Vulnerable Subjects - Cognitively Impaired
All adults (including those with cognitive impairments) are presumed competent to consent unless legally judged to be incompetent.
Cognitively impaired persons are considered a vulnerable research population because their mental disability may compromise their capacity to make a reasoned decision about participation in a study.
People with Alzheimer's disease, dementia, mental illness and developmental disabilities may be considered cognitively impaired and may not be able to provide informed consent for participation in research.
In certain circumstances, when it is determined that a potential research participant is cognitively impaired, federal regulations and state statute permit researchers to obtain consent from a legally-authorized representative via surrogate consent.
For research protocols involving subjects who have fluctuating or limited decision-making capacity or prospective incapacity, Principal Investigators should establish and maintain ongoing communication with involved caregivers, consistent with the subjects' autonomy and with medical confidentiality.
The National Bioethics Advisory Commission issued a report on Research Involving Persons with Mental Disorders That May Affect Decision-making Capacity (December 1998). The recommendations set forth in that report should be carefully reviewed by Principal Investigators considering research involving such a population. Some of the requirements or considerations discussed in the report include:
Determining Decision-Making Capacity
A primary consideration when recruiting subjects with severe cognitive or psychiatric disorders is to establish procedures for determining which individuals are able to provide legally valid consent, and which are not.
The protocol reviewed by the IRB must detail a specific plan for the assessment of the decision-making capacity of the subject. The assessment will be conducted by the investigator for any subject who may qualify for Surrogate Consent. While there are no standardized measures for determining capacity to consent, subjects may be assessed on their ability to understand and to express a reasoned choice concerning the:
- Nature of the research and the information relevant to his/her participation;
- Consequences of participation for the subject's own situation, especially concerning the subject's health condition; and
- Consequences of the alternatives to participation.
The capacity to understand all of these concepts may not be necessary in order to consent to participate in a particular research protocol -- greater capacity is required for higher-risk protocols. This assessment should be used for determining the capacity of the surrogate as well, if necessary.
In protocols in which surrogate consent has been approved by the IRB, assessment of the decision-making capacity of the surrogate should be implemented only when the investigator has reason to believe that the subject's decision-making capacity may be impaired.
Consent for Cognitively Impaired
To have the option to obtain consent from a subject's legally-authorized representative, the investigator must request the use of surrogate consent.
When consent will be obtained from a legally-authorized representative (surrogate), the IRB usually will require that the assent of the subject be obtained.
Assent is defined as affirmative agreement to participate in research. Failure to object does not qualify as assent.
For more information on the use of a legally-authorized representative, see Surrogate Consenrt.
Who/What is a Legally Authorized Representative?
"LAR means 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 procedure(s) involved in the research." 45CFR.46.102( c) and 21CFR50.3(l).
When is an LAR required?
An LAR is required in order to conduct human research in the Commonwealth of Virginia with a person who is an adult incapable of making an informed decision, as defined in Virginia Code 54.1-2982, at the time consent is required.
When such conditions are met:
- The person's legally authorized representative shall issue informed consent/permission and the signature shall be witnessed.
It is important to note that even though verbal consent, obtained over the phone may be obtained from the LAR for clinical care, verbal consent from the LAR is not allowed for research if written consent is required for the study.
- The research participant should be invited to participate in the informed consent discussion and provide his/her signature (as assent). (Exception see E5)
Minor. In Virginia, an individual below the age of 18 who is unemancipated is considered a "minor" for research purposes and must have a parent(s) or a legal guardian (either of which are considered Legally Authorized Representatives in Virginia) give permission for participation in research. The minor provides assent according to his or her capabilities. In cases where the child is under court-appointed or state custody a Legally-Authorized Representative, who is not the parent or legal guardian, provides consent on behalf of the child.
Who may be an LAR?
The list below indicates who may serve as LAR for an incapable adult in Virginia, in the following specified decreasing order of priority:
- the agent appointed under an advance directive, as defined in 54.1-2982, executed by the prospective subject, provided the advance directive authorizes the agent to make decisions regarding the prospective subject's participation in human research,
- the legal guardian of a prospective subject,
- the spouse of the prospective subject, except where a suit for divorce has been filed and the divorce decree is not yet final,
- an adult child of the prospective subject,
- a parent of the prospective subject when the subject is an adult,
- an adult brother or sister of the prospective subject, or
- any person or judicial or other body authorized by law or regulation to consent on behalf of a prospective subject to such subject's participation in the particular human research.
If a higher ranking LAR is identified after consent has been obtained, the higher ranking LAR must be contacted and informed of the study. He/she should be given a copy of the signed consent form and any communications with him/her should be documented in a note to file. A decision by a higher-ranking LAR to withdraw the subject from the research should be handled the same way one would handle a decision by the subject to withdraw if he/she becomes able to give consent for themselves. LARs and subjects considering withdrawal from a study should be fully informed about any clinical risks of withdrawing, such as feasibility, risks of removing inserted devices.
Federal regulations (HHS and FDA) offer the following broad definitions to which the above Virginia LAR list applies:
- "Parent" means a child's biological or adoptive parent.
- "Guardian" is "an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care" (45CFR46.402)
- FDA regulations further qualify the definition by adding that "for the purposes of subpart D of this Part, a guardian also means an individual who is authorized to consent on behalf of a child to participate in research." (21CFR50.3).
In the federal regulations, the terms 'parent' and 'guardian' specifically apply to those who are legally authorized to consent on behalf of a child. Note that in the case of a legal guardian, the child usually, but not always, lives with the guardian. Additionally, not every sibling in a family may have the same legal guardian.
Conditions Limiting LAR Use in Virginia:
- Unless the subject has been determined to be incompetent to provide consent for themselves.
- The IRB has approved the use of a legally authorized representative.
- to non-therapeutic research unless it is determined by the human research committee (IRB) that such non-therapeutic research will present no more than a minor increase over minimal risk to the human subject.
- to participation in human research on behalf of a prospective subject if the legally authorized representative knows, or upon reasonable inquiry ought to know, that any aspect of the human research protocol is contrary to the religious beliefs or basic values of the prospective subject, whether expressed orally or in writing.
- to participation in human research involving non-therapeutic sterilization, abortion, psychosurgery or admission for research purposes to a facility or hospital as defined by the Code of Virginia at 37.1-1.
- If participation in the research is protested by the prospective subject. In the case of persons suffering from organic brain diseases causing progressive deterioration of cognition for which there is no known cure or medically accepted treatment, the implementation of experimental courses of therapeutic treatment to which a legally authorized representative has given informed consent shall not constitute the use of force.
- If two or more persons who qualify as legally authorized representatives and have equal decision-making priority under this chapter inform the principal investigator or attending physician that they disagree as to participation of the prospective subject in human research, the subject shall not be enrolled in the human research that is the subject of the consent.
Use of LARs for research being conducted outside of Virginia
Different states may vary how they define:
- The age of children and/or minors, including emancipated minors,
- Which individuals can give permission for their participation in research and for the participation of children who are in court-appointed custody, and
- Which individuals are qualified to serve as legally authorized representatives.
Determinations about who can serve as an LAR, that is, consent on behalf of someone else's participation in research, are based on the jurisdiction in which the research is being conducted. The PI must understand the implications of state laws for the proposed research and describe how differing state requirements will be met in the research. Also note that research being conducted in foreign countries is subject to applicable laws for designating a legally authorized representative for the region or country in which the research is being conducted.
For research in which one or more eligible participants may require an LAR (as described in the protocol), the PI should cite, or provide an excerpt of, the relevant law regarding which individuals may serve as LARs for research being conducted outside of Virginia. The IRB reviewer may consult with the IRB Chair regarding the appropriateness of LAR eligibility for such research. General Counsel may also be asked to provide an opinion in this regard.
- If two or more persons who qualify as legally authorized representatives and have equal decision-making priority inform the principal investigator or attending physician that they disagree (with each other) as to participation of the prospective subject in human research, the subject shall not be enrolled in the human research that is the subject of the consent.
- No informed consent form shall include any language through which the person who is to be the human subject waives or appears to waive any of his legal rights, including any release of any individual, institution, or agency or any agents thereof from liability for negligence.
- Notwithstanding consent by a legally authorized representative, no person shall be forced to participate in any human research if the investigator conducting the human research knows that participation in the research is protested by the prospective subject.
- In the case of persons suffering from organic brain diseases causing progressive deterioration of cognition for which there is no known cure or medically accepted treatment, the implementation of experimental courses of therapeutic treatment to which a legally authorized representative has given informed consent shall not constitute the use of force, unless prior knowledge of participant refusal is known.
- Unless the research constitutes the best medical interests for the prospective participant and is not available outside of the research context, dissent or objection on the part of the participant ought to be respected regardless of the LAR's wishes.
IRB Considerations for Allowing an LAR to Provide Informed Consent on Behalf of a Decisionally Impaired Adult:
- The PI plans to/has requested to enroll adults who are not capable of providing consent.
- The PI indicates that an appropriate Legally Authorized Representative will be asked to give consent on behalf of the incapacitated adult.
- The PI indicates that all eligible subjects will require an LAR OR that some subjects may be able to provide assent or even consent for themselves
- The PI describes a plan and includes documents to assess capacity and solicit the consent for continued participation for adult subjects who will or may regain decision making capacity. Consider use or revision of the VCU Informed Consent Evaluation Tool here, as appropriate
- A written or script-supported consent document (or other information relevant to the research) will be provided to the research participant accompanied by a consent conversation, as applicable.
- The circumstances of the consent process provide the prospective participant or the LAR sufficient opportunity to consider whether to participate.
- The circumstances of the consent process minimize the possibility of coercion or undue influence.
- The person communicating information to the participant or the LAR during the consent process will provide that information in language understandable to the participant or the representative.