Attachment III - Pg. 1 
Points to Consider 
Introduction 
Experiments in which recombinant DNA is introduced into human 
cells with the intent of stably modifying the genome of cells of a 
human subject are covered by Section III— A— 4 of the NIH Recombinant DNA 
Guidelines, which require such experiments to be approved by the RAC 
and NIH'. 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 special 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 recommendations 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 impacts. Clarification of such questions as the following 
in the proposal itself may facilitate the review process: What aspect 
of the proposal is unprecedented? What precedents exist for any or all 
aspects of the proposal that may appear to be unprecedented? What 
aspects of the proposal have been, or may become, subjects of public 
concern and controversy? What steps to alleviate such concern have 
been, or will be, undertaken? 
The special attention required by the NIH Recombinant DNA 
guidelines for clinical application of recombinant DNA to human gene 
therapy focuses on two general kinds of questions: 
1. Short-term risk and benefit 
Does the proposal pose a risk to the patient, to those 
who care for the patient, to other people, or 
to the broader environment? 
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