240. Research Involving Adults with Impaired Decision-Making Capacity

Updated July 2, 2021

In general, all adults, regardless of diagnosis or condition, should be presumed competent to consent to participation in research unless there is evidence of serious disability that would impair reasoning or judgment. Although not specifically addressed in the regulations as a vulnerable population, the University IRB requires additional safeguards for research involving persons with decisional impairment. Psychiatric disorders (e.g., psychosis), developmental disorders (e.g., intellectual disability), and organic impairments (e.g., stroke, dementia) may be associated with diminished mental or emotional function, including capacity to consent to participate in research.

Scientifically and ethically appropriate research involving individuals with these, and other disorders is critical to illuminate the underlying mechanisms that lead to these conditions and to identify promising treatments. Such research must include individuals with severe and chronic forms of these disorders as well as those exhibiting minimal impairment. Researchers and the IRB must consider the degree to which these conditions may impair an individual’s capacity to consent to participation in research, including when decisional capacity may fluctuate over time and plan the research accordingly.

Investigators planning research in which adults with impaired decision-making capacity will be enrolled must provide the IRB with a:

scientific reason for involving this population in the research,
plan for assessing capacity to consent,
plan for obtaining surrogate consent (as appropriate),
plan to obtain participant assent (or description of why participant assent is not feasible), and
description of the procedures that are designed to minimize risks to participants.

Justification for Including Individuals with Impaired Decision-Making Capacity in Research

Individuals with impaired decision-making capacity may be enrolled in research only when their participation in the study is justified, capacity to consent is assessed and documented, and provisions for surrogate permission are in place (for participants who are incompetent).

For example, the IRB may require that researchers may only involve participants with impaired decision-making capacity under the following conditions:

individuals with impaired decision-making capacity comprise the only appropriate participant population;
the research question focuses on an issue unique to participants in this population; and
the research meets one of the following criteria:
- presents no greater than minimal risk to the involved participants;
- presents an increase over minimal risk to involved participants, but which offers the potential for direct individual benefit to the participant;
- presents a minor increase over minimal risk to involved participants and which does not have the potential for direct individual benefit; provided that the knowledge sought has direct relevance for understanding or eventually alleviating the participants' disorder or condition.

Rarely, research posing greater than minimal risk without the possibility beneficial interventions may be acceptable if the information sought is of vital importance for understanding or eventually alleviating the targeted disorder or condition.

Institutionalized populations may never be used as samples of convenience. Enrollment of institutionalized persons is only acceptable if:

voluntariness and competence can be assured, or
the research is directly related to the population’s condition and has the potential to benefit individual participants.

Assessing Capacity to Consent to Participation in Research

The capacity to consent of individuals with impaired decision-making capacity may be unknown. Researchers should not assume that a prospective participant is unable to provide consent. Rather, researchers should seek to objectively determine whether a prospective participant can provide informed consent.

The purpose of identifying individuals with impaired capacity to consent is not to exclude them from the research, but to seek ways to enable their participation in an ethically acceptable and compliant manner.

Research studies designed to involve individuals with impaired decision-making capacity must include:

a means to assess each potential participant’s capacity to provide consent,
the criteria for identifying individuals with diminished consent capacity, and
alternative methods for obtaining consent and assent for individuals with diminished consent capacity (when applicable).

The methods used to assess capacity to provide initial and continued consent must be commensurate with the level of risk to the participant, complexity of the research, and extent and duration of each participant’s involvement.

For research in which risk is minimal and participant involvement is limited, decision-making capacity may be assessed using less formal methods such as the professional judgment of a clinician or other individual with the appropriate training and expertise. The determination could be based on routine observation and interactions with a prospective participant.

Rigorous assessment methods (e.g., use of standardized instruments; evaluation by independent clinician or other qualified professional) would be required for participation in an investigational drug study or other research posing greater than minimal risk. Likewise, additional monitoring at specified study time points may be warranted when participants’ involvement is of long duration or when a new or different intervention arises during a research study (e.g., a biopsy or spinal tap).

Assessments of capacity to provide consent may be enhanced by the involvement of a consent monitor, participant advocate, or independent clinician.

Requirements for Assessing Capacity to Consent

PIs must ensure that the research team members responsible for assessing capacity to consent have the expertise necessary to accurately evaluate each prospective participant’s ability to:

act on hers/his/their own behalf;
comprehend the information presented (including the study purpose and procedures);
appreciate the consequences of participation as it relates to the hers/his/their own situation or health condition;
appreciate the consequences of alternatives to participation (when applicable); and
clearly communicate hers/his/their choice.

Fluctuating or Diminishing Capacity to Consent

For conditions in which decision-making capacity may fluctuate, PIs must include mechanisms to monitor the capacity of individual participants on an ongoing basis. PIs must also consider procedures to assure that participants’ rights and safety are continually protected such as adjusting the timing of study procedures to avoid periods of heightened vulnerability.

Assessing Understanding during the Consent Process

Researchers wishing to involve persons with impaired decision-making capacity in research have an ethical responsibility to assess prospective participants’ understanding of the proposed research.

Assessments in a minimal risk study could be as simple as a verbal interaction between the investigator and the potential participant. More complicated assessments could include administration of a formal assessment instrument or an independent clinical (interview-type) assessment, administered after the potential participant has been fully informed of the study.

Regardless of the strategy, the purpose of assessing understanding is to identify prospective participants that demonstrate sufficient recall and comprehension regarding their participation in the research study. The assessment method should allow for a repeat assessment or monitoring if the potential participant’s decisional impairment changes or is expected to change.

Open-ended questions are more likely to elicit useful information than questions requiring a simple yes or no answer. Researchers may consider the following questions to assess understanding:

We are inviting you to be in a research study. Do you have to be in the study?
What will happen if you agree to take part in this study?
What will happen if you decide not to be in the study?
What other care is available to you if you decide not to be in the study?
How might this study help you?
How might this study cause you harm?
What should you do if you agree to be in the study but want to stop later?
Who can you contact if you have a problem or question about the study?

Participant Assent

For research in which consent is obtained from a legally authorized representative, assent must also be sought when the individual is sufficiently capable of understanding her/his participation in a research study and of communicating. Where assent is a reasonable requirement, mere failure to object may not be construed as assent.

For research posing more than minimal risk, the objection of an adult participant who is incapable of consenting should be binding. However, the IRB may allow the adult participant’s objections to be overruled if one of the following is true:

the individual's participation is specifically authorized by a court of law, or
the intervention is available only in the context of the research and is expected to provide a direct health benefit to the participant.

The prospective or enrolled participant's objection to any aspect of the research at any time must be taken as a refusal or withdrawal of assent. For studies in which withdrawal requires continuation of some research interventions to protect participant safety and well-being (e.g., tapering of medication), the consequences of and procedures for early withdrawal should be explicitly stated in consent and assent documents.

Adjudicated Incompetence

Persons formally judged incompetent have a court-appointed guardian. Researchers must identify persons authorized to give legally valid consent on behalf of any individuals judged incapable of consenting on their own behalf and, at the same time, must abide by Nevada laws regarding surrogate consent (NRS 159.0805). Nevada law requires court approval before a guardian may consent to certain treatments or experiment involving a ward.

Considerations When No Legal Guardian Exists

Some individuals may be incompetent but not have a legal guardian. In these circumstances, researchers must request the individual’s family member seek a Court determination and appointment of a Guardian. A guardian with the Court’s approval may enroll the individual in the research study. PIs should seek counsel with Research Integrity staff or University Legal Counsel on how to proceed.

Vulnerability to Therapeutic Misconception

Individuals with impaired capacity to consent may be especially vulnerable to therapeutic misconception. Investigators must ensure participants and their families or caretakers are aware of the experimental nature of the research, including the uncertainty of benefits.

Additional Safeguards

For some research involving individuals with impaired decision-making capacity, additional safeguards may be advisable. For example, researchers and the IRB may consider using:

independent assessment of capacity to consent;
use of standardized instruments to assess capacity to consent;
independent clinician, monitors, or participant advocates during the consent process;
special techniques to deliver information to prospective and enrolled participants (e.g., story boards, video);
waiting periods to afford participants and their surrogates more time to decide about participation; and
psychological or medical screening criteria to prevent or reduce the chances of adverse reactions to therapeutic and research procedures.

Some interventional research may require consultation with participants’ health care providers to ensure that proposed research procedures will not be detrimental to ongoing therapeutic regimens.

IRB Review of Research Involving Individuals with Impaired Decision-Making Capacity

The University IRB includes members who are familiar with decision-making capacity impairments and will seek the expertise of qualified consultants when additional expertise is warranted.

In addition to confirming DHHS requirements for IRB approval are met, the IRB will assess the following:

justification for involving persons with impaired decision-making capacity in the research;
criteria for determining competence;
procedures for assessing consent capacity and participant’s understanding of the research;
procedures for identifying individuals who are legally authorized to consent on behalf of prospective participants who are unable to consent for themselves; and
procedures for obtaining participant assent.

The IRB may seek the advice of University Counsel to determine the applicability of state laws that might affect the participation of legally incompetent persons in research.

Re-reviewing research when an enrolled adult participant unexpectedly loses the capacity to consent

If a participant unexpectedly experiences a substantial impairment to his or her functional abilities that is not foreseeably temporary, researchers should notify the IRB. In such cases the IRB will determine whether it is necessary to re-evaluate the participant’s capacity to consent to determine whether the participant who has lost the capacity to consent is permitted to remain in the study. Re-review of research should use the same procedures as initial review.

If the participant is determined to be incapable of consenting and is not likely to regain the capacity to consent in the near future, but the convened IRB determines that his or her ongoing participation is reasonable, researchers should obtain his or her assent to continue enrollment (when feasible) and the consent of a legally authorized representative (LAR), as soon as possible.

If researchers or IRB members determine that it is necessary to withdraw the participant from the study, or from a component thereof, but the participant cannot be withdrawn for medical or safety reasons, he or she should be kept on the study intervention under compassionate use or off-label use, when possible.