The provisions of Subpart D, of the HHS regulations, Additional Protections for Children Involved as Subjects in Research apply to: All research involving children All research that is more than minimal risk All research funded by any federal agency All research funded by HHS

The provisions of Subpart D of the HHS (Department of Health and Human Services) regulations, which entail Additional Protections for Children Involved as Subjects in Research, specifically apply to "all research involving children." This means that if a research study includes individuals who are under the age of 18 (the definition of "children" in the context of the regulations), the additional protections outlined in Subpart D must be considered and adhered to, regardless of the level of risk posed by the research or the source of funding.

While Subpart D is primarily focused on research involving children and does not limit its provisions to research that is only of more than minimal risk, it does include different categories of research based on the level of risk and benefit involved. It stipulates various levels of review and approval that might be required for research with children, especially if the research presents more than minimal risk.

Federal regulations require that any research funded by HHS or any other federal agency must adhere to the Common Rule (which includes Subpart D when children are involved), but Subpart D specifically addresses the needs of children, regardless of the funding source. This means that even research not funded by HHS or any federal agency would still need to follow Subpart D if it includes children as research subjects.

Extra: The inclusion of children in research requires additional ethical considerations because children are considered a vulnerable population. They are less able to understand the nature and consequences of research, and therefore cannot give informed consent in the same way adults can. Subpart D outlines several key requirements that researchers must follow when children are research subjects:

1. **Parental permission**: Researchers must generally obtain permission from the parents or legally authorized representatives of the children.

2. **Assent from the child**: Depending upon the child's age, maturity, and psychological state, researchers must seek the assent of the child, which is a child's affirmative agreement to participate in research. Though it is not the same as consent, it’s an important step in respecting the autonomy of child participants.

3. **Categories of research**: Subpart D specifies three categories of research involving children—research not involving greater than minimal risk (45 CFR 46.404), research involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects (45 CFR 46.405), research involving greater than minimal risk with no prospect of direct benefit to individual subjects but likely to yield generalizable knowledge about the subject's disorder or condition (45 CFR 46.406), and research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children (45 CFR 46.407). Each of these has its own specific requirements regarding IRB (Institutional Review Board) review and approval.

4. **Risk assessment**: Depending on the risk level the research poses, the IRB must ensure that adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians.

The goal of Subpart D is to protect child subjects in research while allowing for important studies that can improve the health and wellbeing of children to proceed under careful oversight.