Number 98-03 Human Subject Protections


July 1, 1998

Subject: NIH Policy Guidance on the Inclusion of Children in Research

Dear Colleague:

This letter informs Institutional Officials and Institutional Review Board (IRB) Chairs of new policy guidance from the National Institutes of Health (NIH) regarding the inclusion of children in research.

On March 6, 1998, NIH promulgated "NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects." The new NIH policy guidance applies to all initial (Type 1) applications/proposals and NIH intramural projects submitted to NIH for receipt dates after October 1, 1998. The guidance is available at A copy of the notice is also available from OPRR by FAX, by calling 301-594-0464 and requesting document #4.

The NIH policy guidance applies only to research supported or conducted by NIH. Institutions retain the latitude to determine the extent to which they will apply this policy guidance to research funded by Department of Health and Human Services (DHHS) components other than NIH, by other federal departments or agencies, or by nonfederal sources. Please note, too, that the Agency for Health Care Policy and Research (AHCPR) encourages consideration of the inclusion of children in health services research projects (see

It is important to note that the NIH policy guidance on inclusion of children applies even to categories of research that would otherwise be exempt from the DHHS regulations for Protection of Human Subjects (45 CFR Part 46). The NIH policy guidance does not, however, require IRBs to review research which is exempt under 45 CFR Part 46. Each institution retains the latitude to define in its Assurance the extent to which it will require IRB review of activities that meet the criteria for exemption at 46.101(b).*

*Institutions are reminded that exemptions at 46.101 (b)(1) and (b)(3) through (b)(6) are applicable to research involving children. The exemption at 46.101(b)(2) regarding educational tests is also applicable. However, the exemption at 46.101

The NIH policy guidance was developed because medical treatments applied to children are often based upon testing done only in adults, and scientifically evaluated treatments are often less available to children due to barriers to their inclusion in research studies. The NIH policy guidance further illuminates the regulatory requirement at 46.111 (a)(3) that IRBs determine that the selection of subjects is equitable prior to approving proposed research.

While NIHs presumption for studies it sponsors will now be to include children in research (with certain exceptions), the additional DHHS protections for children involved as subjects in research, found at Subpart D of 45 CFR Part 46, remain unchanged. Thus, as a condition for approval of proposed research involving children, IRBs must continue to find that the research satisfies the specific criteria delineated at Section 46.404, 46.405, 46.406, or 46.407 of the DHHS regulations.

IRBs are encouraged to assess their respective needs for pediatric expertise among the IRB voting membership, and act in accord with the requirements at Section 46.107 (a) to possess the professional competence necessary to review specific research activities and to consider inclusion of one or more individuals who are knowledgeable about and experienced in working with children. Section 46.107 (f) reminds IRBs that they may invite nonvoting individuals to assist in the review of issues which require expertise beyond, or in addition to, that available among voting IRB members.

IRBs are empowered by 45 CFR Part 46 and the institutions Assurance with OPRR to 1) approve, 2) request modification of, or 3) disapprove research based on their review and assessment of the extent to which the criteria specified in the NIH policy guidance and the protections required under DHHS regulations will be met in the proposed research.

OPRR encourages you to direct questions and comments about the new NIH policy guidance to the NIH contact points listed in the March 6, 1998 announcement. And, please feel free to contact OPRR regarding implementation of the NIH policy guidance.


Gary B. Ellis, Ph.D.J. Thomas Puglisi, Ph.D.
Office for Protection from Research Risks Division of Human Subject Protections