The NIH Policy on Inclusion of Children is referenced and described in Section 5.7. Instructions for item 9 of the Research Plan (for F applicants, item 12 on PHS Fellowship Supplemental Form – Research Training Plan) are as follows:
Create a section entitled “Inclusion of Children” and place it immediately following the section on the Inclusion of Women and Minorities and the Targeted/Planned Enrollment Table(s).
For the purpose of implementing these guidelines, a child is defined as an individual under the age of 21 years (for additional information see http://grants.nih.gov/grants/funding/children/children.htm).
Provide either a description of the plans to include children, including the particular age ranges to be included, or, if children (or a subset) will be excluded from the proposed research, application, or proposal, present an acceptable justification for the exclusion (see below).
If children are included, the description of the plan should include a rationale for selecting a specific age range of children. The plan also must include a description of the expertise of the investigative team for working with children at the ages included, of the appropriateness of the available facilities to accommodate the children, and the inclusion of a sufficient number of children to contribute to a meaningful analysis relative to the purpose of the study.
Scientific Review Groups will assess each application as being acceptable or unacceptable with regard to the age-appropriate inclusion or exclusion of children in the proposed research project.
When children are involved in research, the Additional Protections for Children Involved as Subjects in Research (45 CFR part 46 Subpart D) apply and must be addressed under the Protections Against Risk subheading (4.1.2.b).
Justifications for Exclusion of Children
For the purposes of this policy, all individuals under 21 are considered children; however, exclusion of any specific age group, such as individuals under 18, should be justified in this section. It is expected that children will be included in all NIH-defined clinical research unless one or more of the following exclusionary circumstances apply:
1. The research topic to be studied is not relevant to children.
2. Laws or regulations bar the inclusion of children in the research.
3. The knowledge being sought in the research is already available for children or will be obtained from another ongoing study, and an additional study will be needlessly redundant. Documentation of other studies justifying the exclusions should be provided. NIH program staff can be contacted for guidance on this issue if the information is not readily available.
4. A separate, age-specific study in children is warranted and preferable. Examples include:
a. The condition is relatively rare in children, as compared to adults (in that extraordinary effort would be needed to include children, although in rare diseases or disorders where the applicant has made a particular effort to assemble an adult population, the same effort would be expected to assemble a similar child population with the rare condition); or
b. The number of children is limited because the majority are already accessed by a nationwide pediatric disease research network; or
c. Issues of study design preclude direct applicability of hypotheses and/or interventions to both adults and children (including different cognitive, developmental, or disease stages or different age-related metabolic processes). While this situation may represent a justification for excluding children in some instances, consideration should be given to taking these differences into account in the study design and expanding the hypotheses tested, or the interventions planned, to allow inclusion of children rather than excluding them.
5. Insufficient data are available in adults to judge potential risk in children (in which case one of the research objectives could be to obtain sufficient adult data to make this judgment). Although children usually should not be the initial group to be involved in research studies, in some instances, the nature and seriousness of the illness may warrant their participation earlier based on careful risk and benefit analysis.
6. Study designs are aimed at collecting additional data on pre-enrolled adult study subjects (e.g., longitudinal follow-up studies that did not include data on children).
7. Other special cases can be justified by the investigator and found acceptable to the review group and the Institute/Center Director.
Human Subjects Research Policy includes DHHS regulations for the protection of human subjects and the following NIH policies related to human subjects research.
5.1 Protection of Human Subjects
The Department of Health and Human Services (DHHS) regulations for the Protection of Human Research Subjects provide a systematic means, based on established, internationally recognized ethical principles, to safeguard the rights and welfare of individuals who participate as subjects in research activities supported or conducted by the DHHS. The regulations stipulate that the awardee organization, whether domestic or foreign, bears responsibility for safeguarding the rights and welfare of human subjects in DHHS-supported research activities. The regulations require that all organizations engaged in nonexempt human subjects research supported or conducted by the DHHS hold a Federalwide Assurance (FWA) with the Office for Human Research Protections (OHRP), and establish appropriate policies and procedures for the protection of human subjects. These regulations, 45 CFR part 46, Protection of Human Subjects, are available from OHRP, Department of Health and Human Services, The Tower Building, 1101 Wootton Parkway, Suite 200, Rockville, MD; telephone: 1-866-447-4777 (toll-free) or (240) 453-6900; e-mail: email@example.com. In general, OHRP considers organizations that receive direct support from DHHS for the conduct of nonexempt human subjects research to be engaged in human subjects research. (For more information on whether an institution is engaged in human subjects research, refer to: http://www.hhs.gov/ohrp/policy/engage08.html). When a research project is conducted by multiple organizations, each organization that is engaged in nonexempt human subjects research must hold an FWA and comply with the regulations at 45 CFR 46.
Nonexempt research involving human subjects may only be conducted under a DHHS award if the engaged organization(s) is operating in accord with an approved FWA and provides verification that an Institutional Review Board (IRB) that is registered under the specific FWA has reviewed and approved the proposed activity in accordance with the DHHS regulations. No award to an individual will be made unless that individual is affiliated with an assured organization that accepts responsibility for compliance with the DHHS regulations. Foreign applicant organizations must also comply with the provisions of the regulations unless a determination of equivalent protections is made in accord with 45 CFR 46.101(h).
Under DHHS regulations to protect human subjects, certain research areas are exempt. However, if an applicant makes inappropriate designations of the noninvolvement of human subjects or of exempt categories of research, this may result in delays in the review of an application or an application not being reviewed. The PHS will make a final determination as to whether the proposed activities are covered by the regulations or are in an exempt category, based on the information provided in the Research Plan. With the exception of research projects that meet the criteria for Exemption 4, studies that are exempt from the human subjects regulatory requirements must still address the inclusion of women, minorities, and children in the study design.
Regulations of the Food and Drug Administration (21 CFR 50, 21 CFR 56) generally apply to biomedical research involving an unapproved drug, device or biologic and may apply to certain studies of approved products. Additional information on FDA regulations is available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm. If work falls under FDA's regulatory requirements, the grantee must follow both DHHS and FDA human subject protection regulations.
The National Institutes of Health Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines) apply to all projects (NIH-funded and non NIH-funded) involving recombinant DNA molecules that are conducted at or sponsored by an institution that receives NIH support for recombinant DNA research. See Part III, 2.9. Research Involving Recombinant DNA, including Human Gene Transfer Research.
Federal requirements to protect human subjects apply to most research on human specimens (such as cells, blood, and urine), residual diagnostic specimens, and medical information. Research involving existing data, documents, records, pathological specimens, diagnostic specimens, or tissues that are individually identifiable is considered “research involving human subjects.” The NIH Office of Extramural Research Human Subjects Web site contains additional information and Frequently Asked Questions to help investigators understand how these federal requirements apply to their research. See: http://grants.nih.gov/grants/policy/hs/index.htm.
The DHHS regulations require the NIH to evaluate all applications and proposals involving human subjects (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.120). This independent evaluation is conducted at the NIH through the peer review system and NIH staff review, and, as required, will take into consideration the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. On the basis of this evaluation, the NIH may approve or disapprove the application or proposal, or enter into negotiations to develop an approvable one.