Federal Register / Vol. 59, No. 150 / Friday, August 5, 1994 / Notices 
40173 
App>endix M— I-D-1— c 
What is the length of time that potential 
participants will have to make a decision 
about their participation in the study? 
Appendix M-l-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 shojtld 
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 document 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 be provided with 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. 
Appendix M-I-D-2-a-(2). Alternatives 
“The Informed Consent document should 
indicate the availability of therapies and the 
possibility of other investigational 
interventions and approaches. 
Appendix M-I-D-2-a-{3). Voluntary 
Participation 
“The subjects should be informed that 
participation in the study is voluntary and 
that failiue 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. 
Appendix M-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 studies that are not reasonably expected 
to provide a therapeutic benefit to subjects, 
the Informed Consent document should 
clearly state that cro 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. 
Appendix M-l-D-2-a-(5). Possible Risks, 
Discomforts, and Side Effects 
“There should be clear itemization in the 
Informed Consent document of types of 
adverse experiences, their relative severity, 
and their expected frequencies. For 
consistency, the following definitions are 
suggested: side effects that are listed as mild 
should be ones which do not require a 
therapeutic intervention; moderate side 
effects require an intervention; and severe 
side effects are potentially fatal or life- 
threatening, disabling, or require prolonged 
hospitalization. 
“If verbal descriptors (e.g., ‘rare,’ 
‘uncommon,’ or ‘fii^uent’) are used to 
express quantitative information regarding 
risk, these terms should be explained. 
“The Informed Consent document should 
provide information regarding the 
approximate number of people who have 
previously received the genetic material 
under study. It is necessary to warn potential 
subjects that, for genetic materials previously 
used in relatively few or no humans, 
unforeseen risks are possible, including ones 
that could be severe. 
“The Informed Consent document should 
indicate any possible adverse medical 
consequences that may occur if the subjects 
withdraw from the study once the study has 
started. 
Appendix M-I-D-2-a-(6). Costs 
“The subjects should be provided with 
specific information about any financial costs 
associated with their participation in the 
protocol and in the long-term follow-up to 
the protocol that are not covered by the 
investigators or the institution involved. 
“Subjects should be provided an 
explanation about the extent to which they 
will be responsible for any costs for medical 
treatment required as a result of research- 
related injury. 
Appendix M-I-D-2-b. Specific Requirements 
of Gene Transfer Research 
Appendix M-I-D-2-b-(l). Reproductive 
Considerations 
“To avoid the possibility that any of the 
reagents employed in the gene transfer 
research could cause harm to a fetus/child, 
subjects should be given information 
concerning possible risks and the need for 
contraception by males and females during 
the active phase of the study. The period of 
time for the use of contraception should be 
specified. 
“The inclusion of pregnant or lactating 
women should be addressed. 
Appendix M-I-D-2-l>-(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 phase of the 
study. The Informed Consent document 
should include a list of persons who can be 
contacted in the event that questions arise 
during the follow-up period. The principal 
investigator should request that subjects 
continue to provide a current address and 
telephone number. 
“The subjects should be informed that any 
significant findings resulting from the study 
will be made known in a timely manner to 
them and/or their parent or guardian 
including new information about the 
experimental procedure, the harms and 
benefits experienced by other individuals 
involved in the study, and any long-term 
effects that have been observed. 
Appendix M-I-D-2-b-(3). Request for 
Autopsy 
“To obtain vital information about the 
safety and efficacy of gene transfer, subjects 
should be informed that at the time of death, 
no matter what the cause, permission for an 
autopsy will be requested of their families. 
Subjects should be asked to advise their 
families of the request and of its scientific 
and medical importance. 
Appendix M-I-D-2-b-(4). Interest of the 
Media and Others in the Research 
“To alert subjects that others may have an 
interest in the innovative character of the 
protocol and in the status of the treated 
subjects, the subjects should be Informed of 
the following: (i) that the institution and 
investigators will make efforts to provide 
protection from the media in an effort to 
protect the participants’ privacy, and (ii) that 
representatives of applicable Federal 
agencies (e.g., the National Institutes of 
Health and the Food and Drug 
Administration), representatives of 
collaborating institutions, vector suppliers, 
etc., will have access to the subjects’ medical 
records.’’ 
B. Amendment to Appendix M-VI of the 
NIH Guidelines Regarding Procedures to 
be Followed for Expedited Review of 
Single Patient Human Gene Transfer 
Experiments 
Appendix M-VI, Procediues to be 
Followed for Expedited Review of 
Single Patient Human Gene Transfer 
Experiments, will read as follows: 
“Appendix M-VI^. Regardless of the 
method of review, the Points to 
Consider is the standard of review for 
all gene transfer protocols; therefore, 
submission of the Points to Consider is 
required.’’ 
C. Deletion of Appendix L of the NIH 
Guidelines Regarding Release into the 
Environment 
Appendix L, Release into the 
Environment of Certain Plants, be 
deleted in full: To see the full text of 
Appendix L, reference the background 
information and decisions on actions 
under the NIH Guidelines (SecUon I-C). 
OMB’s “Mandatory Information 
Requirements for Federal Assistance 
Program Annoimcements” (45 FR 
39592) requires a statement concerning 
the official government programs 
contained in the Catalog of Federal 
Domestic Assistance. Normally NIH lists 
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