Federal Register / Vol. 55. No. 41 / Thursday, March 1. 1990 / Notices 
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b. About any adverse medical 
consequences that may occur if a subject 
'--withdraws from the study once it has begun? 
' . c. About expectations of willingness to 
' cooperate in long-term follow-up? • . " 
d. About expectations that permission to 
perform an autopsy will be granted in the 
event of a patient’s death following transfer 
'-.-as a precondition for a patient’s participation 
in the study? ’This stipulation is included 
because an accurate determination of the 
precise cause of a patient’s death would be of 
vital importance to all future patients. 
E. Privacy and confidentiality 
Indicate what measures will be taken to 
protect the privacy of patients and their - 
families as well as to maintain the 
confidentiality of research data. 
1. What provisions will be made to honor 
the wishes'of individual patients (and the 
parents or guardians of pediatric or mentally 
handicapped patients) as to whether, when, 
or how the identity of patients is publicly 
disclosed. 
2. What provision will be made to maintain 
the confidentiality of research data, at least 
in cases where data coiild be linked to' 
individual patients? 
n. Special Issues 
Although the following issues are beyond 
the normal purview of local IRBs, the RAC 
and its Subcommittee request that 
investigators respond to questions A and B 
below. 
A. What steps will be taken, consistent 
with point I-E above, 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? 
B. 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 . 
•I'llnvestigalors’ arid clinicians concerning ?-.»• ' 
research methods and results? 
IIL Requested Documentition 
In addition to responses to the questions 
raised in these Po’nls to Consider, please 
submit the following materials; 
A. Your protocol as approved by your local 
IRB and IBC. 
B. Results of local IRB and IBC 
deliberations and recommendations that 
^pertain to your protocol. 
C A one-page scientific abstract of the 
protocol. 
D. A one-page description of the proposed 
experiment in nontechnical language. 
E. Curricula vitae for key professional 
personnel. 
F. An indication of other federal agencies 
to which the protocol is being submitted for 
: review. • ■i . ■ 
■ C. Any other material which you believe 
will aid in the review. 
■i-IV. Reporting Requirements 
A- Serious adverse effects of treatment 
should be reported immediately to both the 
local IRB and the NIH Office for Protection 
from Research Risks, and a written report 
should be filed with both groups. A copy of 
the report should also be forwarded to the 
NIH Office of Recombinant DNA Activities 
(ORDA). 
■B. Reports regarding the general progress of 
patients should be filed with both your local 
IRB and ORDA within 6 months of the 
commencement of the experiment and at six- 
month intervals thereafter. These twice- 
i>-yearly reports should continue for a sufficient 
period of time to allow observation of all 
major effects. In the event of a patient’s 
■ death, a summary of the special post mortem 
studies and statement of the cause of death 
' should be submitted to the IRB and ORDA. if 
available. 
Footnotes; 
1. The Food and Drug Administration 
(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, 
please see the Federal Register, Volume 51, 
pages 23303-23313. 1986. 
2. The term “patient" and its variants are 
used in the text as a shorthand designation 
- ' for “patient-subject” 
1 accept this document as a source of 
information for investigators who will 
propose to do experiments involving the 
transfer of recombinant DNA into 
human subjects. 
F. Amendment to Appendix D-XIV of 
the NIH Guidelines. 
In a letter dated November 1. 1989. Dr. John 
R. Lowe. Chairman of the Institutional 
Biosafety Committee at the U.S. Army 
Medical Research Institute of Infectious 
Diseases (USAMRUD), requests that certain 
experiments involving products of a yellow 
fever virus originating from a 17-D yellow 
fever clone, but containing some sequences 
from the virulent Asibi strain of yellow fever 
virus, be carried out in animals at the BL-3 
’ containment level. 
Further, it is requested that there be a 
change in biocontainment for certain 
experiments involving vaccine studies of 
Venezuelan equine encephalitis virus: if this 
request should be approved, the animal 
■tudies in mice and hamsters then could be 
. done at the Biosafety Level (BL) 3 
containment level. It should be noted that the 
laboratory facilities proposed for these 
experiments operate at a BL-3 -f level of 
containment, which means that they possess 
some specific features characteristic of BL-4 
containment. 
These requests were published for 
comment in the Federal Register on 
January 4. 1990 (55 FR 392). and a 
correction notice published in the . 
Federal Register on January 22, 1990 (55 
FR 2152). 
■ • The RAC considered these requests at 
the February 5. 1990, meeting. 
On the first requesL the RAC, by a 
vote of 15 in favor, 0 opposed, and no 
abstentions, accepted the following 
motion: 
.To accept and pass the amendment to 
allow recombinant studies between the 
vaccine strain and the parental Asibi strain 
of yellow fever virus in Biosafety Level 3 
facilities using HEPA filters, and with 
vaccination of personnel as per the NIH-CDC 
Guidelines. 
On the second requesL the RAC. by a 
vote of 14 in favor, 0 opposed, and two 
abstentions, accepted the following 
motion: 
To accept the proposal to reclassify the 
work done with Venezuelan equine 
encephalitis virus clones and their attenuated 
mutants at Biosafety Level 3 using HEPA 
filters plus vaccination of personnel as per 
the NIH-CDC Guidelines. 
II. Summary of Actions 
A. Revision of Section III-A-2 of the 
NIH Guidelines. 
The amended version of section III- 
A-2 reads as follows: 
ni-A-2. Deliberate release into the 
environment of any organism containing 
recombinant DNA except those listed below. 
The term “deliberate release" is defined as a 
planned introduction of recombinant DNA- 
containing microorganisms, plants, or 
animals into the environment 
ni-A-2-a. Introduction conducted under 
conditions considered to be accepted 
scientific practices in which there is adequate 
evidence of biological and/or physical 
control of the recombinant DNA-containing 
organisms. The nature of such evidence is 
described in Appendices L M. N, and O. 
III-A-2-b. Deletion derivatives and single 
base changes not otherwise covered by the 
Guidelines. 
III-.A-2-C. For extrachromosomal elements 
end microorganisms (including vintses), 
rearrangements and amplifications within a 
single genome. Rearrangements involving the 
introduction of DNA ftnm different strains of 
the same species would not be covered by 
this exemption. 
B. Public Information Brochure — “Gene 
Therapy for Human Patients. " 
This brochure provides basic 
information for the nonscientific public 
about experiments intended to eyre 
disease through transplantation of genes 
into the nonreproductive (somatic) cells 
of human patients. It includes 
background material about human gene 
therapy, its purposes and potential, 
about supervision of the research, and 
about why and how the public is 
involved. 
This brochure is intended primarily as 
*educational material. This document is a 
report entirely separate from the NIH 
Guidelines. 
C. Amendment of Appendix H of the 
NIH Guidelines. 
The amended version of Appendix H 
reads as follows: 
Recombinant DNA Research, Volume 14 
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