This guidance document DOES NOT constitute policy, requirements, rules, regulations, or laws enforced by
NIH OBA or any other component of the Federal government. It is NOT a part of the NIH Guidelines for Research
Involving Recombinant DNA Molecules, nor does it amend Appendix M. Instead, it provides supplementary material
that may assist investigators and others in applying relevant sections of Appendix M, but its contents are
neither prescribed nor required.
All sample consent form language provided in the guidance has been made "generic" and is meant only to
illustrate how various issues could be conveyed; the samples are not endorsed by the above entities, are not
intended to stand in for complete sections of a gene transfer research consent form, and should not necessarily
be used verbatim. It is important to make informed consent language specific to each study design, population,
and purpose, as well as to the information and communication needs of potential participants. Investigators,
in consultation with their IRBs and IBCs, are best positioned to determine the most appropriate consent form
language for a given study.
Introduction to Guidance
"How will the major points covered in Appendix M-II, Description of Proposal,
be disclosed to potential participants and/or their parents or guardians in a language that is
understandable to them?"
Since before the first clinical gene transfer trial began enrolling subjects, the
National Institutes of Health (NIH)
and its Recombinant DNA Advisory Committee (RAC)
have sought to assist investigators in developing good consent forms
and processes for clinical gene transfer research.
Appendix M sections
M-IV were added to the
NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines)
to address points and issues related to informed consent
that would benefit from particular attention. These sections address issues unique to gene transfer, as well as issues that
gene transfer has in common with other forms of clinical research.
The requirements of Appendix M were always intended to be complementary to and are consistent with other requirements,
regulations, and guidance documents, including
45 CFR 46,
21 CFR 50, and
21 CFR 56, and other guidance from the
Office for Human Research Protections and the
Food and Drug Administration. However, even after the promulgation of
has continued to seek ways to assist investigators and others involved in the consent process for gene transfer trials.
In 2002, the NIH Office of Biotechnology Activities (NIH OBA)
formed a RAC Informed Consent Working Group - composed
of members of the RAC, outside experts, and representatives of the
Food and Drug Administration (FDA) and the
Office for Human Research Protections (OHRP)
- to assist the in the development of a comprehensive, web-based guidance document
to supplement Appendix M.
After an extensive development process, the guidance document was endorsed by the
The guidance provided here is intended to serve as a resource and learning tool for individuals involved in gene
transfer studies and others with an interest in this field.
Intended Audience: This guidance is intended to be useful to a variety of audiences:
- Investigators when providing information to potential participants about, and preparing informed consent forms for, gene transfer studies
- Sponsors of gene transfer research when drafting model consent forms and advising investigators on the consent form and process
- Institutional review boards (IRBs) and institutional biosafety committees (IBCs) when reviewing gene transfer protocols and consent forms
- Potential participants when making a decision about whether to participate in a gene transfer study
- The general public seeking to learn more about the issues involved in gene transfer research
How to Access the Guidance: The guidance can be viewed on this website or downloaded and printed in its entirety as
a pdf document. To view the guidance on the website, you may either start at the beginning and go
through the guidance page by page
by clicking on the navigational arrow, or click on the headers in the navigational menu on the left of the page to be directed to
the specific section that you want to read more about.
How to Maximize Utility of the Web-based Guidance: Each page of the guidance is devoted to a particular
section of Appendix M. In general, each page has five components:
- Excerpts from the NIH Guidelines - exact language from the relevant section of Appendix M
- Discussion - narrative expanding on the Appendix M section. Bolded subheadings identify specific areas of discussion relevant to the page's topic.
- Main Points - summary of the major ideas conveyed in the Discussion
- Sample Language - examples of how to implement the points made in the Discussion in the consent form as well as examples of what not to say
- Tools & Background Materials - links to various consent tools, web pages, and articles for more information about the page topic
This guidance was designed to be interactive when used on the Web. You can scroll over and click on any underlined words to access further information on that item, particularly in the Tools & Background Materials and Sample Language boxes.