Question

Assent of Children and Adults with Cognitive Impairments

ICH (2016) E6 Section 4.8.12 requires that "when a clinical trial (therapeutic or non-therapeutic) includes subjects who can only be enrolled in the trial with the consent of the subject's legally acceptable representative (e.g., minors, or patients with severe dementia), the subject should be informed about the trial to the extent compatible with the subject's understanding and, if capable, the subject should assent, sign and personally date the written informed consent."
HHS regulations at 45 CFR 46, Subpart D (Protection of Human Subjects 2017) and FDA regulations at 21 CFR 50, Subpart D (Protection of Human Subjects 2016) require?

Answer 1

ICH E6, HHS, and FDA regulations require informed consent from a legally acceptable representative for minors and cognitively impaired individuals, and if possible, assent from the subjects themselves. This ensures respect for the subject's autonomy, comprehension of the risks, and voluntary participation. IRBs are responsible for maintaining these ethical standards in research involving human subjects.

Step-by-step explanation:

The regulations provided by ICH E6 Section 4.8.12 and the HHS and FDA require that individuals, including minors and those with cognitive impairments, are to be appropriately informed about a clinical trial to the extent that their understanding permits.

When such subjects cannot provide informed consent themselves due to their age or cognitive limitations, consent must be obtained from a legally acceptable representative, typically a parent or legal guardian. This legal consent does not negate the necessity for obtaining the individual's assent, to the greatest extent possible, which is an affirmative agreement to participate.

It is an ethical imperative to respect the principle of autonomy, ensuring that potential participants are provided with all relevant information regarding a study, making sure they understand the implications, risks, and benefits to facilitate a voluntary decision about their participation.

In addition, it is critical that informed consent documents are fully comprehensible and outline all potential risks and benefits, ensuring participants or their representatives are well-informed. Researchers must also avoid coercion, particularly when dealing with vulnerable populations, as it undermines autonomy and the ability to provide true informed consent.

All research must be approved by an Institutional Review Board (IRB), which verifies that informed consent processes are in place and ethical standards are maintained.