Notice Number: NOT-OD-18-116

Key Dates
Release Date: December 19, 2017

NOT-OD-16-010
NOT-98-024
NOT-OD-18-228
NOT-OD-18-227
NOT-OD-18-229

Issued by
National Institutes of Health (NIH)

Purpose

This revised Notice replaces NOT-98-024. The purpose of this Notice is to inform the research community that NIH is revising its NIH Policy and Guidelines on the Inclusion of Children. Changes to the policy include (1) the applicability of the policy to individuals of all ages, including children and older adults; (2) clarification of potentially acceptable reasons for excluding participants based on age; and (3) a requirement to provide data on participant age at enrollment in progress reports.

Background

NIH’s long-standing policy has been that children must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific or ethical reasons not to include them. This policy was developed due to concerns that children were not appropriately included in clinical research studies, resulting in insufficient data to establish the effectiveness of treatments in children.

Section 2038 of the 21st Century Cures Act, enacted December 13, 2016, enacts new provisions requiring NIH to address the consideration of age as an inclusion variable in research involving human subjects, to identify criteria for justification for any age-related exclusions in NIH research, and to provide data on the age of participants in clinical research studies. As required by the Act, on June 1-2, 2017 NIH held a workshop on Inclusion Across the Lifespan to discuss barriers and opportunities for participation of children and older adults in clinical research studies. This event is available on videocast at https://videocast.nih.gov/launch.asp?23334. In addition, NIH issued a Request for Information (RFI): Invitation to Comment on Inclusion in Clinical Research Across the Lifespan (NOT-OD-17-059) to solicit input from the wider scientific community and general public regarding appropriate inclusion of pediatric and older populations in research studies involving human subjects. NIH considered stakeholder input and reviewed current policies to identify opportunities to align NIH policies with the goal of ensuring that the distribution of study participants reflects the population needed to accomplish the scientific goals of the study.

Scope and Applicability

This policy applies to all NIH conducted or supported research involving human subjects, including research that is otherwise "exempt" in accordance with Sections 101(b) and 401(b) of 45 CFR 46 - Federal Policy for the Protection of Human Subjects.

The policy will apply to all competing grant applications for due dates on or after January 25, 2019. Ongoing, non-competing awards will not be expected to comply with this policy until the grantee submits a competing renewal application. For R&D contracts, the policy will apply to all solicitations issued on or after this effective date. For the intramural program, the policy applies to intramural studies submitted initiated on or after January 25, 2019.

Policy

It is the policy of NIH that individuals of all ages, including children (i.e. individuals under the age of 18) and older adults, must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific or ethical reasons not to include them. The inclusion of individuals across the lifespan as subjects in research must be in compliance with all applicable subparts of 45 CFR 46 as well as with other pertinent federal laws and regulations.

Applications or proposals for research involving human subjects must address the age-appropriate inclusion or exclusion of individuals in the proposed research project. Applications/proposals must include a description of plans for including individuals across the lifespan, including a rationale for selecting the specific age range justified in the context of the scientific question proposed. If individuals will be excluded from the research based on age, the recipient/offeror must provide an acceptable justification for the exclusion. Acceptable reasons for excluding individuals based on age may include:

• The disease or condition does not occur in the excluded age group, or the research topic is not relevant to the excluded age group.
• Example: A study of Alzheimer's disease proposes to exclude children.
• The knowledge being sought in the research is already available for the excluded age group or will be obtained from another ongoing study, and an additional study will be redundant.
• Example: A drug studied and approved for use in children will now be studied only in adults.
• A separate, age-specific study in the excluded age group is warranted and preferable. While this situation may represent a justification for excluding individuals based on age, consideration should be given to taking age differences into account in the study design, whenever feasible.
• Example: A clinical trial designed to promote self-monitoring of blood glucose levels in adolescents with Type 1 diabetes proposes to include only adolescents.
• The study will collect or analyze data on pre-enrolled study participants (e.g., longitudinal follow-up studies that did not include data on children, or analysis of an existing dataset) and data inclusive of individuals across the lifespan are not available to address the scientific question.
• Example: A study which began prior to implementation of the NIH Policy and Guidelines on the Inclusion of Children proposes follow-up to examine long-term outcomes of individuals with the condition. The original study excluded children, and similar data are not available from a cohort that includes children.
• There are laws or regulations barring the inclusion of individuals in a specific age group in research.
• Example: Regulations for protection of human subjects allow consenting adults to accept a higher level of risk than are permitted for children.
• The study poses an unacceptable risk to the excluded group, such that their participation would not be considered ethical by the local IRB, peer review and/or NIH staff.
• Example: Children are excluded from a Phase I study for a treatment that includes significant risk, including death. Evidence suggests the potential benefits to children do not outweigh the risks.

Scientific review groups at the NIH will assess each application/proposal as being "acceptable" or "unacceptable" with regard to the age-appropriate inclusion or exclusion of individuals in the research project, in addition to evaluating the plans for conducting the research in accord with these provisions. NIH staff will monitor implementation of this policy during the development, review, award and conduct of research; and manage the NIH research portfolio to comply with the policy.

Age Data Collection

NIH recipients/offerors must submit data on participant age at enrollment in progress reports. Investigators planning to conduct research involving human subjects should design their studies in such a way that de-identified individual-level participant data on sex/gender, race, ethnicity, and age at enrollment may be provided to NIH in progress reports. Age at enrollment may be reported to NIH in units ranging from hours to years. Recipients/offerors are responsible for ensuring informed consent documents allow submission of de-identified individual-level data on participant sex/gender, race, ethnicity, and age at enrollment to NIH.

Resources

Further information regarding NIH expectations for the inclusion of individuals across the lifespan is available at the following website: https://grants.nih.gov/grants/funding/children/children.htm.

Inquiries

Please direct all inquiries to:

NIH Inclusion Policy Officer
Office of Extramural Research (OER)
Telephone: 301-435-0921
Email: inclusion@od.nih.gov