Federal Register / Vol. 57. No. 2 / Friday, January 3. 1392 / Notices 
319 
protocol? What are these? Have they 
'| resulted in a change in your procedures? 
“Section IV-D-3. Measure of Gene 
Transfer Success In Vivo. 
"Section IV-D-3 -a. Positive effects. 
'Section IV-D-3-a-(l). In the patients 
treated, has there been any evidence of 
activity of the transferred gene? what is 
j the documentation for this? How does 
this compare with what you anticipated? 
“Section IV-D-3-a-(2). Has the 
patients’ condition improved? 
“Section IV-D-3-a-{3). Is there 
significant variation between patients. If 
so. how is this explained? 
“Section IV-D-3-b. Negative effects. 
“Section IV-D-3-b-{l). Is there any 
evidence of adventitial spread of 
I transduced material? Was any tumor/ 
normal tissue obtained after transduced 
material was administered? Was a post 
mortem obtained? Was there any sign of 
gonadal transfer of genetic material? By 
what criteria? 
I “Section IV-D-3-b-{2). Is there any 
evidence of generation of replication 
I competent virus related to gene transfer 
procedure in patients? 
“Section IV-D-3-b-(3). What toxicity 
was seen? Local, at injection site, 
systemic, any evidence of allergy/ 
hypersensitivity/autoimmunity to the 
administered products? 
"Section IV-D-3-b-(4). Is there 
evidence of deterioration of the disease 
state in relation to therapy? 
“Section IV-D-3-b-(5). Is there any 
evidence of effects on other genes? 
“Section IV-D-3-b-{6). Are there 
problems that have occurred that you 
did not anticipate prior to starting the 
protocol? What are these? Have they 
resulted in a change in your procedures? 
“Section IV-D-4. Patient Accrual 
Data. 
“Section IV-D-4-a. How many 
i patients were considered for entry on 
[ study? 
“Section IV-D-4-b. For those who 
were rejected, what were the reasons? 
“Section IV-D-4-b-(l). Unavailability 
of tissue for transduction? 
"Section !V-D-$r-b-(2). Lack of ability 
to transduce tissue? 
“Section IV-D-4-b-{3). W 7 as that 
transduced tissue unable to be used? If 
not, give reason. 
"Section IV-EM-b-{4). Patient/ 
physician refusal to participate? 
“Section IV-D-4-b-{5). Other reasons 
not accepted in protocol? 
“Section IV-D-4-c. How many 
patients were actually entered? 
“Section IV-D-4-c-{l). Upon review, 
were all these patients eligible? If not. 
give reasons why not. 
“Section IV-DMb-d. Provide a coded 
list of patients on study along with their 
on-study dates, off-study dates, and 
reason for being taken off study. 
“Section IV-D-4-e. Are your patient 
accrual goals being met in a timely 
fashion? If not, why not. 
"Section IV-D-5. Have any 
publications {abstracts or articles) 
resulted from this work? If so, provide 
reprints. 
VIII. Amend Introduction, Section IV-B 
and V of the Points to Consider 
Regarding Review by the Human Gene 
Therapy Subcommittee; Amend Sections 
III-A and IV-C of the NIH Guidelines 
Regarding Publishing Notice of Meetings 
and Proposed Actions in the Federal 
Register 
A.t the Human Gene Therapy 
Subcommittee meeting on July 30-31. 
1991. the subcommittee requested that 
the Working Group on the Future Role of 
the Recombinant DNA Advisory 
Committee prepare a report about the 
feasibility of merging the Human Gene 
Therapy Subcommittee and the 
Recombinant DNA Advisory Committee. 
This request was published for 
comment in the Federal Register on 
November 4. 1991 {56 FR 56415). 
The Human Gene Therapy 
Subcommittee received a report from 
this working group during its meeting on 
November 21-22, 1991 which 
recommended that; (i) All eligible 
Human Gene Therapy Subcommittee 
members be added to the Recombinant 
DNA Advisory Committee as full voting 
members; or (ii) all of the Human Gene 
Therapy Subcommittee members be 
added to the Recombinant DNA 
Advisory Committee as non-voting 
members; or (iii) joint meetings would 
be held in which the subcommittee 
w’ould vote on the proposed action first 
followed by the full Recombinant DNA 
Advisory Committee. 
During the meeting, the following 
motion passed by a vote of 11 in favor. 2 
opposed, and no abstentions: 
“We move to recommend to the 
Recombinant DNA Advisory Committee, 
that its subcommittee, the Human Gene 
Therapy Subcommittee, be merged into 
the parent committee. The number of 
meetings per year of the Recombinant 
DNA Advisory Committee would 
increase to four per year. There would 
be a transition period of one year in 
which the Recombinant DNA Advisory 
Committee would begin to review 
proposed actions as the sole review 
group with the following provisions: (i) 
The Human Gene Therapy 
Subcommittee would codify a set of 
guidelines for shortening the review 
process, and (ii) the eligible members of 
the Human Gene Therapy Subcommittee 
would be brought onto the Recombinant 
DNA Advisory Committee as full voting 
members in keeping with the nomination 
process for Federal Advisory 
Committees." 
The Human Gene Therapy 
Subcommittee forwarded the proposal 
to the Recombinant DNA Advisory 
Committee for consideration during the 
February 10-11. 1992. meeting. 
In a letter dated December 23. 1991. 
Dr. Nelson Wivel, Director, Office of 
Recombinant DNA Activities. National 
Institutes of Health, Bethesda, 
Maryland, is making a request to enable 
the above transition to proceed more 
efficiently. His letter states: 
“* * * the Office of Recombinant 
DNA Activities (ORDA) is requesting 
that the following amendments be made 
to: (i) Sections III-A, IV-C-l-b-(l), IV- 
C-2, IV-C-3-b-{l), and IV-C-3-b-{2) to 
have the 30 day notice for Notice of 
Meeting and Proposed Actions be 
changed to a 15 day notice; and (ii) the 
Points to Consider in the Design and 
Submission of Protocols for the Transfer 
of Recombinant DNA into the Genome 
of Human Subjects in the sections of 
Introduction, IV-B, V. and the NIH 
Guidelines. Appendix D-XV, to have the 
Human Gene Therapy Subcommittee 
reviewing the human gene protocols 
changed to the Recombinant DNA 
Advisory Committee. 
“ORDA is proposing that if the RAC 
votes to approve the recommendation to 
merge the HGTS with the parent 
committee and to increase the number 
of meetings per year, that the following 
changes must be made to amend the 
National Institutes of Health (NIH) 
Guidelines for Research Involving 
Recombinant DNA Molecules: 
“I. Notice of Meeting and Proposed 
Actions. 
"The NIH Guidelines states that a 30 
day Notice of Meeting and Notice of 
Proposed Action be published in the 
Federal Register for public comment. 
Under the Federal Advisory Committee 
Act, only a 15 day notice is required. 
The recommendation being forwarded 
by the HGTS tc the RAC for approval 
would require an increase in the number 
of meetings per year. To more efficiently 
process the required paperwork prior to 
each meeting, the 30 day notice needs to 
be changed to a 15 day notice. It is 
proposed that the following changes be 
made: 
’Section III-A. Experiments that 
Require RAC Review and NIH and IBC 
Approval Before Initiations. 
’Experiments in this category cannot 
be initiated without submission of 
relevant information on the proposed 
experiment to NIH, the publication of 
the Proposal in the Federal Register for 
Recombinant DNA Research, Volume 15 
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