The purpose of the policy is to ensure that the knowledge gained from NIH-funded research is applicable to all those affected by the conditions under study. The previous policy addressed concerns that children were not appropriately included in clinical research. The new policy aims to address similar concerns regarding other age groups, including older adults. This group is also disproportionally absent in clinical research, likewise resulting in insufficient data regarding treatments and interventions for this population.
Section 2038 of the 21st Century Cures Act, enacted December 13, 2016, establishes 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. Therefore, the new policy addresses these requirements and outlines the responsibility of investigators for considering the age of their participants. As with the previous policy, individuals of all ages should be considered in clinical research, unless scientific or ethical reasons exist to exclude them.
The policy is effective as of January 25, 2019. All competing grant applications submitted for due dates on/after this date must comply with the policy, in addition to contract proposals responding to solicitations issued on/after this date and intramural studies initiated after this date.
All human subjects research, including research that is “exempt” in accordance with Sections 101(b) and 401(b) of 45 CFR 46 - Federal Policy for the Protection of Human Subjects, is subject to the current inclusion policy regarding children in clinical research.
The Inclusion Across the Lifespan Policy has an effective date of January 25, 2019, and also applies to all human subjects research, whether “exempt” or “non-exempt.”
The requirements for applications/proposals are similar: age-related inclusion must be addressed, including a rationale for the age range of study participants and justification for age-based exclusion.
The Inclusion Across the Lifespan policy has an additional requirement for progress reports: de-identified individual-level participant data on participant age at enrollment must be included. Age at enrollment may be reported in units ranging from hours to years.
The previous policies regarding children were designed to increase the opportunity for children to participate in research studies when the disease/condition of study impacts them and is appropriate under existing Federal guidelines. The Inclusion Across the Lifespan policy expands these considerations to all age groups in order to encourage scientific research that is beneficial for all individuals affected by a disease/condition of study, regardless of their age.
Yes. Both the Inclusion of Children in Clinical Research and the Inclusion Across the Lifespan policy apply to all NIH-conducted or supported research activities (including collaborative activities), whether foreign or domestic. The research proposals should be in conformance with national and local laws and regulations and should consider the local culture and conditions of the collaborating host countries.
The Inclusion Across the Lifespan policy requires submission of de-identified individual-level participant data, including participant age at enrollment, in progress reports. Age at enrollment may be reported in units ranging from hours to years.
Determination of the age range of a study population is dictated by the scientific question being asked. The PI will need to consider whether the disease, disorder, or condition is appropriate for specific age groups. Examples of situations in which exclusion of specific groups may be justifiable are listed in the Inclusion Across the Lifespan policy.
The planned age range for the study should be based on the scientific question that the research is designed to address. If the investigator is unable to find an age-appropriate sample in the locale of the applicant institution, investigators are encouraged to seek collaborations with other institutions. Particularly when multi-center clinical trials are proposed, the inclusion requirements may be met by combining recruitment from the multiple sites; in these trials, each clinical site must still describe its planned recruitment, and will be evaluated on that basis.
The Inclusion section in the PHS Human Subjects and Clinical Trials Information Form (Section 2.4) will continue to have the heading “Inclusion of Women, Minorities, and Children” until the next forms update. The Inclusion Across the Lifespan information should be included in this section. See the instructions under Inclusion of Children in the application guide for additional information.
The appropriateness of the rationale for selecting or excluding individuals of specific ages is reviewed at several steps in the process before an award is made.
The NIH Scientific Review Group (SRG) evaluates the appropriateness of the population studied in terms of the aims of the research and ethical standards, the expertise of the investigative team managing research with individuals of the ages included, and the appropriateness of the facilities. The SRG considers these in the overall priority score.
Advisory Councils/Boards review policy compliance as part of the general secondary level of review of grant applications.
When an application is reviewed, a coding system is used to identify the age groups included in the proposed research and the rating of scientifically acceptable or unacceptable that reviewers provide for the age-related inclusion plans. For more information about the peer review process, visit the OER Peer Review website.
Previously, age-related inclusion codes were designed to specify the inclusion of children. The codes have been expanded to reflect the Inclusion Across the Lifespan policy. For age-related inclusion plans, the following codes may be indicated on the summary statement, with an “A” or “U” after the number to identify the plan as scientifically acceptable or unacceptable:
1 - Children, adults, and older adults
2 - Only children (no adults and older adults)
3 - No children included (only adults and older adults)
4 - Age representation unknown
6 - Children and adults (no older adults)
7 - Only adults (no children and older adults)
8 - Only older adults (no children and adults)
9 - Only children and older adults (no adults)
For example, a code of 1A indicates “Children, adults, and older adults, scientifically acceptable.”
Any application given an unacceptable code “U,” results in a bar-to-funding and must be resolved before the application/proposal is funded.
Regardless of the priority score, percentile ranking or program relevance of the proposed research, the NIH funding components will not fund/award grants, contracts, or intramural research projects that do not comply with this policy.
Program staff have the responsibility of ensuring that the study is in compliance with the policy, and review applications before award. Staff may also obtain additional information about "unacceptable" applications in the process of determining whether to fund application.
Updates to inclusion enrollment are provided in the Human Subjects System (HSS). Information on how to access HSS can be found here. To provide an update to an existing record, do not create a new inclusion enrollment report (IER). Instead, edit the existing inclusion enrollment report(s) as stated in these instructions. If you need to provide information about a new population that is not included in your current inclusion enrollment report(s), you may create a new IER by clicking the “Add New Inclusion Enrollment Report” button in the study record.
Yes, to make use of the system feature that uploads your cumulative enrollment information, the csv file template provided in the HSCT Post Submission form should be used. The template allows you to provide the individual-level data required by the Inclusion Across the Lifespan policy and aggregates the data to be displayed in the inclusion enrollment form for you upon upload.
To use the feature, do not modify the format of the template. The categories set in the columns should not be deleted or edited; the data for each participant can be entered on rows. For more information on how to use the template, check the instructions available in the HSS Online Help.