Section XVII:

Special Requirements and Guidance for Investigators

WPP #: XVII-7

Title 7:

Evaluating Consent/ Persons with Limited Decision-Making Capacity

Effective Date:

01-30-08

Revision History:

12-06-04; 06-21-06

Objective

To provide guidance for investigators and the VCU IRB on the participation of persons, other than children, who may have impaired decision-making capacities.

Description

Individuals in a wide variety of situations may have impaired decision-making capacity. For example, temporary impairment may occur at times of physical trauma or emotional-stress. Chronically impaired decision-making capacity may or may not be present in individuals with neurologic, psychiatric, or substance abuse problems. Since important research questions may only be answered by studying persons with impaired decision-making capacity, precluding such individuals would deprive many from the potential benefits of medical science. The most severely impaired individuals have the greatest need for the benefits of research on etiology and treatment. Therefore, limiting research to the least impaired individuals would hamper research on the underlying causes and potential therapies of many disorders. As is true for almost all clinical research,such studies may not directly benefit the individual participant but may offer future benefits to others who have or will develop the condition or disorder. For example, genetic studies, biochemical measures,or other non-therapeutic approaches may benefit subsequent generations.

Unlike research involving children, prisoners, pregnant women, fetuses and neonates, no additional federal regulations specifically govern research involving persons whose decision making capacity is impaired. Importantly, while limited decision-making capacity should not prevent participation in research, additional scrutiny by IRBs and researchers is warranted for research involving this population.

  1. NIH Guidance:

    VCU makes every effort to review research involving persons who are or may be decisionally-impaired in accordance with the National Institutes of Health Office for Extramural Research guidance:

    1. Conflicting Roles and Potential Conflicts of Interest: Potential and actual research participants, especially those with permanent or transient cognitive impairments, may find it difficult to understand the difference between research and treatment, and to understand researchers' multiple roles, making "therapeutic misconceptions" particularly problematic, and possibly creating confusion among participants and their families.
      1. It is essential that the consent process (including consent documents) clearly indicate differences both between individualized treatment and research and between clinician and clinical investigator.
    2. IRB Membership: IRBs that regularly review research involving vulnerable subjects (such as the decisionally impaired) are required by DHHS and FDA regulations to consider including one or more individuals who are knowledgeable about and experienced in working with these subjects (45 CFR 46.107; 21 CFR 56.107). When reviewing research involving individuals with questionable capacity to consent, additional options in the makeup of the IRB should be considered:
      1. Include at least one voting member, independent of the research and investigators, with appropriate professional background, knowledge and experience in working with individuals with questionable decision making capacity;
      2. Include additional voting members from the community; these members may include representatives of patient advocacy groups and others not affiliated with the research institution.
    3. Assessing Capacity to Consent: Individuals’ capacities, impairments, and needs must be taken into account, in order to develop practical and ethical approaches to enable them to participate in research. Since well-validated and practical methods to assess capacity to consent are clearly needed, the NIH is supporting and will continue to support research addressing these issues. A clear understanding of the implications of various cognitive impairments, along with a careful consideration of proposed clinical research methodology, is required. Assessment is complex; simply answering a certain number of factual questions about a protocol may not be an adequate assessment of understanding. A key factor in participants' decision-making is their appreciation of how the risks, benefits, and alternatives to participation in the study apply to them personally.
      1. Limited decision-making capacity covers a broad spectrum. A healthy person in shock may be temporarily decisionally impaired. Another may be severely mentally retarded since birth. Persons with schizophrenia may have fluctuating capacity. Researchers should be sensitive to the differing levels of capacity and use assessment methods tailored to the specific situation. Further, researchers should carefully consider the timing of assessment to avoid periods of heightened vulnerability when individuals may not be able to provide valid informed consent.
      2. Both IRBs and clinical investigators must keep in mind that decision-making capacity may fluctuate, requiring ongoing assessment during the course of the research. The consent process should be ongoing.
    4. Responsibilities of Investigators and IRBs: Research projects proposing to involve persons with impaired decision making capacity should be approved by IRBs only after careful consideration, and indeed, some persons with impaired decision making capacity may need to be excluded from participation.
      1. Principal investigators and members of the research team bear primary responsibility for protecting research participants. Responsibilities of IRBs also are significant, including the review of the informed consent forms and processes and research design as presented in the research proposal. They should exercise heightened vigilance in the review of protocols involving individuals with questionable capacity in accordance with 45 CFR 46.111(b).
      2. As impairment increases, along with risks and discomforts, safeguards should increase according to a sliding scale, i.e., protections should be proportional to the severity of capacity impairment, or to the magnitude of experimental risk, or both. Provisions for additional safeguards should be in place prior to involving individuals with questionable decision-making capacity in research that poses greater than minimal risk.
      3. Educational efforts should be ongoing to enhance research participants' understanding and appreciation of their role in the research.
    5. Options for Additional Safeguards: A sliding scale involving assessment of risks, benefits, and capacity to consent should guide the IRB's decisions regarding additional safeguards. Many strategies are available as options for investigators as they develop their research protocols and for IRB members as they evaluate them. In considering increasing levels of risk and/or impairment, investigators should be creative in choosing appropriate protections, seeking strategies used successfully in other situations.
      1. Use of an Independent Monitor. When reviewing greater than minimal risk research involving individuals with questionable capacity to consent, IRBs should discuss and document the potential value of an independent monitor. A monitor can be appointed to be present when investigators invite individuals with impaired decision-making capacity to participate in a research study. The consent process should be visible throughout, and IRBs have a right to observe recruitment, assessment, the informed consent process, and debriefing of research participants (and/or their family/surrogates).
      2. Use of a Legally Authorized Representative (LAR). Where permitted by law, individuals with impaired capacity may have a family member or other legally authorized representative serve as a surrogate for research decisions, with this role documented during the consent process. (See WPP #XI-3 – Legally Authorized Representative – for the order of priority required in Virginia Code). Surrogates should be informed of the risks, benefits, and alternatives to the research when they are providing permission for an individual to participate. Whenever possible, surrogates should make research decisions based on substituted judgment, reflecting the views the individual expressed while fully capable. Best interest standards should be used if the values of the individual are not known. It is important that surrogates receive education about their own role, the cognitive and health status of the research participant, as well as about the study in which the participant may be involved.
      3. Use of Assent in Addition to LAR Permission. The limited or former autonomy of individuals with impaired decision-making capacity should be respected to the extent possible. Their assent to participation in research should be obtained whenever possible and their decision to withdraw from a study at any time should be honored. See WPP XV-2 - Assent and Informed Consent Considerations – for information about children’s assent and waiver of assent which may also be applied to adults with limited decision making capacity.
      4. Use of an Advance Directive. Where State or other applicable law permits, use of an advance directive for research may be considered.
      5. Use of Informational/Educational Techniques. Because informed consent is an ongoing process throughout the course of the protocol, assessing and enhancing comprehension at each stage is essential. Single sheet summaries of important information about key elements of a study may be useful when provided on a regular basis. Questions from potential participants and family members should be encouraged, and handouts of frequently asked questions and answers regarding specific human subject protections are recommended. Model consent forms and procedures can be developed. Communication between members of the research team and participants and their families is key to successful research participation.
      6. Use of Waiting Periods. Individuals who are decisionally impaired may need more time to consider the information they are given about a research protocol. Whenever possible, information should be provided incrementally to facilitate understanding. Planning built-in waiting periods within the consent process also may be useful to allow potential participants time to consult with family members about whether or not to participate.
      7. Request for Continued Participation. Investigators must indicate in their protocol conditions under which an LAR will be sought to give consent on behalf of a participant for research purposes, especially if not all eligible subjects will be expected to have the same level of decisional impairment. If the subject regains decision making capacity while the research remains active, the investigator is to inform the subject about his or her participation in a study and solicit the subject’s consent to continue participation. Such a request for continued participation may be incorporated onto the consent form that will initially be signed by the LAR. Alternatively, and preferably, the subject receives a different consent form that describes the initial involvement in the research and requests consent to continue participation. This document is reviewed and approved by the IRB prior to its use.
  2. VCU Evaluation Instrument:

    The VCU IRB provides a simple evaluation tool: VCU Informed Consent Evaluation Instrument. For research involving greater than minimal risk, this tool may be adapted and used by investigators on a voluntary basis for some or all research subjects as needed as part of the method for evaluating informed consent. In addition, the VCU IRB may require or recommend that investigators use or adapt this document or use some other form of evaluation, based upon the vulnerability of research subjects and the likelihood that some or all subjects may have limited decision-making capacities.

  3. VCU IRB Review Responsibilities

    In addition to NIH guidance provided above, and criteria for Legally Authorized Representatives as described in WPP XI-3 Legally Authorized Representative (Inclusion in Consent Process), the IRB should consider additional criteria to better protect the rights and welfare of decisionally impaired research subjects:

    • Does the research setting minimize fear or anxiety that may be experienced by decisionally impaired subjects?
    • Does the research allow subjects flexibility regarding timing of research interventions or interactions in order to minimize the perception of forced participation?
    • Do the research personnel have experience in working with persons who are mentally or cognitively impaired?
    • Does the research design seek to minimize exploitation of decisionally impaired individuals?
    • Are decisionally impaired subjects in a position to interact with known caretakers while the research is being conducted?
    • Should the decisionally impaired subject be provided with an advocate, separate from the LAR, for making decisions on the subject’s behalf?

Responsibility

It is the responsibility of the principal investigator to plan for ongoing informed consent of all research participants. It is the responsibility of the IRB to ensure that additional protections are in place and documented for research that is planned to include decisionally impaired persons.

References