Children, Assent and Undue Influence

Part of Human Subjects Protection for Clinical Research Staff: Vulnerable Populations and Undue Influence.

About 5 minutes. Free, in your language, no account needed.

Why this matters

Research with children needs two agreements: the child's and the parent's or guardian's. The rules name them differently, and the difference shapes what you do at the clinic desk.

ICH E6(R3) sets the international baseline for assent and the LAR's consent, covered at the end of this lesson. The detailed rules here are US law: HHS Subpart D (45 CFR 46) and the parallel FDA rules (21 CFR 50 Subpart D). Outside the United States, the legal age and permission rules come from national law and your ethics committee.

Who is a child, and what are assent and permission

In the United States, under Subpart D, children are persons who have not reached the legal age for consent to the treatments or procedures involved, under the law where the research is conducted (45 CFR 46.402(a)). Assent means a child's affirmative agreement. Mere failure to object should not be taken as assent when there is no affirmative agreement. Permission means the agreement of the parent or guardian (46.402).

Risk categories in Subpart D

Subpart D sorts research with children into categories (46.404 to 46.407). Each requires adequate provisions for assent and permission (46.408).

FDA's Subpart D (21 CFR 50.50 to 50.56) parallels these categories (50.51 to 50.54, with the Commissioner deciding research not otherwise approvable), plus permission and assent (50.55) and wards (50.56). The IRB or institution determines Subpart D compliance at initial review when children are subjects (21 CFR 56.109(h), 56.111(c)).

Assent and permission in detail

The IRB decides whether the children are capable of assenting, considering age, maturity and psychological state. Assent is not a necessary condition if the children cannot reasonably be consulted, or if the intervention offers a direct benefit important to health or well-being that is available only in the research. When assent is required, the IRB decides whether and how it is documented (46.408(a), (e)).

For permission, the IRB may find one parent's permission sufficient for research under 46.404 or 46.405. For 46.406 and 46.407, both parents must give permission unless one is deceased, unknown, incompetent or not reasonably available, or only one parent has legal responsibility for custody. For research HHS conducts or supports, the IRB may also waive parental permission for a population where it is not a reasonable requirement (for example, neglected or abused children) if an appropriate substitute mechanism is used and the waiver is consistent with law (46.408(c)). This waiver is HHS only. FDA's rule (21 CFR 50.55) has no parental permission waiver; it lets the IRB waive assent only, for a clinical investigation of no more than minimal risk (50.55(d)). In an FDA-regulated pediatric trial, expect parental permission to be required to the extent consent is required under 21 CFR 50 (50.55(e)).

Wards of the state or of other entities may be included in 46.406 or 46.407 research only if the research is related to their status as wards or takes place where most subjects are not wards. The IRB requires an advocate for each ward, independent of the research (46.409).

ICH E6(R3) says that when a minor is a participant, age-appropriate assent information is provided and discussed, and assent is obtained as appropriate (section 2.8.12). Consent should be considered if the minor reaches the age of legal consent. The IRB/IEC reviews the assent information with the age, maturity and psychological state of the minors in mind (1.2.7).

Undue influence

Consent must be sought under circumstances that minimize the possibility of coercion or undue influence (45 CFR 46.116(a)(2), 21 CFR 50.20). ICH E6(R3) says that neither the investigator nor site staff should coerce or unduly influence a participant to join or continue (2.8.3). The Declaration of Helsinki (paragraph 27) addresses dependent relationships. A child depends on adults, so watch your tone, timing and promises.

In practice

A research assistant at a pediatric clinic explains a study to a nine-year-old and her mother. She speaks to the girl directly, in plain words, and asks her to say back what will happen. The girl says she does not want the blood draw. The assistant does not treat the mother's permission as settling it. She tells the investigator and documents the girl's answer.

What this looks like when it goes wrong

A teenager is asked to join a study while his father waits next to him. The nurse says, "Your doctor would really like you to do this." The boy nods. The record shows permission and assent, but he agreed because the people he depends on wanted him to. The setting did not minimize pressure, and assent given under that pressure is not the affirmative agreement the rules are after.

Key takeaways