HRPP policies & procedures manual

502: Research involving human subjects unable to consent

1. Purpose

This policy describes the requirements designed to protect human subjects from exploitation and harm and, at the same time, make it possible to conduct essential research on problems that are unique to persons who are incompetent, or who have impaired decision-making capacity.

2. Policy

Research involving subjects who are mentally ill, or subjects with impaired decision-making capacity, warrants special attention. Research involving these populations frequently presents greater than minimal risk, may not offer direct medical benefit to the subject, and may include a research design that calls for washout, placebo, or symptom provocation. In addition, these populations are considered to be vulnerable to coercion. The investigator and IRB need to ensure that provisions are made to obtain legally effective informed consent prospectively from each research subject or permission from the subjects legally authorized representative (LAR).

3. Specific policies

3.1 Definitions

Surrogate consent

Obtaining from a surrogate decision maker (a person appointed to represent or act on behalf of another—legally authorized representative-LAR), the valid informed consent to participate in research for an adult subject who is cognitively impaired, lacks decision-making capacity, or suffers a serious or life-threatening disease.

Health care agent

The health care agent is the individual named in a durable power for health care decision maker (DPAHC) executed by the subject while the subject had decision-making capacity. The health care agent acts on the subject’s behalf to make health care decisions, including enrolling the subject in a research study, when the subject is unable to provide consent. A health care agent is considered a legally authorized representative.

Court-appointed guardian

A legal guardian is one who has been appointed by a court to make decisions for an individual who has been judicially judged to be incompetent. A courtappointed guardian is considered a legally authorized representative.

Legally authorized representative (LAR) as defined by FDA and DHHS regulations

An individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedures(s) involved in the research.

  • FDA regulations at 21 CFR 50.20 state that no investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative.
  • HHS regulations 45 CFR 46.116 state that if a subject is not legally competent to consent to participate in a study, the federal regulations require that a legally authorized representative consent for the subject.
Legally authorized representative in Washington

An LAR is one of the following, in order of priority:

  • designated proxy (such as a durable power of attorney for health care)
  • court-appointed guardian, or
  • next-of-kin

3.2 Investigator’s responsibilities

Investigators must apply to the IRB for use of surrogate consent that is specific to the particular study being reviewed.

  • Surrogate consent may be considered only in research studies relating to cognitive impairment, lack of decision-making capacity, or serious or life-threatening disease as conditions of the research.
  • Upon approval of the IRB for use within a specific protocol, the investigator shall apply the use of surrogate consent on a case-by-case basis.

If an adult subject is identified and is incompetent or lacks decision-making capacity for healthcare decisions and consent, the treating physician, the consulting physician(s), and others involved as members of the healthcare team must document in the medical record:

  • The basis for their determination that the patient lacks decision-making capacity.
  • The identity of the legal authorized representative and if none, the next-of-kin. (A copy of the legal form authorizing the durable power of attorney, etc. must be maintained in the research records.
  • The process by which the subject was enrolled or declined to be enrolled in the research.

3.3 IRB guidelines

Surrogate consent (using an LAR) is a protocol-specific request of the investigator, and must be reviewed and approved accordingly by the IRB:

  • Surrogate consent may be considered only in research studies relating to the cognitive impairment, lack of decision-making capacity, or serious or life-threatening disease and conditions of the research.
  • The IRB membership shall include at least one member who is familiar with the population to be recruited.
  • The IRB will consult the WSU AG office to determine that the appropriate LAR is used for the research study being reviewed. This includes any research conducted in another state.
  • The IRB shall utilize consultants as necessary to ensure appropriate expertise. Such consultants may not vote with the IRB or contribute to the quorum.
  • The IRB will consider whether and when to require a reassessment of the subject’s decision-making capacity, periodic re-consenting of the subjects, and the study’s renewal period.

3.4 Criteria for IRB approval

Incompetent persons or persons with impaired decision-making capacity are the only suitable research subjects.

Competent persons are not suitable for the proposed research.

The investigator must demonstrate to the IRB that there is a compelling reason to include incompetent individuals or persons with impaired decision-making capacity as subjects.

Incompetent persons or persons with impaired decision-making capacity must not be subjects in research simply because they are readily available.

Favorable risk/benefit ratio

The proposed research entails no significant risks, tangible or intangible; or, if the research presents some probability of harm, there must be at least a greater probability of direct benefit to the subject.

Incompetent people or persons with impaired decision-making capacity will not be subjects of research that imposes a risk of injury unless that research is intended to benefit that subject and the probability of benefit is greater than the probability of harm.

Voluntary participation

In situations where the potential research subject is incompetent to provide informed consent, the investigator should still attempt to obtain assent from the potential subject.

Some persons may resist participating in a research protocol that has been approved by their representatives.  Under no circumstances may subjects be forced or coerced to participate.

Well-informed representatives

Procedures have been devised to ensure that subject’s representatives are well informed regarding their roles and obligations to protect incompetent subjects or persons with impaired decision-making capacity. Health care agents (appointed under durable power of attorney for health care) and guardians must be given descriptions of both proposed research studies and the obligations of the person’s representatives. They must be told that their obligation is to try to determine what the subject would do if competent, or if the subject’s wishes cannot be determined, what they think is in the incompetent person’s best interest.

3.5 IRB determination and documentation

The IRB shall make a determination in writing of each of the criteria listed above. If these criteria are met, the IRB may approve the inclusion of incompetent subjects or subjects with impaired decision-making capacity in research projects on the basis of informed consent from legally authorized representatives or, if none exists, next-of-kin.

4. Applicable regulations and guidelines

45 CFR 46.111

45 CFR 46.116 and 46.117

38 CFR 16 and 17

Office for Human Research Protections (OHRP) guidance: Informed Consent, Legally Effective and Prospectively Obtained

5. Forms


6. Procedures employed to implement this policy & assignment of responsibility

IRB coordinatorProvide guidance to investigators as needed. Select appropriate primary and secondary reviewers. Obtain consult if needed.
Primary and secondary reviewers and tertiary reviewers Review study and determine if all safeguards are in place.
Determine if study meets criteria for using an LAR.