Research with Adult Individuals Lacking Consent Capacity

Capacity to consent exists when a subject demonstrates ability to:

• understand the nature of the research and of his/her participation;
• appreciate the consequences of the participation;
• show the ability to consider alternatives, including the option not to participate; and
• show the ability to make a reasoned choice. A “reasoned choice” should not be equated with the choice that would be considered “reasonable” by most people, but is simply a choice that has been considered by the individual and is logically consistent with that specific individual’s stated values.

Consent capacity is largely demonstrated by potential subjects’ ability to show understanding of the nature of the research and the research process; however, it should not be confused with the study team’s obligation to ensure that all subjects understand the research and are providing voluntary consent.

Lesser ability in one area does not preclude the study team from determining that a subject has capacity to consent. The study team makes this decision at their discretion and should consider the subject’s overall capacity based on these factors. It is important to note that capacity to consent does not equate to competency or even cognitive ability of a certain degree. For example, individuals who have a cognitive impairment such as slight dementia may, based on the factors above, have capacity to consent.

Study teams should also be careful not to equate physical incapacity with lack of capacity to consent. Potential subjects who retain consent capacity but lack ability to provide written signature should still provide consent and the study team should consider alternate mechanisms for allowing the subject to demonstrate their consent to participation.

The study team should present a plan for assessing potential subjects’ consent capacity when the target population includes individuals whose consent capacity is likely to be in question, for any reason. This includes individuals with any of the following conditions or disorders, among others:

• Under the influence of drugs or alcohol.
• Sedated or unresponsive
• Critical illness
• History of psychiatric illness or disorder
• Current psychotic event, especially if demonstrated by severe symptoms
• Traumatic brain injury or other acquired brain injury or disorder including potentially temporary conditions affecting brain function, such as delirium
• Dementia or other progressive brain disorder (e.g. Alzheimer’s Disease)
• Intellectual disabilities and/or developmental disorder

The plan for assessing capacity should include information on which individuals will be assessed, timing of assessment, and any tools which will be used to be assess capacity.

Which individuals will be assessed

The study team should present information to the IRB about which potential subjects will be assessed for capacity, including any presumptions the study team plans to make during recruitment. While many potential categories of subjects may be presumed to have capacity until the study team receives information otherwise, this may not be true for other categories of participants. For example, subjects who are sedated or unresponsive should be presumed to lack capacity and the IRB application may indicate that individuals will not be assessed based on this presumption and that a legally authorized representative will consent on their behalf.

Timing of assessment

For some subjects, consent capacity can vary from day to day or deteriorate over time. As such, consent capacity should be reassessed on a regular basis depending on changes in the underlying condition. If the subject no longer demonstrates consent capacity, the study team should take steps to obtain proxy consent for the subject’s participation going forward. Conversely if a subject who originally was unable to provide consent later regains consent capacity, consent should be obtained from the subject.

Assessment tools

The appropriate mechanism for conducting the assessment varies from study to study and should be based on several factors, including level of risk, potential for direct benefit to subjects, and the likelihood that potential subjects will have capacity. Informal approaches such as the teach-back method may be appropriate for studies which are easy to explain or which enroll subjects who are likely to have capacity. In this method, the study team asks potential subjects directed questions about the study in order to assess the potential subjects’ capacity based on the abilities described above. Questions might include:

• In your own words, can you tell me why you are doing this study?
• What will happen if you take part in this study? What will we ask you to do?
• Do you have a choice about taking part in this study?
• What are the risks of being in this study? What side effects might you experience?
• What are the benefits of being in this study?

Complicated clinical trials enrolling subjects whose capacities vary and which present greater than minimal risk to subjects may call for a more formal, intensive assessment mechanism such as the MacArthur Competence Assessment Tool for Clinical Research. Study teams should propose a mechanism they feel appropriate and allow the IRB to provide feedback during review. Cognitive assessments such as the mini-mental state examination (MMSE) are designed to assess cognitive function and should not be used as a stand-alone demonstration that consent capacity exists.

Informed consent must be obtained for the potential subject’s participation in the research. Only one person at any given time has legal standing to provide consent for a potential subject: a court-appointed guardian, the subject, or the subject’s legally authorized representative (LAR), in that order.

1. Guardian: If the potential subject has a court-appointed guardian who has been charged with making medical decisions for the potential subject, the potential subject cannot legally provide consent and/or HIPAA authorization for him/herself, regardless of the subject’s capacity to understand the research (similar to a parent consenting for a child).
2. Subject: If the study team determines the subject has consent capacity pursuant to the IRB-approved assessment procedures, the subject should consent/authorize for him/herself.
3. LAR: If the study team determines the subject does not have consent capacity pursuant to the IRB-approved assessment procedures, a legally authorized representative (LAR) must provide consent and/or HIPAA authorization for the subject's participation.  For research conducted within the state of Indiana, under Indiana Code 16-36-1-5, the following individuals may serve as an LAR in order of priority:
   
   1. Health care representative
   2. Spouse
   3. Adult child
   4. Parent
   5. Adult sibling
   6. Grandparent
   7. Adult grandchild
   8. The nearest other relative in the next degree of kinship not listed in items 3-7 above*
   9. The individual’s religious superior, if the individual is a member of a religious order*

If none of the above are reasonably available, the IRB may approve, on a case-by-case basis, that a friend may serve as LAR if the friend is an adult, has maintained regular contact with the individual, and is familiar with the individual’s activities, health, and religious or moral beliefs.  

*Individuals listed in #8 and 9 above may not serve as LAR if the research is subject to VA regulations.

The study team must take appropriate steps to identify the individual with the highest priority who is reasonably available to serve as the LAR, and should carefully document those steps in the research record. For more information regarding who should be considered reasonably available, see the IU HRPP Guidance on Informed Consent.

Requesting friends serve as LAR

While Indiana state law allows a friend to provide clinical consent for individuals who cannot consent for themselves, the IU HRPP believes the nature of research and the principles of the Belmont Report support allowing a friend to consent to another’s participation in research only in very specific circumstances. The IRB must approve a friend to serve as LAR on a subject-by-subject basis, based on specific justification from the study team explaining why allowing a friend to provide consent adequately protects the potential subject in the specific circumstances.

Example circumstances:

1. A subject has no spouse or relatives but has a committed partner to whom the subject is not married.
2. An elderly subject has no spouse or relatives but lives with a friend who provides companionship and emotional support.

The IRB will carefully the type of research, risk of research, and specific circumstances when determining whether friends should serve as LAR. If time is of the essence, study teams are encouraged to contact HRPP staff directly to discuss amendment submission requirements and timing.

When the IRB allows friends to serve as LAR, the study team is responsible for doing due diligence ensure and document that the friend has maintained regular contact with the individual, and is familiar with the individual’s activities, health, and religious or moral beliefs.

If the potential subject has a court-appointed guardian who has been charged with making medical decisions for the potential subject, the potential subject cannot legally provide consent or HIPAA authorization or him/herself, regardless of assessment.

Determining guardianship

If the subject population includes individuals for which there is reason to suspect that consent capacity and legal standing to provide consent could be in question, the study team must take prospective steps to determine whether the subject has a guardian. A review of medical records may not provide evidence of a guardianship so appropriate prospective steps should include (1) checking the Indiana Guardianship Registry available at https://public.courts.in.gov/GRP/ and (2) explaining guardianship to the potential subject and discussing whether one has been established for the individual. These steps should be completed during screening or pre-screening and should be a documented part of enrollment checklists.

Example questions include:

• Do you have a court-appointed or legal guardian?
• Is there someone who signs legal paperwork for you?
• Is there anyone else who should be involved in your decision making?
• Is there anyone who helps you make health care decisions?

The study team should listen carefully for any information which may indicate that a guardianship exists. For example, a subject with a guardian may be uncomfortable signing legal paperwork or may want to involve another person in the process.

If the subject indicates to the study team that a guardianship exists, or provides information during the consent process which may indicate that a guardianship exists, the study team should then ask about the circumstances of the guardianship to determine whether the guardian is required to consent to research on behalf of the potential subject. Indiana law allows for three types of guardianship:

• Guardian of the Person: oversees the proper living condition and treatment for the protected person.
• Guardian of the Estate: responsible to oversee and manage proper investment and financial affairs of the protected person.
• Guardian of the Person & Estate: responsible for both of the above aspects of a protected person’s life.

Only a guardian of the person would have authority to make medical decisions, including research participation.

If the potential subject has a guardian of the person, the study team also needs to know the scope of the guardianship. Indiana law allows for both full guardianship, in which the guardian is responsible for all legal decisions which need to be made for the protected person, and limited guardianship, which grants the guardian responsibility for specific decisions or types of decisions. For example, a limited guardian may be appointed to make financial decisions, medical decisions (including research participation), or even specific types of medical decisions, such as use of psychotropic medications.

In order to determine the type of guardianship, study teams should contact the person identified as the guardian for more information. If information provided by the subject or the identified guardian is unclear or confusing, the study team should request to see guardianship paperwork or contact additional interested parties, such as parents or spouses. In general, the HRPP expects that study teams would use a similar decision-making process as that used in clinical care.

When a potential subject has a guardian of the person which is applicable to research, the guardian must provide consent and HIPAA authorization for the potential subject. The potential subject should provide his/her permission, or assent, to participate in the research as well.

Post-enrollment considerations

If a subject provides consent for him/herself and the study team later determines that a relevant guardianship exists, the subject cannot continue in the study until the guardian provides consent for their continued participation. The subject’s participation until that time will not be considered serious noncompliance, assuming the study team took appropriate steps (pursuant to this guidance) to identify whether a guardian existed.

The guardian serves as the legal consent until the guardianship ends, meaning that the guardian must provide ongoing consent or authorization when required. If the guardianship ends while the subject is still participating in the research, the legal consent and HIPAA authorization for the subject’s participation ends and the study team should obtain consent and authorization from the research subject, if capable, or their legally authorized representative. If appropriate consent and/or authorization cannot be obtained, the subject must be safely withdrawn from the study.

Many protocols which involve subjects whose capacity may deteriorate over time utilize a dual-consent process in which the subject and their LAR both provide consent for the subject at initial enrollment. As described above, LARs should only provide consent when the study team has determined that the potential subject lacks capacity to consent, so a dual consent process is often counter to the regulatory requirements. However, the HRPP recognizes that having the LAR involved in the consent process from the beginning is advantageous. To that end, dual consent may be allowable when the study team expects that subjects may lose consent capacity during their participation.

• The IRB application should clearly describe the dual consent process and justify why a dual consent process is appropriate for the study.
• The potential subject should be informed that their LAR is providing their own consent for the subject’s participation in the event that the subject loses capacity and should help identify an appropriate LAR.
• Research records should clearly document how the LAR was identified and their relationship to the potential subject.
• If reconsent is required during the study, both the subject and the LAR should provide reconsent unless an assessment of capacity supports consent by one or the other.
  • If the study team assesses and documents that the subject has capacity to consent at the time of reconsent, the subject may consent without the LAR.
  • If the study team assesses and documents that the subject does NOT have capacity to consent at the time of reconsent, the LAR may consent without the subject.
• If the protocol requires the subject have capacity and retain capacity throughout their participation, dual consent is not acceptable.

When potential subjects cannot consent for themselves because they have a court-appointed guardian or lack capacity to consent, the potential subject should provide their permission, or assent, to participate in the research. Appropriate mechanisms for assent vary depending on the research. The study team should consider the complexity of the research and the ability of subjects to understand the information when proposing a mechanism for assent. The assent process may include one or more of the following mechanisms:

• Including the potential subject in the consent conversation with the guardian or LAR.
• Separate verbal conversation with the potential subject.
• Review of an assent document, pamphlet, video, or other tool which explains the study in language understandable to the potential subject.

Assent may not be practicable or appropriate in all situations, such as when the subject is on a ventilator, in a coma, or cannot otherwise participate in an assent process. In these situations, the study team should provide justification that assent will not be obtained in the IRB application.

Generally, when a subject expresses a wish to decline participation in research, the subject’s decision should prevail, even if his/her guardian or LAR has granted permission; however, unusual circumstances, such as potential for therapeutic benefit, may justify enrollment of the subject. If the investigator expects that subjects may express anxiety or dissent regarding participation in the research and may be enrolled regardless, justification should be provided in the IRB application.  

As in any area of compliance, complete and accurate documentation is key. Study teams should ensure that their research records include documentation which would allow an auditor to confirm that the study team conducted the assessment of capacity and obtained consent from the appropriate individual, including that the LAR is the highest priority available. The following provides guidelines for appropriate documentation for processes related to consent capacity.

Prior events in the national research community brought research with individuals admitted for inpatient or residential psychiatric treatment to the forefront of public debate.  Individuals admitted for psychiatric treatment may be particularly vulnerable to coercion or undue influence; as such, additional safeguards should be proposed by the study team and approved by the IRB to address this issue.  Appropriate safeguards vary depending on the research and the condition of the potential subjects but may include one or more of the following:

• Delay of research procedures, including recruitment and assessment for consent capacity, until the potential subject has been medically cleared or stabilized. In these situations, the attending physician should indicate that the potential subject is stable and it is acceptable to approach the potential subject. If the attending physician is also the investigator, a medical professional not involved in the research should assess the potential subject and provide their opinion.
• Assessment of consent capacity conducted by individual independent of the research.
• Inclusion of the medical director or other upline official in the consent process.
• Consent by members of the research team who are not participating in the subjects clinical care.
• Independent consent monitoring.
• Assent by the research subject.