Attachment V - Pg. 1 
Points to Consider 
Introduction 
Experiments in which reccmbinant ENA is introduced into human cells with the 
intent of stably modifying the gencme of cells of a human subject are covered 
by Section III-A-4 of the NIH Reccmbinant ENA Guidelines, which require such 
experiments to be approved by the RAC and NTH. RAC consideration will follow 
review of the proposal by a working group of the RAC. RAC recommendation on 
proposals will be forwarded to the NIH Director for consideration . Final 
decisions will be published in the Federal Register, along with the text of 
approved proposals. 
This document is intended to provide guidance in preparing proposals for NIH 
consideration under Section III-A-4. Points mentioned in the document will not 
necessarily require attention in every proposal . It is expected that the 
document will be considered for revision at least annually as experience in 
evaluating proposals grows. 
Proposals considered by the RAC should have had prior evaluation by the relevant 
local IRB under requirements of the Office for the Protection of Human Subjects. 
Proposals which involve children should give specie! attention to Subpart D of 
the Protection of Human Subjects Regulations. Recommendation of the IRB and 
relevant minutes of its meetings should accompany submission of the proposal 
to NIH. The IRB may, at its discretion, make reccrrmendations that are conditional 
on further specific deliberation by the RAC on matters beyond the IRB charge 
or capability. 
Consideration of proposals by any other involved federal agency (e.g. , FDA) 
may proceed simultaneously with NIH consideration, with appropriate notification 
of the agencies involved. RAC consideration will address not only technical 
aspects of proposals but will extend to broader implications, such as individual 
and public health and ethical and social aspects. Clarification of such questions 
as the following in the proposal itself may facilitate the review process: 
What aspect in the proposal itself may facilitate is unprecedented? What prece- 
dents exist for any or all aspects of the proposal that may appear to be unpre- 
cedented? Yhat aspects of the proposal have been, or may become, subjects of 
public concern and controversy? What steps to alleviate such concern have been, 
or vn.ll be, undertaken? 
The specie! attention required by the NIH Reccmbinant ENA guidelines for clinical 
application of reccmbinant DNA to human gene therapy focuses on two general 
kinds of questions. Part I raises points about the short-term risks and benefits 
of the proposal to the patient, to other people, or to the broader environments? 
in Part II, investigators are requested to address broader ethical and social 
issues of the research and its longer-term implications go beyond the usual pur- 
view of an IRB. Beyond the points specifically outlined in this document, the 
RAC welcomes comments by investigators that will help it to evaluate the 
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