6708 
Federal Register / VoL 59, No. 29 / Friday, February 11, 1994 / Notices 
expedited review of a single patient gene 
transfer protocol must provide detailed 
information regarding the necessity of 
expedited review.” 
[No changes — Part Vl-B through VI-F.l 
(Amendl ”Part Vl-G. The NIH (ORDA) will 
report to the RAC following expedited review 
and will include all of the materials on 
which the decision was based. The RAC will 
formally review the protocol at its next 
scheduled meeting. Patient privacy will be 
maintained.” 
(No changes — Part VI-H through Vl-J.) 
(Renuinber “Part VII. Footnotes." 
(No changes) “The Food and Drug 
A dmini stration (FDA) has jurisdiction over 
drug products Intended for use in clinical 
trials of human gene transfer. For general 
Information on FDA's policies and regulatory 
requirements, (see the Federal Register, 
Volume 51, pages 23309-23313, 1986)." 
(No changes) ‘The term "patient" and its 
variants are used in the text as a shorthand 
designation for "patient-subject" 
Xn. Amendments to Part I-D of the 
Points To Consider, NTH Guidelines, 
Regarding Informed Consent 
Ehiring the December 2—3, 1993, 
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. Zallen, Chair of the 
Working Group on Informed Consent 
Issues. Dr. Ellis noted the RAC'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 
Cx)nsent documents when gene therapy 
is separate from a clinical protocol, 
commitment to long-term patient 
foUow-up, and Gnancial responsibility 
of the institution for all research-related 
costs. During his presentation. Dr. Ellis 
provided the RAC 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 RAC draft a 
letter outlining their speciGc 
recommendations to OPRR for 
distribution and consideration by the 
local IRBs. 
In a memorandum dated December 
23, 1993, Dr. Ellis further clariGed the 
avenues that should be pursued by the 
RAC with regard to the “quality and 
content of informed consent documents 
into constructive changes in the 
informed consent process," speciGcally 
in relaGon to human gene transfer. Dr. 
Ellis recommended that the Points to 
Consider should be amended to 
introduce consistency in the Informed 
Consent document language; therefore. 
Part I-D of the Points to Consider has 
been expanded. Proposed Part I-D-1 
addresses the informed consent process. 
Proposed Part I-D-2 addresses the 
informed consent document. Part I-E 
has been incorporated into I-D-1 . The 
proposed amendments read: 
■'Part I-D-1. Informed Consent Process 
"In accordance with the requirements of 
DHHS regulations for the protection of 
human subjects (45 CFR, part 46). 
investigators shall indicate how patients will 
be Informed about the proposed study and 
how their consent will be solicited. If the 
study involves pediatric or mentally 
handicapped patients, describe the 
procedures for seeking the permission of 
parents or guardians and. where applicable, 
the assent of each patient 
"Part I-D-l-«. Communication of the Study 
to Potential Participants 
"Part l-D-l-a-(l). What processes or 
procedures will be used to identify 
individuals who might be candidates for the 
proposed study? 
"Part l-D-l-a-<2). Which members of the 
research group and/or the institution will be 
involved in contacting potential participants 
and in describing the study to them? Where 
will discussions or other means of informing 
such individuals about the proposed study 
take place? What is the len^ of time that 
potential participants will have to make a 
decision about their participation in the 
proposed study? 
"Part l-D-l-a-(3). How will the following 
items be dealt with during the informed 
consent process: 
"Part I-D-l-a-(3}-(a). How will the major 
points covered in Parts I-A through I-C of 
the Points to Consider be disclosed to 
jKJtential participant$ in the proposed study 
and/or their parents or guardians in language 
that is understandable to them? 
"Part I-D-l-e-(3)-(b). How will the 
innovative character and the theoretically 
possible adverse effects of the experiment be 
discussed with the subjects and/or their 
parents or guardians? How will the potential 
adverse effects of the experiment be 
compared with the consequences of the 
disease? 
“Part I-D-l-fl-(3)-{c). How will 
participants and/or their parents or guardians 
be informed about the Innovative character of 
the experiment and that their participation in 
the proposed study may lead to interest by 
the media? 
"Part I-D-l-l-(3>-(d). How will the 
participants and/or their parents or guardians 
oe Informed about the possible irreversible 
consequences of procedures performed? 
"Part I-D-l-e-(3Ho)- How will the 
participants and/or their guardians be 
Informed about any expectation that they 
will cooperate in long-term follow-up? 
"Part l-D-l-a-(3>-KG. How will the 
participants and/or their guardians bo 
informed about the adverse medical 
consequences that may occur if the subjects 
withdraw from the study once the 
experiment has started? 
"Part I-D-l-«-(3)-(g). How will the 
participants and/or their parents or guardians 
be informed that permission to perform an 
autopsy will be requested in the event of a 
subject's death? (An autopsy shall be 
requested due to the need for an accurate 
determination of the precise cause of the 
subject's death and the pKDtential knowledge 
that may be gained from such information.) 
"Part I-D- 1 -a-(3)-(h). How will estimates 
of any financial costs associated with 
participation in the experiment and in the 
long-term follow-up to the experiment that 
are not covered by the investigators or the 
institutions involved be provided to potential 
participants and/or their parents or 
guardians? How will comparable financial 
information for other available alternatives, 
including other investigational therapies, be 
provided? 
"Part I-I>-l-l-(l)-<4). If there are more 
potential candidates than the study can 
accommodate, how will the decision be made 
about which to include? How will those who 
are excluded be informed? 
"Part I-D-l-b. Privacy and Confidentiality 
"Part I-D-l-b-(l). Provide a description of 
the' measures that will be taken to protect the 
privacy of patients and their families as well 
as to maintain the confidentiality of the 
research date. 
"Part l-D-l-b-(2). Provide a description of 
the provisions that wlU be made to maintain 
the confidentiality of research data, 
especially in cases where data could be lined 
to individual patients. 
"Part I-D-l-b-<3). Provide a description of 
the provision that will be made to honor the 
wishes of individual subjects and/or the 
arents or guardians of pediatric or mentally 
andicapped patients, as to whether, when, 
or how tne identity of patients may be 
publicly disclosed. 
“Part I-D-l-c Special Issues 
"Although the following issues are beyond 
the normal purview of the local IRBs, the 
RAC requests that investigators respond to 
the following questions: 
"Part I-D-l-c-(l). Do you or your funding 
sources intend to protect under patent or 
trade secret laws either the products or the 
procedures developed in the proposed study? 
if so. what steps will be taken to permit as 
full communication as possible among 
investigators and clinicians concerning 
research methods and results? 
“Part I-D-l-o-(2). What steps will be 
taken to ensure that accurate and appropriate 
Information is made available to the public 
with respect to such public concerns as may 
arise from the proposed study? 
"Part I-D-2. Informed Consent Document 
"Part I-D-2-a. When gene transfer Is a 
procedure separate from an IRB-approved 
clinical protocol, separate informea Consent 
documents shall be submitted for both the 
gene transfer and clinical protocols. 
"Part l-I>-2-b. Investigators submitting 
human gene transfer proposals for RAC . 
review must include the Informed Consent 
document as approved by the local IRB. This 
document shall include the following 
specific Information in addition to any 
requirements of the DHHS regulations for the 
protection of human subjects (45 CFR. part 
46): 
"Part I-D-l-b-(f )• Purpose of the Study 
"For experiments in which there Is no 
therapeutic intent, an explanation shall be 
[ 8 ] 
Recombinant DNA Research, Volume 19 
