consider of the NIH Guidelines 
will now contain this new addition. 
II. Summary of Actions 
A. Addition of Appendix D-XXXX to 
the NIH Guidelines 
The following section is added to 
Appendix D: 
"Dr. Michael J. Welsh, Howard 
Hughes Medical Institute Research 
Laboratories, University of Iowa College 
of Medicine, Iowa City, Iowa, may 
conduct experiments on 3 cystic fibrosis 
(CF) patients £ 18 years of age with mild 
to moderate disease. This Phase I study 
will determine the: (1) in vivo safety and 
efficacy of the administration of the 
replication-deficient type 2 adenovirus 
vector, Ad2/CFTR-1, to the nasal 
epithelium; (2) efficacy in correcting the 
CF chloride transport defect in vivo; and 
(3) effect of adenovirus vector dosage on 
safety and efficacy." 
B. Addition of Appendix D-XXXX1 to 
the NIH Guidelines 
The following section is added to 
Appendix D: 
"Dr. Ronald G. Crystal. National 
institutes of Health, Bethesda, 
Maryland, may conduct experiments on 
10 cystic fibrosis (CF) patients £ 21 
years of age. Patients will receive an 
initial administration of the replication- 
deficient type 5 adenovirus vector, 
AdCFTR, to their left nares. If no 
toxicity is observed from intranasal 
administration, patients will receive a 
single administration of AdCFTR to the 
respiratory epithelium of their left large 
bronchi. Five groups of patients (2 
patients per group) will be studied 
based on increased dosage 
administration of AdCFTR. This study 
will determine the: (l) in vivo safety and 
efficacy of the administration of 
AdCFTR into the respiratory 
epithelium; (2) efficacy of thb correction 
of the biologic abnormalities of CF in 
the respiratory epithelium; (3) duration 
of the biologic correction; (4) efficacy of 
the correction of the abnormal electrical 
potential difference of the airway 
epithelial sheet; (5) clinical parameters 
relevant to the disease process; and (6) 
if humoral immunity develops against 
AdCFTR sufficient to prevent repeat 
administration." 
C. Addition of Appendix D-XXXXII of 
the NIH Guidelines 
The following section is added to 
Appendix D: 
“Dr. Kenneth Culver, Iowa Methodist 
Medical Center, Desjvloines, Iowa, and 
Dr. John Van Gilder, University of Iowa. 
Iowa City, Iowa, may conduct 
experiments on 15 patients 2 18 years of 
age with recurrent malignant primary 
brain tumors or lung, melanoma, renal 
cell carcinoma, or breast carcinoma 
brain metastases who have failed 
standard therapy for their disease. 
Patient eligibility will be limited to 
those patients who have measurable 
residual tumor immediately following 
the post-operative procedure as 
demonstrated by imaging studies. The 
number of patients treated will be 
equally divided between the Iowa 
Methodist Medical Center and the 
University of Iowa. If a positive 
response is observed in any of the first 
15 patients, the investigators may 
submit a request to treat an additional 
15 patients. 
"Following surgical dobulking, 
patients will receive a maximum of 3 
intralesional injections of the GlTkSvNa 
vector-producing cell line (VPC) to 
induce regression of residual tumor 
cells by ganciclovir (GCVJ therapy- 
Recombinant DNA Research, Volume 17 
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