Parental permission, child assent, and adolescent autonomy in clinical research

As a vulnerable population, children in general must rely on their parents or guardians to provide informed consent for them to participate in research. The assent of the child is obtained when the child is considered capable of providing it. Obtaining assent supports the child’s developing autonomy and allows them to participate as a partner in the research.

However, there may be situations where a general waiver of consent does not apply, but it may not be appropriate to obtain parental or guardian permission for the child to participate in research. Mechanisms under federal regulation and state law may be applied in these situations and depend on the agency (US Health and Human Services (HHS) vs US Food and Drug Administration (FDA)) that regulates the research.

The requirements

The requirements for parental permission and child assent are defined under HHS regulations, or the Common Rule, 45 CFR 46, subpart D, and under FDA regulations 21 CFR 50, subpart D. Parental permission must be obtained in compliance with those regulations for informed consent and there must be adequate provisions for obtaining the child’s assent. The child must provide affirmative assent, meaning that they need to actively agree to participate in the research. Mere failure to object to participation should not be considered to constitute assent.

But the level of understanding of the research when obtaining this agreement should consider the age, maturity, and psychological state of the child. The level of understanding does not need to meet the same standards required for an adult.¹ In fact, requiring such understanding would limit younger, less cognitively developed children from being able to participate in the consent process.

Waivers

FDA regulations are similar, but not completely analogous, to HHS regulations when it comes to waivers of informed consent and parental permission. The FDA recently adopted the waiver of informed consent for minimal risk research, when other conditions are met, that has always existed under HHS regulations. FDA allows waivers for the emergency use of a test article (21 CFR 50.23) and allows exception from informed consent for emergency research (21 CFR 50.24). HHS regulations allow for an exception from informed consent using the general provisions under 45 CFR 46.101(i).

Under HHS regulations, an additional waiver exists under 45 CFR 46.408(c) to allow the IRB to waive parental or guardian permission if it is not a reasonable requirement to protect the participants in the research, provided an appropriate mechanism for protecting the children is substituted and the waiver is consistent with Federal, state, or local law. The mechanism chosen to protect the participants depends on the nature and purpose of the research activities and the age, maturity, condition, and status of the children. Such waivers have been used when the parent or guardian’s knowledge of the research may result in harm or mistreatment of the child, or where the child may prefer to maintain confidentiality; for example, studies involving reproductive health issues.

The FDA did not adopt the waiver under 45 CFR 46.408(c). The rationale for not doing so was explained in the final rule to 21 CFR 50, subpart D.² In the final rule, the FDA stated that medical device regulations require that informed consent be obtained by each participant in a clinical trial of a device, except in certain, narrow emergency situations. A waiver of parental consent as contained in 45 CFR 46.408(c) would not be consistent with these regulations, since parental or guardian permission takes the place of informed consent when the participant is a child.

The final rule also notes that in situations where the child may want to maintain confidentiality, such as for the treatment of sexually transmitted diseases (STDs), that state law may grant certain classes of adolescents the right to act on their own behalf without parental consent. The FDA maintained that these laws would also allow adolescents to participate in research and consent for themselves, since they would no longer meet the definition of a child under the regulations.

Exceptions

There are a few situations where a minor can consent to their own healthcare and subsequently provide informed consent. These are condition specific situations, mature minor exceptions, and emancipated minor exceptions.³

Condition specific exceptions are situations where the adolescent can provide consent for healthcare needs related to sexual activity, treatment of STDs, contraception, mental health, and substance abuse. All states have laws that allow a minor of a specific age to receive treatment for STDs, and most states allow minors to consent for prenatal care, contraceptive services, and mental health services.^4,5,6 However, the age at which the minor can access these services independently can vary by state.^7,8 Most providers offer contraceptive services regardless of state law if the state allows the minor to consent for related services if the state law is unclear on this point.⁵

Mature minor exceptions are generally determined on a case-by-case basis, are specific to an individual child, and may apply to general healthcare, although, in some states, condition specific situations are considered under mature minor statutes. The age and applicability may vary by state and the status as a mature minor for an individual child may be established in a court of law. Status as an emancipated minor reflects the legal and social status of the minor, rather than the capability of the child. For example, “adolescents living separately from their parents and self-supporting, married, or on active duty with the armed forces are generally considered legally emancipated and able to provide informed consent or refusal for their own medical care.”³ Adolescent parents are generally considered emancipated to access and determine appropriate medical care for their children. Whether a minor is considered emancipated is also determined by state law.

IRBs

For studies where it may be important to respect the confidentiality and privacy of the child, such as studies on reproductive health, the Institutional Review Board (IRB) has the option to use the waiver under 45 CFR 46.408(c) for studies that either are reviewed under the Common Rule or are federally funded, but do not include an FDA regulated product. IRBs should consider this waiver to recognise the developing autonomy of the adolescent and respect the adolescent’s privacy, when appropriate.

For studies that are FDA regulated, that propose to enrol adolescents, the waiver under 45 CFR 46.408(c) cannot be applied. The responsibility for determining if the adolescent may sign an adult consent form under state law falls on the principal investigator (PI) at the study site or to those designated by the PI at the site who are authorised to consent participants for a study.

Because of varying laws across states, IRBs are not responsible for making these condition specific, general mature minor, or emancipated minor determinations. It is appropriate for PIs to allow adolescents to provide their own informed consent whenever state law allows them to do so for clinical care.