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Federal Register / Vol. 59, No. 90 / Wednesday, May 11, 1994 / Notices 
(1) The version drafted by the w’orking 
group, and 
(2) A modified version incorporating 
the modifications suggested by Mr. Alex 
Capron. The Recombinant DNA 
Advisory Committee recommended that 
the worldng group should develop a 
consoUdat^ version of part I-D which 
includes language from both proposed 
documents. The Recombinant DNA 
Advisory Committee 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 part 
I-D, Informed Consent, of the Points to 
Consider in response to the specific 
comments posed by the Recombinant 
DNA Advisory Committee at its March 
3—4, 1994, meeting. The proposed 
amendments read; 
Part I-D Informed Consent 
“In accordance with the requirements 
of DHHS regulations for the protection 
of human subjects (45 CFR part 46), 
investigators shall indicate how subjects 
will be informed about the proposed 
study, the manner in which their 
consent will be solicited, and that the 
informed consent form makes clear (he 
special requirements of gene transfer 
research. 
Part 1-D-l. Communication of the 
Study to Potential Participants 
Part I-D-l-a. Which members of the 
research group and/or institution will be 
responsible for contacting potential 
participants and for describing the study 
to them? What procedures will be used 
to avoid potential conflicts of interest if 
the investigator is also providing 
medical care to potential subjects? 
Part I-D-l-b. Where will discussions 
or other means of informing individuals 
about the proposed study t^e place? 
Part I-D-l-c. How will the major 
p>oints covered in Parts I-A through I- 
C of the Points to Consider be disclosed 
to potential participants and/or their 
parents or guardians in language that is 
understandable to them? 
Part l-D-l-d. What is the length of 
time that the potential participants will 
have to make a decision about their 
participation in the study? 
Part l-D-l-e. If the study involves 
pediatric or mentally handicapped 
subjects, how will the assent of each 
person be obtained? 
Part I-D-2. Informed (Consent Document 
"Investigators submitting human gene 
transfer proposals for Recombinant DNA 
Advisory Cx>nunittee review must 
include the Informed Consent document 
as approved by the local Institutional 
Review Board. A separate 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, such 
as when the gene is used as a ‘marker’ 
or when it is used 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 
possibility that many of the potential 
risks remain undefined, the Informed 
Consent 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). 
Indicate if each of the specified items 
appears in the consent form or, if not in 
the consent form, how those items will 
be presented to potential subjects. 
Include an explanation if any of the 
following items is omitted from the 
consent process or document. 
Part I-D-2-a. General Requirements of 
Human Subjects Research 
Part I-D-2-a-{l). Description/purpose 
of study. “The subjects should be 
provided a detailed explanation in non- 
technical language of the purpose of the 
study and the procedures associated 
with the conduct of the proposed study, 
including a description of the gene- 
transfer component. 
Part I-D-2-a-(2). Alternatives. “The 
consent form should indicate the 
availability of other therapies, including 
the possibility of other investigational 
therapies and approaches. 
Part I-D-2-a^3). Voluntary 
participation. “The subjects should be 
informed that participation in the study 
is voluntary and that failure to 
participate in the study, or withdrawal 
of consent, will not result in any penalty 
or loss of benefits to which the subjects 
are otherwise entitled. 
Part I-D-2-a-(4). Benefits. “The 
subjects should be provided with an 
accurate description of the possible 
benefits, if any, of participating in the 
proposed study. For experiments which 
are not reasonably expected to provide 
a therapeutic benefit to subjects, the 
consent form shall clearly state that no 
direct clinical benefit to subjects is 
expected to occur as a result of 
participation in the study, although 
knowledge may be gained that may 
benefit others. 
Part I-D-2-a-(5). Possible risks, 
discomforts, and side effects. “There 
should be a clear itemization in the 
consent form of types of adverse 
experiences, the relative severities, and 
the expected frequencies. For 
consistency of definition, side effects 
that are listed as mild should be ones 
which do not require a therapeutic 
intervention. M<>derate side effects 
require an intervention. Severe side 
effects are potentially fatal or life- 
threatening, disabling, or require 
prolonged hospitalization. Rare side 
effects occur in less than one in one 
thousand subjects, uncommon side 
effects in less than 1% of subjects, 
common side effects in one to 10% of 
subjects, and frequent side effects are 
those which occur in more than 10% of 
subjects. 
“The consent form should provide 
information regarding the approximate 
number of people who have received 
the genetic material under study. It is 
also necessary to warn potential subjects 
that for genetic materials previously 
used in relatively few or no humans, 
imforeseen risks are possible, including 
ones that could be severe. 
“Any possible adverse medical 
consequences that may occur if the 
subjects withdraw from the study once 
the experiment has started should be 
indicated. 
“Part I-D-2-a-(6). Costs. “The 
subjects should be provided with 
information about any financial costs 
associated with their 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. Comparable 
financial information for other available 
alternatives, including other 
investigational therapies, should also be 
provided. 
"In the consent form, subjects should 
be informed about the extent to which 
they will be responsible for any costs for 
medical treatment required as a direct 
result of research-related injury. 
Part I-E>-2-b. Specific Requirements of 
Gene Transfer Research ■ 
Part I-D-2-b-(l ). Use of barrier 
contraception. “To avoid the possibility 
that any of the reagents employed in 
gene transfer research could cause harm 
to a developing fetus, female subjects 
should be informed that they should not 
be pregnant during the course of their 
participation in the study. Both male 
and female subjects should be informed 
when barrier contraception is required 
during the active phase of their 
participation in the study. 
Part I-D-2-b-(2). Long-term follow 
up. “To permit evaluation of long-term 
safety and efficacy of gene transfer, the 
prospective subjects should be informed 
that they are expected to cooperate in 
long-term follow-up that extends 
beyond the active pha.se of the study. A 
list should be provided in the consent 
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Recombinant DNA Research, Volume 19 
