9102 
Federal Register / Vol. 58, No. 31 / Thursday, February 18, 1993 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
i 
National Institutes of Health 
Recombinant DNA Research: Actions 
Under the Guidelines 
AGENCY: National Institutes of Health, 
PHS, DHHS. 
ACTION: Notice of Actions Under the 
NIH Guidelines for Research Involving 
Recombinant DNA Molecules. 
SUMMARY: This notice sets forth seven 
actions to be taken by the Director, 
National Institutes of Health (NIH), 
under the May 7, 1986, NIH Guidelines 
for Research Involving Recombinant 
DNA Molecules (51 FR 16958). 
FOR FURTHER INFORMATION CONTACT: 
i Additional information can be obtained 
i from Dr. Nelson A. Wivel, Director, 
Office of Recombinant DNA Activities 
! (ORDA), Office of Science Policy and 
Legislation, National Institutes of 
Health, Building 31, room 4B11, 
Bethesda, Maryland 20892, (301) 496- 
9838. 
SUPPLEMENTARY INFORMATION: Today 
seven actions are being promulgated 
under the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
These seven proposed actions were 
published for comment in the Federal 
Register of January 3, 1992 (57 FR 316), 
May 6, 1992 (57 FR 19512), and August 
19, 1992 (57 FR 37680), and reviewed 
and recommended for approval by the 
NIH Recombinant DNA Advisory 
Committee (RAC) at its meetings on 
February 10, 1992, June 1-2, 1992, and 
September 14-15, 1992 
I. Background Information and 
Decisions on Actions Under the NTH 
Guidelines 
A. Addition to the Points to Consider in 
the Design and Submission of Protocols 
for the Transfer of Recombinant DNA 
into the Genome of Human Subjects 
Regarding Submission Requirements for 
Human Gene Transfer/Gene Therapy 
Protocols (March 1, 1990, 55 FR 7443) 
Dr. Donald Krogstad, member of the 
RAC, suggested an outline for 
submission requirements for human 
gene transfer/gene therapy protocols 
during the RAC meeting of February 11, 
1992. This outline reads as follows: 
“Suggestions for Focusing Discussion 
at the RAC. 
“I. Investigator-Submitted Material 
“Format. Consider having both 
written and oral material presented in 
similar formats — e.g., following the 
Points to Consider — with a 150-250 
word Abstract at the beginning of 
written material. When a proposal has 
been presented previously, there should 
be e short section (SI 50 words) detailing 
the major revisions since the previous 
submission. 
“Length of Written Material and Time 
fur Oral Presentation. Only on rare 
occasion is there significant new 
information after 20 pages of written 
material or 20 minutes of oral 
presentation. To expedite both written 
and oral review, written material could 
be limited to approximately 20 pages 
per proposal (not counting references, 
tables and figures), and oral 
presentations to 25 minutes. 
“II. Reviewers’ Responses 
“Format. Reviewers’ comments 
should slate explicitly whether the 
Points to Consider have been addressed 
satisfactorily, and whether questions of 
Safety and Efficacy have been resolved. 
They should state also whether a 
proposal is: 
“(a) Acceptable as written, 
“(b) Acceptable with specific 
revisions, or 
"(c) Unacceptable in its present form. 
“Discussion of Written Reviews. 
Discussion among the various reviewers 
and with the Principal Investigator 
should help to clarify substantive 
questions about the protocols, which 
currently occupies a substantial amount 
of time at the RAC. 
“Length of Time for Oral Presentation 
of Reviews. After discussion with other 
reviewers and the Principal Investigator, 
it should be possible to present most 
reviews orally in <5 minutes.” 
This request was published for 
comment in the Federal Register of May 
6, 1992 (57 FR 19512). 
On June 2, 1992, the Committee 
reviewed and recommended approval of 
the following guidelines by a vote of 18 
in favor, 0 opposed, and no abstentions. 
"Guidelines for the Submission and 
Review of Human Gene Transfer/ 
Therapy Protocols for Review by the 
Recombinant DNA Advisory Committee 
“I. INVESTIGATOR-SUBMITTED 
MATERIAL: 
“Written proposals should begin with 
the lay and scientific abstracts, followed 
by the Points to Consider and the 
material provided in the body of an R01 
(sections A-D). When a proposal has 
been submitted previously, there should 
be a short section (<200 words) 
immediately following the abstracts that 
summarizes major revisions since the 
last review. Length limitations are 4-5 
pages for the Points to Consider, 2 pages 
each for CVs (Biosketch format) and 20 
pages for the body of the proposal 
(excluding tables, figures, appendices, 
and manuscripts). Data provided must 
include a description of the elements in 
the vector, the source of that 
information, and the method by which 
sequence data were compiled, plus 3 
diskettes with the vector sequence in 
ASCII format. Written material from 
Principal Investigators must be 
submitted £8 weeks before the meeting 
at which it will be reviewed; written 
comments from the primary reviewers 
£4 weeks before the RAC meeting; and 
written responses from the Principal 
Investigators £2 weeks before the 
meeting. 
“Oral Presentations at RAC Meetings 
provide only a brief overview of the 
proposal; they should concentrate on 
questions raised by the reviewers before 
and at the meeting. Oral presentations 
should be <20 minutes: £10 minutes for 
the overview and <10 minute: for 
responses to the reviewers’ questions. 
‘TI. Reviewers’ Responses: 
“Written Reviews should emphasize 
issues related to gene marking, gene 
transfer or gene therapy. They should 
state explicitly whether the Points to 
Consider have been addressed 
satisfactorily, and should examine the 
scientific rationale, scientific context 
(relative to other proposals reviewed by 
the RAC), whether the preliminary in 
vitro and in vivo data were obtained in 
appropriate models and are sufficient, 
and whether questions related to safety, 
efficacy, and social and ethical context 
have been resolved. Whenever possible, 
criticisms of Consent Forms should 
include suggested revisions for the RAC 
to consider — provided as written 
alternatives. Reviews should also state 
whether the proposal is: 
“(a) Acceptable as written, 
“(b) Acceptable with specific 
revisions or after satisfactory responses 
to specific questions raised on review, 
or 
“(c) Unacceptable in its present form. 
“Oral Discussion of Reviews at the 
RAC Meeting. It should be possible to 
present most reviews orally within £5 
minutes.” 
I accept this recommendation and the 
Points to Consider of the NIH Guidelines 
will be amended accordingly. 
B. Addition of Appendix D-XXXTV to 
the NIH Guidelines 
In a letter dated May 1, 1992, Dr. 
Michael T. Lotze, University of 
Pittsburgh, Pittsburgh, Pennsylvania, 
indicated his intention to submit a 
human gene therapy protocol to the 
Recombinant DNA Advisory Committee 
for formal review and approval. The 
title of this protocol is: Gene Therapy of 
Cancer: A Pilot Study ofIL-4 Gene 
Modified Antitumor Vaccines. This 
Recombinant DNA Research, Volume 17 
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