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Federal Register 1 Vol. 59, No. 127 t Tuesday, July 5, 1994 / Notices 
how their consent will be solicited. The 
consent procedure should adhere to the 
requirements oT DHHS regulations for 
the protection of human subjects (45 
Code of Federal Regulations, Part 46). If 
the study Involves pediatric or mentally 
handicapped patients, describe 
procedures for seeking the permission of 
parents or guardians and, where 
applicable, the assent of each patient. 
Areas of special concern include 
potential adverse effects, financial costs, 
privacy, long-term follow-up and post- 
mortem examination. When gene 
transfer is a procedure separate from a 
clinical protocol. Informed Consent 
documents shall be submitted for both 
the gene transfer and clinical protocols. 
Appendix M-I-D-1. How will the 
major points covered in Appendices M- 
1-A through M-I-C be disclosed to 
potential participants in this study and/ 
or parents or guardians in language that 
is understandable to them? 
Appendix M-I-D-2. How will the 
innovative character and the 
theoretically possible adverse effects of 
the experiment .be discussed with 
patients and/or .parents or guardians? 
How will the potential adverse effects 
be compared with the consequences of 
the disease? 
Appendix M-I-D-3. What 
explanation of the finaircial costs of the 
experiment, follow-up care, and any 
available ahematives will be provided 
to patients and/or parents or guardians? 
Appendix M-l-O-4. How will 
patients and/or their parents or 
guardians be informed that the 
innovative-character of the experiment 
may lead to great interest by the media 
in Ae research and in the treated 
patients? 
Appendix M-I-D-5. How will the 
patients and/or their parents or 
guardians be informed aboutt (i) the 
irreversible consequences of some of the 
procedures performed? (ii) any adverse 
medical consequences that may occur if 
the subjectfs) withdraws from the study 
once it has begrm? (iii) expectations of 
willingness to cooperate in long-term 
follow-up? and (iv) expectations that 
permission to perform an autopsy will 
be granted in the event of a patient’s 
death as a precondition for a patient’s 
participation in the study? This 
stipulation is included b^ause an 
accurate determination of the precise 
cause of a patient’s death would be of 
vital importance .to all future patients. 
Appendix M-4-E. Privacy and 
Confidentiality 
Indicate what measure will be taken 
to protect the privacy of patients and 
their families as well as to maintain the 
confidentiality of research data. 
Appendix M-I-E-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. 
Appendix M-I-E-2. What provision 
will be made to maintain the 
confidentiality of research data, at least 
in cases where data could be linked to 
individual patients? 
Appendix M-U. Special Issues 
Although the following issues are 
beyond the normal purview of local 
Institutional Review Boards, the RAC 
requests that Principal Investigators 
respond to Appendices M-Il-A and M- 
II-B below: 
Appendix M-Il-A. What steps will be 
taken, consistent with Appendix M-I-E, 
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? 
Appendix M-II-B. Do you or your 
funding sources intend to protect under 
patent or trade secret laws either the 
products or the procedures devel6ped in 
the proposed study? If so, what steps 
will be taken to permit as full 
communication as possible among 
Principal Investigators and clinicians 
concerning research methods and 
results? 
Appendix M-Ul. Guidelines for the 
Submission of Human Gene Transfer 
Protocols 
Appendices M-UI-A through M— III-D 
and M-IV apply to human gene transfer 
protocols considered under Bection III- 
A-2 and lII-B-2. Appendices M-IU-A, 
M- IV, and M-V apply to human gene 
transfer protocols considered under 
Section UI- B-2. 
Appendix M-UI-A. Principal 
Investigator-Submitted Material 
Principal Investigators should submit 
the following materials to the Office of 
Recombinant DNA Activities, National 
Institutes of Health, Building 31, Room 
4B11, Bethesda, Maryland 20892, (301) 
496-9838. 
Appendix M-UI-A— L. Written 
proposals shall be submitted in the 
following order: 
(1) Scientific abstract — 1 page; (2) 
non-technical abstract — 1 page; f 3) 
Institutional Biosafety Committee and 
Institutional Review Board approvals 
and their deliberations pertaining to 
your protocol; (4) Response to Points to 
Consider — 5 pages f see Appendix M 
through M-TU); (6) protocol — 20 pages 
excluding appendices — approved by the 
local Institutional Biosafety Committee 
and Institutional Review Board);. (7) 
Informed Consent document— -approved 
by the Institutional Review Board; Jfl) 
appendices including tables, figures, 
and manuscripts; (9) curricula vitae — 2 
pages for each key professional person 
in biographical sl^tch format; and (10) 
an indication of other Federal agencies 
to which the protocol is being submitted 
for review. 
Appendix M-III-A-2. When a 
proposal has been submitted previously, 
there should be a short section f< 200 
words) immediately following the 
abstracts that summarizes the major 
revisions since the last review. 
Appendix M-Ul—A-3. Data provided 
shall include; (i) A description of the 
elements in the vector, (ii) the source of 
that information, f iii) the method by 
which sequence data w'ere compiled, 
and (iv) three 3Vz inch diskettes with 
the vector sequence in ASCU format. 
Appendix M-TII— B. Time Frame for 
Submissions 
Note: Time frames are applicable only to 
protocob that are determined by NIH/ORDA 
to require full RAC review and NIH Director 
approval. Time frames do not apply to 
Accelerated Review human gene transfer 
experiments (see Sectkin IU-B-2 or those 
that only require lustration with NH4/ 
ORDA (see Section III-C- 7). 
Appendix M-III—B—1 . Written 
material from Principal Investigator 
shall be submitted < 8 weeks before the 
RAC meeting at which it will be 
reviewed. 
Appendix M-liI-B-2. Written 
comments from the primary reviewers 
to the Principal Investigator shall he 
submitted ^ 4 weeks before the RAC 
meeting at which it will be reviewed. 
Appendix M-iII-B-3. Written 
responses (frududing critical data in 
response to the primary reviewers' 
comments) shall be submitted by the 
Principal investigator to NIH/ORDA < 2 
weeks before the RAC meeting. 
Appendix M-ITI-C. Oral Responses to 
the RAC 
Principal Investigators shall limit 
their oral responses to the RAC only to 
those questions that are raised during 
the meeting. Oral presentations of 
previously submitted material and/or 
critical data that was not submitted < 2 
weeks piicar to the RAC meeting are 
prohibited. 
Appendix M-HI-D. Primary Reviewers' 
Responses 
Appendix M-III-D-l . Prima^ 
Reviewers’ 'Written Comments. The 
primaiy reviewers’ written comments 
on a proposal should include the ■ 
following: 
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