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Federal Register / Vol. 59, No. 150 / Friday, August 5, 1994 / Notices 
DEPARTMENT OF HEALTH AND 
•OMAN SERVICES 
^tJonal 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 three 
actions to be taken by the Director, 
National Institutes of Health (NIH), 
under the NIH Guidelines for Reseeirch 
Involving Recombinant DNA Molecules 
(Federal Register, July 5, 1994, Part IV). 
FOR FURTHER INFORMATION CONTACT: 
Additional information can be obtained 
from Dr. Nelson A. Wivel, Director, 
Office of Recombinant DNA Activities 
(ORDA), Office of Science Policy and 
Technology Transfer, National Institutes 
of Health, Building 31, Room 4B11, 
Bethesda, Maryland 20892, (301) 496- 
9838. 
SUPPLEMENTARY INFORMATION: Today 
three actions are being promulgated 
under the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
These three proposed actions were 
ublished for comment in the Federal 
register of May 11, 1994 (59 FR 24618), 
and reviewed and recommended for 
approval by the NIH Recombinant DNA 
Advisory Committee (RAC) at its 
meeting on June 9-.10, 1994. 
I. Background Information and 
Decisions on Actions Under the NIH 
Guidelines 
A. Amendment to Appendix M-I-D of 
the NIH Guidelines Regarding Informed 
Consent for Human Gene Transfer 
Protocols 
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 comments 
submitted by Dr. 21allen, 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 the gene 
herapy aspects of the protocols are 
independent of an ongoing clinical 
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 IRBs. 
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 translating its concern 
about 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 NIH Guidelines 
should be amended to introduce 
consistency in Informed Consent 
document language. 
During the March 3-4, 1994, 
Recombinant DNA Advisory Committee 
meeting. Dr. Doris 21allen, C^air of the 
Working Group on Informed Consent, 
provided a summary of the proposed 
amendments to Appendix M-I-^, 
Informed Consent. .Two versions of 
revised Appendix M-I-D were 
presented: (1) the version drafted by the 
working group, and (2) a modified 
version incorporating the modifications 
suggested by Mr. Alex Capron. The 
Recombinant DNA Advisory Committee 
recommended that the working group 
should develop a consolidated version 
of Appendix M-I-D which includes 
language from both proposed 
documents. The Recombinant DNA 
Advisory Conunittee suggested that 
questions should be prefaced with an 
explanation as to the necessity for the 
requested information. 
On April 27, 1994, Dr. Zallen 
submitted revised amendments to 
Appendix M-I- D, Informed Consent, in 
response to the specific comments 
posed by the Recombinant DNA 
Advisory Committee at its March 3-4, 
1994, meeting. The proposed 
amendments were reviewed by the 
Recombinant DNA Advisory Committee 
during the June 9-10, 1994, meeting. 
The Recombinant DNA Advisory 
Committee approved a motion to accept 
the proposed amendments with minor 
editorial changes to Appendix M-I-D, 
Informed Consent, by a vote of 13 in 
favor, 0 opposed, and no abstentions. 
The amended version of Appendix 
M-I-D, Informed Consent, reads: 
Appendix M-I-D. Informed Consent 
In accordance with the requirements of 
DHHS regulations for the Protection of 
Human Subjects (45 CFR Part 46). 
investigators should indicate how subjects 
will be informed about the proposed study 
and the manner in which their consent will 
be solicited. They should also indicate how 
the Informed Consent document makes clear 
the special requirements of gene transfer 
research. 
Appendix M-I-D-1. Communication About 
the Study to Potential Participants 
Appendix M-I-D-l-a. 
Which members of the research group and/ 
or institution will be respionsible for 
contacting potential participants and for 
describing the study to them? What 
procedures will be used to avoid possible 
conflicts of interest if the investigator is also 
providing medical care to potential subjects? 
Appendix M-I-D-l-b. 
How will the major points covered in 
Appendices M-I-A through M-I-C be 
disclosed to potential participants and/or 
their parents or guardians in language that is 
understandable to them? 
Appendix M-I-D-l-c. 
What is the length of time that potential 
participants will have to make a decision 
about their participation in the study? 
Appendix M-I-D-l-d. 
If the study involves pediatric or mentally 
handicapped subjects, how will the assent of 
each person be obtained? 
Appendix M-I-D-2. Informed Consent 
Document 
“Investigators submitting human gene 
transfer proposals for Recombinant DNA 
Advisory Committee review must include the 
Informed Consent document as approved by 
the local Institutional Review Boards. A 
separate Informed Consent document should 
be used for the gene transfer portion of a 
research project when gene transfer is used 
as an adjunct in the study of another 
technique, e.g., when a gene is used as a 
’marker’ or to enhance the power of 
immunotherapy for cancer. 
“Because of the relative novelty of the 
procedures that are used, the potentially 
irreversible consequences of the procedures 
performed, and the fact that many of the 
potential risks remain undefined, the 
Informed Consent process should include the 
following specific information in addition to 
any requirements of the DHHS regulations for 
the Protection of Human Subjects (45 CFR 
46). Indicate if each of the specified items 
appears in the Informed Consent document 
or, if not included in the Informed Consent 
document, how those items will be presented 
to potential subjects. Include an explanation 
if any of the following items are omitted from 
the consent process or the Informed Consent 
document. 
Appendix M-I-D-2-a. General Requirements 
of Human Subjects Research 
Appendix M-I-D-2-a-(l). Description/ 
purpose of the study. “The subjects should l-e 
provided with a detailed explanation in nuir 
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Recombinant DNA Research, Volume 19 
