Adults with Limited Capacity to Consent to Research

Question:

May a subject with worsening cognitive decline continue participation in a clinical trial when study drug administration is complete but follow up visits are ongoing?

– Principal Investigator, Research Institute

Response:

If a participant is no longer able to provide legally effective consent for themselves, the principal investigator needs to notify the IRB and the sponsor to determine if the subject may remain in the study. 

If the IRB determines that ongoing participation is permissible, the IRB will require consent by a LAR and may require assent by the participant (when feasible) to continue enrollment in the study.  The IRB will also determine how assent will be documented.

Brief Question:

Why does WCG IRB require assent from adults who lack decisional capacity when consent was already provided by a legally authorized representative (LAR)?

– Contract Regulatory Document Reviewer for a Pharmaceutical Company

Response:

Although the FDA regulations do not explicitly mandate the IRB to consider requiring assent from adults who lack the capacity to provide legally effective consent, there is support for this requirement in multiple regulatory frameworks. These frameworks include the guiding principles of the Belmont Report and FDA guidance on informed consent.

The Belmont Report states three basic ethical principles to guide IRB review of human subjects research. These principles are Respect for Persons, Beneficence, and Justice. The first principle of Respect for Persons advocates for two ethical convictions, “first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection.” The second conviction is addressed by requiring consent be obtained from a legally authorized representative whenever an adult subject lacks capacity to consent. The IRB acknowledges that decisional capacity is not a binary attribute. Subjects may fall along a spectrum of capacity and awareness. In order to ensure a subject’s autonomy is respected, the IRB requires investigators to obtain assent whenever a subject is capable of being reasonably consulted. 

The FDA states the following in a guidance document on informed consent:

IRBs and investigators should carefully consider whether the inclusion in research of individuals who lack consent capacity is ethically appropriate and scientifically necessary. Whenever individuals with impaired consent capacity (partial, fluctuating, or complete) are or may be enrolled in clinical studies, ethical and procedural challenges arise. Considerations that may help address these challenges, and provide additional safeguards, include:

Assessing whether individuals who cannot provide legally effective consent on their own behalf may nonetheless be able to provide some form of oral agreement (e.g., assent) at the outset of the study and, as appropriate, throughout the course of the research (e.g., for subjects with progressive disorders), and how such oral agreement would be documented. In such a circumstance, a legally authorized representative would need to provide documented written consent.

In conclusion, although the requirement for obtaining assent from adult subjects who lack the capacity to provide legally effective consent is not formally established in the federal regulations, WCG IRB has determined that this process is necessary to ensure respect for their autonomy.