16. Subpart D Children: 404 to 407, Assent, Permission, and Wards
After this lesson you can
- Define children, assent, permission, and guardian under 45 CFR 46.402 and 21 CFR 50.3
- Apply the four risk categories in 46.404 through 46.407 and their FDA counterparts in 50.51 through 50.54
- State the assent and permission rules in 46.408 and 50.55, including when each may be waived
- Apply the wards provision in 46.409 and 50.56
- Describe protections for adults with impaired decision-making capacity, students, employees, and economically or educationally disadvantaged persons
Video coming soon
Scheduled for release on October 2, 2026.
Children in Research Under Subpart D: Categories 404 to 407 explains how four risk categories decide who signs and how many parents must give permission. This lesson covers 45 CFR 46 Subpart D and 21 CFR 50 Subpart D in full, plus assent, waivers of permission, and wards of the state.
5 Key Facts from This Lesson
- Category 404 covers research with no greater than minimal risk, and 405 covers greater than minimal risk with the prospect of direct benefit; both need permission from one parent.
- Categories 406 and 407 require permission from both parents unless one is deceased, unknown, incompetent, or not reasonably available, or only one has legal responsibility for the child.
- Category 406 requires a minor increase over minimal risk, experiences commensurate with the child's situation, and knowledge of vital importance about the child's own disorder or condition, so healthy children cannot be enrolled under it.
- Parental permission may be waived under 46.408(c) for populations such as abused or neglected children, a narrower route than the general waiver of consent.
- Wards of the state need an appointed advocate for 406 and 407 research, but not for 404 and 405 research.
Exam traps
The distinctions exam questions on this topic are most often built to test. Know them cold.
404 and 405 need one parent; 406 and 407 need both, with four exceptions
406 requires all three findings: a minor increase over minimal risk, commensurate experiences, and vital importance for the child's own disorder or condition; healthy children cannot be enrolled under 406
Assent may be waived when the child cannot be consulted or when direct benefit is available only in research
Permission may be waived under 46.408(c) for populations such as abused or neglected children, which is narrower than the general 46.116 waiver
Wards need an advocate for 406 and 407 research, not for 404 and 405
There is no Subpart E for adults with impaired capacity; Subpart E is IRB registration
Practice quiz
- Question 1Research involving children that presents greater than minimal risk with no prospect of direct benefit may be approved by the IRB under 46.406 only if the risk represents:
- Question 2Permission of both parents is required for research approved under:
- Question 3Under 45 CFR 46.402(b), which of the following constitutes assent?
- Question 4An advocate must be appointed for a child who is a ward when the research is approved under:
- Question 5Research not approvable under 46.404, 405, or 406 may proceed only after:
Recap
- Definitions: children by jurisdiction and procedure; assent is affirmative agreement; permission is the parent's or guardian's agreement; guardian is authorized for general medical care
- Four categories: 404 minimal risk, 405 direct benefit, 406 minor increase with three findings and both parents, 407 Secretary referral
- Assent and permission: capability by age, maturity, and state; waivers of assent; one or both parents; the 46.408(c) waiver for neglected or abused children
- Wards: advocate for 406 and 407 research
- FDA Subpart D parallels at 50.50 to 50.56 with a narrower permission waiver; other vulnerable groups under 46.111(b)
Coming next
Lesson 17, adverse events, unanticipated problems, and safety reporting.
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This course is for educational purposes only and is not legal, regulatory, or compliance advice. Regulations and guidance change, so confirm every requirement against the current eCFR text, OHRP and FDA guidance, and your institution's IRB policies before relying on it. CIP® is a registered certification mark of Public Responsibility in Medicine and Research (PRIM&R). This course is produced independently by Subthesis and is not affiliated with, endorsed by, or reviewed by PRIM&R or the CIP Council. The instructor is not a Certified IRB Professional. Completing this course does not confer CIP certification, satisfy CIP eligibility requirements, or count as CIP recertification continuing education.