Federal Register / Vol. 59, No. 150 / Friday, August 5. 1994 / Notices 
40171 
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 comjxinent. 
Appendix M-l-D-2-a-i2). Alternatives. 
‘‘The Informed Consent document should 
indicate the availability of therapies and the 
possibility of other investigational 
interventions and approaches. 
Appendix M-l~D-2-a-l3). 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 otherv'ise entitled. 
Appendix M-I-D-2 -o-( 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 Content document should 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. 
Appendix M-I-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 arc 
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 'fiiaquent') are used to 
express quantitative information regarding 
risk, these terms should be explain^. 
“The Informed Consent document should 
provide Information regarding the 
approximate number of people who have 
previously received the genetic material 
under study. It b necessary to warn potential 
subjeeb 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-T-D-2-b. Specific 
Requirements of Gene Transfer Research 
Appendix M-I~D-2-h-( 1 ). 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 bo 
specified. 
“The inclusion of pregnant or lactating 
women should be addressed. 
Appendix M-I-D-2-b-(2). Long-term 
follow-up. “To permit evaluation of long- 
term safety end efficacy of gene transfer, the 
prospective subjects should be informed that 
they are expect^ 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, 
autopsies are to be performed, if feasible. 
Subjects should be informed that at the time 
of death, no matter what the cause, 
permission for any 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-i4). 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." 
I accept this recommendation, and 
Appendix M-l-D, Informed Consent, of the 
NIH Guidelines will be added accordingly. 
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 
On April 29, 1994, Dr. Nelson Wivel 
of the Office of Recombinant DNA 
Activities, National Institutes of Health, 
Bethesda, Maryland, requested that 
Appendix M-VI, Procedures to be 
Followed for Expedited Review of 
Single Patient Human Gene Transfer 
Experiments, be amended to clarify 
submission requirements. 
The Procedures to be Followed for 
Expedited Review of Single Patient 
Human Gene Transfer Experiments 
currently reads: 
"Appendix M-VI-D. Regardless of the 
method of review, the Points to 
Consider is the standard of review for 
all gene transfer protocols.” 
Tne proposed amendment reads: 
“Appendix M-VI-D. Regardless of the 
method of review, the Points to 
Consider is the standard of review for 
all gene transfer protocols: therefore, 
submission of the response to the Points 
to Consider is required.” 
The proposed amendment was 
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 
amendment to Appendix M-VI. 
Procedures to be Followed for 
Expedited Review of Single Patient 
Human Gene Transfer Experiments, by 
a vote of 13 in favor, 0 opposed, and no 
abstentions. 
I accept this recommendation, and 
Appendix M-VI, Procedures to be 
Followed for Expedited Review of 
Single Patient Human Gene Transfer 
Experiments, of the NIH Guidelines will 
be amended accordingly. 
C. Deletion of Appendix L of the NIH 
Guidelines Regarding Release into the 
Enxnronment 
On April 29, 1994, Dr. Nelson Wivel 
of the Office of Recombinant DNA 
Activities, National Institutes of Health. 
Bethesda, Maryland, requested that 
Appendix L. Release into the 
Environment of Certain Plants, be 
deleted from the NIH Guidelines based 
on the following: (1) Section I of the 
NIH Guidelines allows experiments to 
proceed that are reviewed and approved 
by another Federal agency that has 
jurisdiction for review and approval 
without the necessity for NIH review or 
approval (52 FR 31849); (2) the 
Recombinant DNA Advisory Committee 
has not reviewed any deliberate release 
experiment involving recombinant DNA 
since 1984; (3) at its May 30—31, 1991. 
meeting, the Recombinant DNA 
Advisory Committee recommended that 
Section III-A-2 be deleted from the NIH 
Guidelines; and (4) experiments 
involving deliberate release into the 
environment are currently reviewed 
within the framework of existing 
Federal regulations, as administered by 
the Environmental Protection Agency 
and the U.S. Department of Agriculture. 
Section I of the NIH Guidelines was 
amended on August 24, 1987, such that 
any recombinant DNA experiment 
(other than human gene transfer) may 
Recombinant DNA Research, Volume 19 
[ 751 ] 
