Adults Who Lack Capacity to Consent to Research

Consent capacity refers to an adult’s ability to:

• Understand the purpose of the study
• Understand risks and potential benefits
• Understand alternatives to participation
• Understand the right to withdraw
• Make a voluntary decision

Certain neurological, psychiatric, or medical conditions may affect this ability.

NIH policy requires investigators to carefully justify and safeguard the enrollment of individuals who lack consent capacity.

In general, adults who cannot consent for themselves should not be enrolled unless:

• The research question cannot be answered without including them, or
• The study offers a sufficient prospect of direct benefit to justify the risks.

The NIH IRB will determine whether enrollment is approvable under one of the following categories:

Category A

Minimal risk research.

Category B

Greater than minimal risk with a prospect of direct benefit.

Category C

No more than a minor increase over minimal risk, no direct benefit, and no harm to rights, safety, or welfare.

Category D

Research that does not meet the above categories but has received additional review and approval by the NIH Institutional Official.

Research that anticipates enrolling adults who lack capacity cannot begin until IRB approval is obtained.

Investigators should consider whether participants have:

• Fluctuating capacity (e.g., certain psychiatric disorders)
• Progressive loss of capacity (e.g., neurodegenerative diseases)
• Permanent loss of capacity (e.g., advanced dementia or severe intellectual disability)

Your protocol must address how capacity may change over time.

If your study will enroll, or might enroll, adults who lack capacity, your protocol must:

• Clearly state that subjects without capacity may participate
• Provide scientific and ethical justification for inclusion
• Describe safeguards
• Describe any procedures that may be performed differently and/or not performed in this population
• Describe how capacity will be assessed initially and over time
• Explain how you will identify and confirm the Legally Authorized Representative (LAR)
• Describe how consent from the LAR will be obtained
• Describe how assent from the participant will be obtained, when possible. If assent will not be obtained, provide the justification for this.

If participants may lose capacity during the study, describe:

• How interim capacity assessments will occur
• Whether participants will remain in the study
• Under what conditions they will be withdrawn

Your protocol must describe:

• Who will assess capacity
• What tool or method will be used
• Where and when assessments will occur
• Whether assessments will be repeated

At the NIH Clinical Center, the Ability to Consent Assessment Team (ACAT) can conduct assessments. ACAT includes members from Psychiatry, the Human Subjects Protection Unit (HSPU), and Bioethics.

Capacity assessments may be required by the IRB or requested by the investigator.

If a participant lacks consent capacity and consent is required, consent must be obtained from a Legally Authorized Representative (LAR).

The LAR must:

• Be permitted under NIH Policy 403
• Have capacity to consent
• Be able to represent the participant’s wishes or best interests

Order of LAR at NIH Sites

1. Court-appointed guardian (authorized to consent to research)
2. Durable Power of Attorney (DPA) for health care
3. If no guardian or DPA:
   1. The participant may execute a DPA if capable
4. If no guardian or DPA and participant cannot execute one:
   1. Spouse or domestic partner
   2. Adult child
   3. Parent
   4. Adult sibling
   5. Other relative

Consult the NIH Office of General Counsel (OGC) if there are questions about the appropriate LAR. For subjects at the Clinical Center, see MAS 19-1 Determining Legally Authorized Representatives for Adult Patients Who Are Unable to Provide Informed Consent for Clinical Care or Re-Admission.

If a guardianship order exists, provide a copy to OGC.

If participants are expected to lose capacity during the study, consider asking them, while they still have capacity, to:

• Designate a surrogate decision-maker through a Durable Power of Attorney (DPA) for Health Care
• Complete the NIH Advance Directive for Health Care and Medical Research Participation (available through the Clinical Center Department of Bioethics)

This can help avoid disruptions if capacity is later lost.

Even when an LAR provides consent, the participant’s assent must be obtained unless the participant is unable to provide assent.

Assent:

• May be verbal or written
• Must be documented in the research or medical record
• Must reflect the participant’s affirmative agreement

If a participant is unable to provide assent, document this determination.

Your protocol must describe your assent plan.

If your study was not previously approved to include adults lacking capacity and a participant loses capacity:

Step 1

Identify and engage the LAR.

Step 2

Determine whether the loss of capacity is temporary or permanent.

If Temporary:

• No protocol modification is required.
• LAR consent is not required for continued participation.

If Permanent:

• Submit a protocol modification.
• Obtain IRB approval to include participants without capacity.
• The participant may remain enrolled while the IRB reviews the modification.
• If approved, obtain consent from the LAR.
• If not approved, withdraw the participant.

If the research involves only data or specimen analysis and no interaction or intervention, different considerations may apply.

The following resources are available at the NIH Clinical Center:

• Department of Bioethics – This service includes members trained in medical ethics and patient guidance.
• Human Subjects Protection Unit (HSPU) – Clinical Research Advocates. HSPU assesses and monitors NIMH participants, consults with researchers and the NIH IRB, and trains researchers in informed consent.
• Ability to Consent Assessment Team (ACAT) – Provides capacity assessments at the Clinical Center.

Investigators are encouraged to consult early when planning to enroll this population.

When enrolling adults who lack consent capacity:

• Inclusion must be scientifically and ethically justified.
• Risks must be appropriate to the regulatory category.
• Additional safeguards are required.
• Consent from an appropriate LAR is required (unless waived).
• Assent must be obtained when possible.
• Capacity must be reassessed when appropriate.

Recommendations from the Secretary’s Advisory Committee on Human Research Protections’ (SACHRP) Subcommittee on the Inclusion of Individuals with Impaired Decision-making in Research (SIIIDR)