Federal Register / Vol. 59, No. 90 / Wednesday. May 11, 1994 / Notices 
24619 
pending full Recombinant DNA 
Advisory Committee review of 
additional information passed by a vote 
of 18 in favor, 0 opposed, and no 
abstentions. 
In a letter dated January 5, 1994, Dr. 
Freedman submitted a revised protocol 
to the Recombinant DNA Advisory 
Committee for formal review and 
approval. At its March 3—4, 1994, 
meeting, the Recombinant DNA 
Advisory Committee deferred the 
protocol until the investigator returns to 
the full Recombinant DNA Advisory 
Committee with: 
(1) A modified protocol, which 
includes a revised treatment schema 
that will provide statistically significant 
information, and 
(2) A revised Informed Consent 
document that adequately describes the 
procedures that will be performed in 
language.understandable to lay persons. 
The motion to defer the protocol 
pending full Recombinant DNA 
Advisory Committee review of the 
additional information passed by a vote 
of 12 in favor, 1 opposed, and no 
abstentions. 
In a letter dated April 13, 1994, Dr. 
Freedman submitted a revised protocol 
to the Recombinant DNA Advisory 
Committee for formal review and 
approval. 
VIII. Addition to Appendix D of the 
NIH Guidelines Regarding a Human 
Gene Transfer Protocol/Drs. Deisseroth, 
Hortobagyi, and Champlin 
In a letter dated April 12, 1994, Drs. 
Albert Deisseroth, Gabriel Hortobagyi, 
and Richard Champlin of the M.D. 
Anderson Cancer Center, Houston, 
Texas, submitted the human gene 
transfer protocol entitled: Use of Safety- 
Modified Retroviruses to Introduce 
Chemotherapy Resistance Sequences 
into Normal Hematopoietic Cells for 
Chemoprotection During the Therapy of 
Breast Cancer: A Pilot Trial to the 
Recombinant DNA Advisory Committee 
for formal review and approval. 
D(. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol/Dr. Roth 
In a letter dated April 12, 1994, Dr. 
Jack Roth of M.D. Anderson Cancer 
Center, Houston, Texas, submitted the 
human gene transfer protocol entitled: 
Clinical Protocol for Modification of 
Tumor Suppressor Gene Expression and 
Induction of Apoptosis in Non-Small 
Cell Lung Cancer (NSCLC) with an 
Adenovirus Vector Expressing Wildtype 
p53 and Cisplatin to the Recombinant 
DNA Advisory Committee for formal 
review and approval. 
X. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer ProtocohDr. Lotxe 
In a letter dated April 13, 1994, Dr. 
Michael Lotze of the University of 
Pittsburgh, Pittsburgh, Pennsylvania 
submitted the human gene transfer 
protocol entitled: IL-12 Gene Therapy 
Using Direct Injection of Tumor with 
Genetically Engineered Autologous 
Fibroblasts to the Recombinant DNA 
Advisory Committee for formal review 
and approval. 
XI. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol/Drs. Liu and Young 
In a letter dated October 7, 1993, Drs. 
Johnson M. Liu and Neal S. Young of 
the National Institutes of Health, 
Bethesda, Maryland, submitted the 
human gene transfer protocol entitled: 
Retroviral Mediated Gene Transfer of 
the Fanconi Anemia Complementation 
Group C Gene to Hematopoietic 
Progenitors of Group C Patients to the 
Recombinant DNA Advisory Committee 
for formal review and approval. At the 
December 2-3, 1993, meeting, the 
Recombinant DNA Advisory Committee 
deferred the protocol imtil the 
investigators return to the full 
Recombinant DNA Advisory Committee 
with the following: 
(1) Murine data demonstrating in vivo 
expression of the FACC gene and safety 
data accumulated over a period of ^ 4 
months demonstrating that the FACC- 
transduced cells do not produce any 
untoward effects, i.e., malignant 
transformation: 
(2) Data (cited in Dr. Cynthia Dunbar’s 
December 1993 data management 
report. Protocol #9206-025) regarding 
the possibility that "stem cell factor 
could favor the growth of leukemic 
versus normal progenitors during ex 
vivo culture periods;’’ and 
(3) Revisea eligibility criteria sections 
for both the protocol and Informed 
Consent document that describe the 
necessity for bone marrow examination 
following each infusion. 
The consensus of the Recombinant 
DNA Advisory Committee was that the 
investigators were not required to 
submit this additional data until 4 
weeks prior to the Recombinant DNA 
Advisory Committee meeting at which 
the information is reviewed. Submission 
of previously reviewed information is 
not required. The motion to defer the 
protocol pending full Recombinant DNA 
Advisory Committee review of 
additional information passed by a vote 
of 14 in favor, 0 opposed, and 3 
abstentions. 
On May 2, 1994, Drs. Liu and Young 
submitted additional materials relating 
to the human gene transfer protocol to 
the Recombinant DNA Advisory 
Committee for formal review and 
approval. 
Xn. Amendment to Part I-D of the 
Points to Consider in the Design and 
Submission of Protocols for the 
Transfer of Recombinant DNA Into the 
Genome of Human Subjects, NIH 
Guidelines, Regarding Informed 
Consent/Dr. 2^11en 
During the December 2-3, 1993, 
Recombinant DNA Advisory Committee 
meeting. Dr. Gary Ellis, Director of the 
Office for Protection from Research 
Risks (OPRR), NIH, Bethesda, Maryland, 
responded to the written coinments 
submitted by Dr. Zallen, Chair of the 
Working Group on Informed Consent 
Issues. Dr. Ellis noted the Recombinant 
DNA Advisory Committee’s concern 
regarding specific issues that should be 
addressed in human gene transfer 
protocol Informed Consent documents, 
i.e., request for autopsy, 
recommendations for male/female 
contraception, separate Informed 
Consent documents when gene therapy 
is separate from a cfinical protocol, 
commitment to long-term patient 
follow-up, and financial responsibility 
of the institution for all research-related 
costs. During his presentation. Dr. Ellis 
provided the Recombinant DNA 
Advisory Committee with background 
information regarding the roles of both 
OPRR and local Institutional Review 
Boards (IRB) in the review of research 
proposals involving human subjects. Dr. 
Ellis recommended that the 
Recombinant DNA Advisory Committee 
‘ draft a letter outlining its specific 
recommendations to OPRR for 
distribution and consideration by the 
local ERBs. 
In a memorandum dated December 
23, 1993, Dr. Ellis further clarified the 
avenues that should be pursued by the 
Recombinant DNA Advisory Committee 
with regard to the “quality and content 
of informed consent documents into 
constructive changes in the informed 
consent process,” specifically in 
relation to human gene transfer. Dr. Ellis 
recommended that the Points to 
Consider should be amended to 
introduce consistency in the Informed 
Consent document language. 
During the March 3—4, 1994, 
Recombinant DNA Advisory Committee 
meeting. Dr. Doris Zallen, Qiair of the 
Working Group on Informed Consent, 
provided a summary of the proposed 
amendments to Part I-D, Informed 
Consent of the Points to Consider. Two 
versions of revised Part I-D were 
presented: 
Recombinant DNA Research, Volume 19 
[301] 
