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Federal Register / Vol. 55. No. 41 / Thursday. March 1. 1990 / Notices 
Subcommittee met on March 31. 1989. 
and developed a draft revision of the 
. crigiiiaLdocumenL 
On July 31,. 1989. the Human Gene 
Therapy Subcommittee met to consider 
this document. The title and scope of the 
1986 document were revised to reflect 
the Subcommittee’s experiences 
reviewing a proposal for human gene 
transfer. 
The Points to Consider document was 
published for comment in the Federal 
Register of September 1. 1989 (54 FR 
36698). 
The RAC considered this document at 
the October 6. 1989. meeting. 
After a title revision, the RAC voted 
to approve the following version as the 
final document: 
NATIONAL INSTITUTES OF HEALTH 
Points to Consider in the Design and 
Submission of Protocols for the Transfer of 
Recombinant ONA into the Genome of 
Human Subjects 
Human Gene Therapy Subcommittee NIH 
Recombinant DNA Advisory Committee 
OUTLINE 
Applicability 
Introduction 
L Description of Proposal 
A Objectives and rationale of the 
proposed research 
1. Use of recombinant DNA for therapeutic 
purposes 
2. Transfer of recombinant DNA for other 
purposes 
B. Research design, anticipated risks and 
benefits 
1. Structure and characteristics of the 
biological system 
Z Preclinical studies, including risk 
assessment studies 
3. Clinical procedures, including patient 
monitoring 
4. Public health considerations 
5. Qualifications of investigators, adequacy 
of laboratory and clinical facilities 
C Selection of patients 
D. Informed consent 
E. Privacy and confidentiality 
II. Special Issues 
A Provision of information to the public 
B. Communication of research methods and 
results to investigators and clinicians 
m. Requested Documentation 
A Original protocol 
B. IRB and SC minutes and 
recommendations 
C. One-page abstract of gene transfer 
protocol ■ ■ - - 
D. One-page description of proposed 
■’■experiment in non-technical language 
' - vEL Curricula vitae for key professional 
persormcl 
F. Indication of other federal agencies to 
which the protocol is being submitted 
C. Other pertinent material 
IV. Reporting Requirements. 
National Institutes of Health 
Points to Consider in the Design and 
Submission of Protocols for the Transfer of 
Recombinant DNA into Human Subjects 
Applicability 
These Points to Consider apply to research 
conducted at or sponsored by an institution 
that receives any support for recombinant 
DNA research from the National Institutes of 
Health (NIH). Researchers not covered by the 
NIH Guidelines for Research Involving 
Recombinant DNA Molecules (51 FR 16959) 
are encouraged to use the Points to Consider. 
Experiments in which recombinant DNA is 
introduced into cells of a human subject with 
the intent of stably modifying the subject's 
genome are covered by Section ni-A— 1 of the 
NIH Guidelines for Research Involving 
Recombinant DNA Molecules. Section Ill-A- 
4 applies both to recombinant DNA and to 
DNA or RNA derived from recombinant 
DNA 
Introduction 
(1) This document is intended to provide 
guidance in preparing proposals for NIH 
consideration under Section ni-A-4 of the 
NIH Guidelines for Research Involving 
Recombinant DNA Molecules. Section lU-A- 
4 requires experiments involving the transfer 
of recombinant DNA into human subjects to 
be reviewed by the NIH Recombinant DNA • 
Advisory Committee (RAC) and approved by 
the NIH. RAC consideration of each proposal 
will be on a case-by-case basis and will 
follow publication of a precis of the proposal 
in the Federal Register, an opportunity for 
public comment, and a review of the proposal 
by the Human Gene Therapy Subcommittee 
(the Subcommittee] of the RAC RAC 
recommendations on each proposal will be 
forwarded to the NIH Director for a decision 
which will then be published in the Federal 
Register. 
(2) In general, it is expected that the 
transfer of recombinant DNA into human 
subjects will not present a risk to public 
health or to the environment as the 
recombinant DNA is expected to be confined 
to the^human subject Nevertheless. Section 
I-B-4^ of the Points to Consider document 
spedBcally asks the researchers to address 
this point 
(3) This document will be considered for 
revision as experience in evaluating 
proposals accumulates and as new sdentific 
developments occur. This review will be 
carried out periodically as needed. 
(4) A proposal will considered by the 
RAC only after the protocol has been 
approved by the local Institutional Biosafety 
Committee (IBC) and by the local 
Institutional Review Board (IRB) in 
accordance with Department of Health'and 
Human Services (DHHS) Regulations for the 
Protection of Human Subjects (45 Code of 
Federal Regulations, part 46). (If a proposal 
involves children, special attention should be 
paid to subpart D of these DHHS regulations.) 
The IRB and IBC may, at their discretion, 
condition their approval on further specific 
deliberation by the RAC and its 
Subcommittee. Consideration of proposals by 
• the RAC may proceed simultaneously with 
review by any other involved federal 
agencies ‘ provided that the RAC is notified 
of the simultaneous review. Meetings of the 
Committee and the Subcommittee will be 
open to the public except where trade secrets 
or proprietary information would be 
disclosed. The committee prefers that the first 
proposals submitted for RAC review contain 
no proprietary information or trade secrets, 
enabling all aspects of the review to be open 
to the public. The public review of these 
protocols will serve to inform the public not 
only on the technical aspects of the proposals 
but also on the meaning and significance of 
the research. 
(5) The clinical application of recombinant 
DNA techniques raises two general kinds of 
questions: (i) The questions usually discussed 
by IRBs in their review of any proposed 
research involving human subjects: and (u) 
broader issues. The first type of question is 
addressed principally in part I of this 
document Several broader issues are 
discussed later in this Introduction and in 
part II below. 
(6) Following the Introduction, this 
document is divided into four parts. Part I 
requests a description of the protocol with 
special attention to the short-term risks and 
benefits of the proposed research to the 
patient ’ and to other people, the selection of 
patients, informed consent, and privacy and 
confidentiality. In part IL investigators are 
requested to address special issues pertaining 
to the free flow of information about the 
clinical trials. These issues lie outside the 
usual purview of IRBs and reflect general 
public concerns about biomedical research. 
Part ni summarizes other requested 
documentation that will assist the RAC and 
its Subcommittee in their review of the 
proposals. Part IV apecifies reporting 
requirements. 
(7) The RAC and its Subcommittee will not 
at present entertain proposals for germ line 
alterations but will consider for approval 
protocols involving somatic cell gene therapy. 
The purpose of somatic cell gene therapy is to 
treat an individual patient. e.g.. by inserting a 
properly functioning gene into a patient's 
somatic cells. In germ line alterations, a 
specific attempt is made to introduce genetic 
changes into the germ (reproductive) cells of 
an individual, with the aim of changing the 
set of genes passed on to the individual's 
offspring. ’ . „ 
(B) The acxreptability of human somatic cell 
gene therapy has been addressed in several 
public documents as well as in numerous 
academic studies. The November 1982 report 
of the President’s Commission for the Study 
of Ethical Problems in Medicine and 
Biomedical and Behavioral Research. Splicing 
Life, resulted from a two-year process of 
public deliberations and hearings: upon 
release of that report, a House subcommittee 
held three days of public hearings with 
witnesses from a wide range of fields from 
' the biomedical and social sciences to 
theology, philosophy, and law. In December 
1984. the Office of Technology Assessment 
released a background paper. Human Gene 
Therapy, which concluded: 
Civic, religious, scientific, and medical 
groups have all accepted, in principle, the 
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Recombinant DNA Research, Volume 14 
