Decisional capacity is critical for negotiating the world around us in active and meaningful ways that enhance independence and dignity. For those made vulnerable in late life by neurological and cardiac disease or mental illness that impacts cognition, or who have had lifelong intellectual disability and are now aging, the partial or total loss of decisional capacity is generally life changing. With research focused more on finding cures for some diseases and the development of both pharmacological and nonpharmacological treatments, older adults, particularly those with currently incurable diseases such as dementia, are being sought in increasing numbers to participate in research. In nursing research alone, the number of published studies focused on older adults has increased considerably in the past decade. As such, it is imperative that awareness be increased related to developments in both the ethical and regulatory aspects of decisional capacity assessment for research participation and the practical implications of both research programs and practices.
Society’s willingness to commit to research and investigators’ ability to continue to recruit robust samples of older adults rests largely on the level of public confidence with human research protections for its most vulnerable members. This capacity to recruit is critical in all research, with dementia research being a good example of where important new understandings hold the promise of preserving function and extending quality of life while the search for a cure continues. Yet this research also has the potential to exploit some of the most vulnerable individuals. The extent to which individuals with dementia are able to retain autonomy in regard to research participation, given the inevitable impact of the disease process on decisional capacity, and how society best protects these people from harm when their participation in research is sought are pressing social and ethical questions and a daily reality for investigators.
The purposes of this article are to briefly describe current understandings of the concept of decisional capacity specific to informed consent to participate in research for individuals with dementia, to describe recent developments related to the consideration by the Secretary’s Advisory Committee on Human Research Protections (SACHRP) of additional protections for decisionally impaired adult research participants, and to provide recommendations to help nurse investigators who work with older adults with potential decisional capacity impairment.
Defining Decisional Capacity
Capacity has been defined as performance on measures of decision-making ability (Karlawish, Casarett, & James, 2002). It is a crucial concept because, without it, the process of informed consent—the cornerstone of a moral and philosophical position on autonomy and individual choice in many Western societies—cannot occur as intended (Appelbaum, Lidz, & Meisel, 1989). Four abilities are widely acknowledged in the legal and bioethics communities as constituting legally competent decision-making capacity: understanding, appreciation, reasoning, and expressing a choice (Berg, Appelbaum, & Grisso, 1996; Grisso & Appelbaum, 1995; Marson, Earnst, Jamil, Bartolucci, & Harrell, 2000). It is important to be aware of what is intended to be conveyed by these single-descriptor abilities because each is complex in itself.
Understanding is the ability to comprehend information relevant to the decision and to be able to demonstrate that comprehension. Appreciation relates to the ability to apply this comprehension to one’s own situation. Reasoning refers to using the information to consider alternatives in light of consequences, and expressing a choice is related to the ability to communicate a decision to others (Berg et al., 1996; Henderson et al., 2006; Roth, Meisel, & Lidz, 1977; Tepper & Elwork, 1984).
Decision-making capacity is not correlated with age alone and is determined both by the preserved functional abilities of the individual and the complexity of the decisional task (Glass, 1997; Kim, Appelbaum, Jeste, & Olin, 2004; Kim, Karlawish, & Caine, 2002; Rabins, 1998; Roth et al., 1977). Further, consideration of characteristics of decision-making capacity, such as acute versus persistent impairment (e.g., pain versus traumatic brain injury), global versus specific impairment (e.g., sedation versus psychosis), and progressive versus fluctuating impairment (e.g., dementia versus mental illness), is instructive and extends understanding of the scope of the issue and the broad range of clinical and research situations in which capacity assessment underpins ethical behavior by researchers (Office for Human Research Protections [OHRP], 2007). The fact that decision making is a multidimensional capacity that is difficult to assess creates special challenges for both Institutional Review Boards (IRBs) adjudicating proposed research protocols and investigators recruiting for dementia-focused research.
Decisional Capacity for Treatment Versus Research Participation
There are important distinctions between the capacity for informed consent decision making related to treatment and capacity to consent to, or refuse, research participation (Appelbaum, 2007; Dunn & Jeste, 2001). Research informed consent arises in a research context and is subject to the oversight of IRBs. Research informed consent is receiving increased attention at both federal and state levels, but not all states have laws or regulations to address it or to permit surrogate (proxy) consent, although federal regulations provide for this option (Code of Federal Regulations [CFR] Title 45, 2005).
The risks and benefits of research participation may be different from those associated with treatment, especially with placebo assignment in some protocols. Prospective research participants must be clearly and fully apprised of risks and benefits, with an extent of disclosure that minimizes the possibility of them developing a therapeutic misconception; that is, underestimating risk and overestimating benefits associated with participation. This can occur when participants do not understand that the core purpose of clinical research is to produce generalizable knowledge, regardless of participant benefit (Appelbaum, Roth, & Lidz, 1982; Horng & Grady, 2003).
Research has demonstrated that misconceptions related to the potential benefits of research involvement are widely pervasive among research participants, particularly in clinical trials and in studies relating to gene therapies and other novel agents (Appelbaum, Lidz, & Grisso, 2004; Appelbaum & Roth, 1982; King et al., 2005; Lidz, Appelbaum, Grisso, & Renaud, 2004). Individuals with dementia, by the very nature of their disease, may be particularly vulnerable to therapeutic misconception, as may their caregivers and families. Both skill in the presentation of protocol-specific information and vigilance in the recognition of potential misunderstandings about what is possibly beneficial from participation are required of investigators.
Current U.S. Federal Regulations for the Protection of Human Subjects
Formal protection of vulnerable individuals from exploitation and harm in the research enterprise is a societal norm in the United States, enshrined in The Belmont Report (National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 1979) and expressed within the CFR Title 45, Part 46 (2005) and CFR Title 21, Part 50 (2005). Federal regulations require “legally effective informed consent” be given by research participants (CFR Title 45, 2005, §46.116) (Burgener & Berger, 2008). The regulations also permit consent by a legally authorized representative (LAR). However, no definition of who can fulfill this role is provided in the federal regulations; authority is delegated to the states. To date, few states have defined the LAR for research purposes, and the extent of the additional protections required when surrogate consent is used has not been determined.
Recent initiatives in several states (e.g., California, Virginia) demonstrate the complex legal terrain in this area, with neither state delineating essential safeguards for vulnerable participants (Kim & Karlawish, 2003). For the research community, this situation creates considerable concern, especially for investigators involved in recruitment for high-risk studies, longitudinal studies recruiting individuals with mild cognitive impairment (MCI) or early-stage dementia whose cognitive status will change in the course of the study, studies specifically recruiting participants because they are at high risk of developing dementia, and multisite studies recruiting from different states.
Dementia Diagnosis, Decisional Capacity, and Stigma
In the case of dementia, there remains a pervasive belief that, once diagnosed, a person with the disease is immediately and permanently rendered incapable of any level of independent decision making. Studies in several countries that have evaluated knowledge of Alzheimer’s disease (AD) during the past decade in both members of the general community and caregivers of individuals with dementia have shown widespread limitations in knowledge about the nature and impact of the disease, which potentially affect early diagnosis (Arai, Arai, & Zarit, 2006; Purandare, Luthra, Swarbrick, & Burns, 2007; Steckenrider, 1993; Sullivan, 2008; Werner, 2001; Werner & Heinik, 2008). In addition, this lack of knowledge of the disease process itself extends into a lack of knowledge about how dementia affects decision making and thus how decision-making capacity affects the process of informed consent for research participation. Concurrent with the wider social issue of dementia knowledge, important questions have been raised about the predictive accuracy of neuropsychological measures traditionally used by clinicians to assist in making judgments about the ability of individuals with dementia to independently perform a broad repertoire of activities of daily living. These questions extend to the issue of decisional capacity assessment, whom should be tested, how testing is most appropriately conducted, and how the results of testing can inform recruitment.
In the United States and other Western countries, despite more people being diagnosed much earlier in the disease process and concerted efforts in promoting awareness and acceptance by consumer organizations, the stigma of a dementia diagnosis—and the loss of personhood that is so readily and negatively associated with it—is acknowledged as potent and alienating by many individuals with the disease and their caregivers (Mackenzie, 2006; “Pratchett,” 2008; Vernooij-Dassen et al., 2005; Werner, 2001). This stigma can be explained, in part, by the fact that retention of decisional capacity is considered central to individuality and personhood in Western society and occurs in the presence of pernicious ageism that is difficult to combat.
The effect of labeling individuals with dementia as incapable of making their own decisions, removing from them an important aspect of the self, may be experienced negatively when they are aware of not having their choice heard or of their choice potentially being overridden in ways they may not be able to comprehend. The important provision of assent allows intent to be expressed and can be beneficial to individuals with dementia whose self-esteem may be diminished. However, requests for assent may also be stressful and impose additional burden without additional protection from harm.
While not completely contrary to pervasive stereotypes about what people with dementia can no longer do, the cognitive capacity reality is more complex, subtle, and construct specific. Although several studies suggest that individuals with early-stage dementia may have the capacity to provide informed consent for their participation in some kinds of protocols (Buckles et al., 2003; Resnick et al., 2007; Sugarman, McCrory, & Hubal, 1998), the general consensus is that early incapacity is the norm.
In a recent study, individuals with MCI performed differently on a measure of decisional capacity (MacCAT-CR) than their normal peers, and participants with MCI who were incapable of providing informed consent on a hypothetical complex clinical trial were found to be less educated (Jefferson et al., 2008). These results support the findings of an earlier study, which demonstrated that among patients with mild-to-moderate dementia, although fewer than 10% of those recruited initially had a clinically meaningful level of impaired consent to treatment capacity, as measured by the MacCAT-CR (Appelbaum & Grisso, 2001), more than one quarter of the sample (26.4%) developed issues within a year as compared with normal control participants (Moye, Karel, Gurrera, & Azar, 2006). A third study (Kim, Caine, Currier, Leibovici, & Ryan, 2001), also using the MacCAT-CR to assess decisional capacity for research consent (N = 37 patients with mild/moderate AD) and three expert clinicians as the criterion, found that 84% of the patients were incapable in at least one ability. Notably, clinicians’ ratings were higher, with 62% of patients incapable in at least one ability.
In a recent study of informed consent behaviors (N = 198 assisted living residents in 22 facilities), Mini-Mental State Examination (MMSE) (Folstein, Folstein, & McHugh, 1975) scores, instrumental activities of daily living scores, and dementia diagnosis were the best predictors of informed consent capacity. Considerably less than half (38%) of the participants were able to provide informed consent. This study shows the importance of considering decisional capacity assessment in high-risk populations and the importance of the availability of surrogate consent (Black et al., 2008). While surrogate consent is generally necessary, ethical aspects of surrogate-based research require further investigation.
Appropriate Use of Decisional Capacity Assessment for Research Participation
An important first question for investigators is “At what level of impaired decisional capacity is informed consent by the LAR warranted?” Clearly, if minimal or no residual capacity remains, no effective informed consent process can be undertaken with the person with dementia. Many investigators, to satisfy their local IRB and to feel a level of comfort in protecting the rights of the person with dementia with diminished capacity, routinely opt to use LAR-substituted judgment. In other words, investigator “safety” about providing adequate subject protection when decisional capacity is unclear is possibly a motivating factor.
In addition to LAR use, the person with dementia becomes involved in the decision making to the extent both that person and the LAR are comfortable. In reality, this may mean that the person with severe dementia merely sits in the room during the informed consent process, whereas for individuals with higher function, varying levels of explanation of the research protocol and their involvement in it are explained in simple terms. Scores on the MMSE are still widely used as a “barometer” of capacity, with scores less than 24 out of a possible 30 prompting use of an LAR. At least one study indicated that explanations of study procedures dominated most informed consent encounters with individuals with dementia, with less focus on the rights of the person to determine their involvement (Black, Kass, Fogarty, & Rabins, 2007).
Because the skilled assessment of decisional capacity is complex for the assessor, as well as likely stressful for the person with dementia, a reasonable determinant of the need to quantify capacity is the risk level of the protocol. Procedures delineated in the CFR Title 45, Part 46, Section 110 (2005) do not clearly determine minimal risk for decisionally impaired adults: CFR Title 45, Part 46, Section 102(i) recognizes the concept of indexing risk and gives the following guidance:
Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
Harms that would be considered minimal risk for participants with no decisional impairment may be more than minimal for a person with dementia and may cause distress.
The method used to assess capacity to consent needs to be commensurate with the level of risk to the participant and the complexity of the research. For minimal risk studies, it is arguable that formal decisional capacity assessment is not necessary. However, for studies involving greater than minimal risk, and for high-risk studies with limited or no benefit to the person with dementia, decisional capacity assessment is indicated and can be considered an ethical necessity. Yet, flexibility on the investigator’s part is essential because there is no universal assessment formula for all studies or for all potential participants in a given study.
Recent Developments Related to Federal Regulations and the Protection of Persons with Impaired Decision-Making Capacity
The group of people with decisional capacity impairment includes not only those with dementia but extends to any individual who is unconscious while undergoing surgery, has had a medical incident or accident affecting cognition, or has an intellectual or mental illness. Other vulnerable populations have historically been protected by U.S. federal regulations, for example children, pregnant women and fetuses, and prisoners. However, decisionally impaired individuals have not been specifically protected, although significant guidance has historically been provided by the OHRP and other entities to help IRBs and investigators (Beattie & VandenBosch, 2007).
In response to growing concerns about the rights and welfare of people with compromised capacity to make independent decisions relating to research participation, the SACHRP created the Subcommittee on Inclusion of Individuals with Impaired Decision-Making in Research (SIIIDR) in 2007. The charge of the subcommittee was to “develop recommendations for consideration by SACHRP about whether guidance and/or additional regulations are needed for research involving individuals with impaired decision-making capacity” (OHRP, 2007, Charge section). Specifically, this charge involved the SIIIDR reviewing Subpart A of CFR Title 45, Part 46 (2005) including the provisions at CFR Title 45, Part 46 Section 111(b) and CFR Title 21, Part 56 Section 111(b) for the U.S. Food and Drug Administration, applicable to this group. A call for public comment focused on a comprehensive set of questions relating to research with this group of people. After extensive deliberation, the report and draft recommendations of the expert committee were conveyed to SACHRP in mid-July 2008 (Strauss & Flynn, 2008).
The SIIIDR (Strauss & Flynn, 2008) primary draft recommendation is “that HHS [U.S. Department of Health and Human Services] develop a Subpart to 45CFR46 to include new regulations related to the inclusion of adults who lack consent capacity” (Recommendation VII). Further, the SIIIDR recommended specific actions for IRBs adjudicating research under Subpart A of CFR Title 45, Part 46 in relation to the determination of the LAR where there is no applicable state law (DeBarge, 2008). Changes to the regulations, if indeed the recommendations were acted on by the U.S. Department of Health and Human Services, involve a lengthy process that offers no immediate solutions to the pressing issues.
Instruments to Assess Aspects of Decisional Capacity for Research Participation in Individuals with Dementia
The capacity to make decisions in the context of treatment has traditionally been evaluated using clinical interviews, which have been demonstrated to be unreliable in some instances (Marson, McInturff, Hawkins, Bartolucci, & Harrell, 1997; Rutman & Silberfield, 1992). Clinical interviews, checklists, capacity measures, and capacity-sensitive neurological test batteries can all be used to determine capacity to give research informed consent. Training to assess specific abilities comprising capacity (as described above) has been demonstrated to improve interrater reliabilities in physician judgment in evaluating decisional capacity (Marson et al., 2000); however, no similar study has focused specifically on nurses’ skills in capacity assessment for research participation. Many tools are designed for administration by bachelor degree-level research assistants, but few instructions about training requirements are available (Jeste et al., 2007).
While the introduction of the MacCAT-CR (Appelbaum & Grisso, 2001), widely considered the most robust instrument available in this area, provided a means of assessing the four domains described above (understanding, appreciation, reasoning, and expressing a choice), there is still no agreed-on “gold standard” in the field. Now, a number of tools have been developed specifically for use with various patient groups, and at least one robust instrument review has been published (Dunn, Nowrangi, Palmer, Jeste, & Saks, 2006; Moye, Karel, Azar, & Gurrera, 2004). However, the systematic use of decisional capacity tools is a relatively new practice, and penetration into the field, including mandating by individual IRBs, has not gained momentum until recently. Considerable variability remains in the expectations of individual IRBs in this area and in the level of sophistication and understanding of decisional capacity assessment by investigators themselves. In addition, although a number of capacity constructs exist, greater empirical knowledge about clinical markers of capacity, clinical assessment, and areas of important intersections of law and clinical practice are needed (Moye & Marson, 2007).
Several new instruments have recently been published, including the University of California, San Diego, Brief Assessment of Capacity to Consent (UBACC) (Jeste et al., 2007) and the Evaluation to Sign Consent (ESC) (Resnick et al., 2007). The ESC is a promising 5-item scale with an additional unscored open-ended question and a 5-to-10-minute administration time. It is designed to assess whether the person with dementia has sufficient factual understanding to provide ethically valid informed consent for a specific research study, on the basis that previous research shows participants cannot correctly describe the research to which they are consenting (Resnick et al., 2007). The items assess participants’ ability to name at least two possible risks from participating in the study (Item 1), ask two things that will be expected from them as part of the study (Item 2), ask participants to describe what they will do if they no longer want to be in the study (Items 3 and 4), and ask them to explain the randomization process (Item 5).
The ESC was evaluated with participants enrolled in a randomized controlled trial testing a restorative care intervention (N = 346 nursing home residents from six U.S. facilities, mean age = 86.1) and is highly correlated with the MacCAT-CR. Interestingly, 218 participants did not pass the ESC, and although 80% could state what to do to withdraw, 50% could not name two things expected of them, and only 43% could explain treatment assignment (Resnick et al., 2007). What the availability of this information means in the context of study recruitment and what enhanced responsibility the investigator may have given this knowledge is unclear and remains one of the challenges of undertaking assessment.
Research Focused on the Decision-Making Competence of Individuals with Dementia
The science of decisional capacity has developed rapidly in the past decade. Significant attention has been given to articulating both the state of the science and an agenda to better protect the rights of individuals with decisional capacity limitations when they, or their LAR, are approached to give informed consent for research participation (Kim et al., 2004; Kim, Cox, & Caine, 2002; Kim, Karlawish, et al., 2002). The idea of a dichotomous reality—either one is capable of giving informed consent or one is not—is, fortunately, being eroded. Parameters of surrogate consent for both treatment and research in this population are being systematically evaluated, from the perspectives of the general community, caregivers, individuals with dementia, and people at high risk for developing dementia (Hopp, 2000; Jefferson et al., 2008; Stocking et al., 2008).
It is clear that any research about the informed consent process needs to take into account that clinical research with individuals with dementia involves a triad—the person with dementia, the LAR, and the investigator—embedded in the wider social context. However, concern for the protection of vulnerable individuals has already led to discourse about the need for independent advocacy for them in certain high-risk studies (Silber, 2008) and for more multifaceted approaches to enhance and extend protection in research, even when surrogate consent is used (Silverman, Luce, & Schwartz, 2004).
Recommendations for Nurse Investigators Working with Individuals with Dementia
Federal regulations stipulate that the investigator’s local IRB have a member with specific expertise in research with people with decisional capacity or be able to consult with such an expert when the IRB requires protocol-specific advice. This person is important to the investigator as a liaison with the IRB, with the capacity to explain aspects of the study protocol to other IRB members. The investigator should seek this person’s input when designing recruitment strategies and explaining how informed consent and assent will operate in the study. The clearer the protocol is and the more detail provided about additional measures the investigator will be taking to protect participants with decisional capacity issues, the easier the IRB’s job is in approving the protocol.
The investigator may ask to appear before the IRB to explain complex procedures and how he or she intends to safeguard the rights of vulnerable participants. The investigator may also need to consider serving on the IRB because he or she may, in fact, be the person with the most appropriate expertise in the institution’s research community, especially if the institution is small and has few investigators working in the area.
Investigators may question IRB decisions that seem to impose unreasonable burden on them, while not necessarily extending further protection to the people with dementia with whom they are working. Investigators may also find it helpful to network with others doing similar work so they are apprised of how IRBs in other institutions and entities are operationalizing federal regulations relevant to this group. This is a way to get a more comprehensive picture of where the investigator’s own institution sits along the continuum of responses and provides examples the investigator can use in discussion with the IRB.
Investigators need to be sensitive to the impact of additional procedures used to increase protection of individuals with dementia, while providing every opportunity for them to be involved in the informed consent process as much as they are able. The burden of what is being proposed in enhanced informed consent procedures must be considered related to the person with dementia.
It is also important to ensure the research staff are appropriately qualified, skilled, and experienced in the conduct of competency assessments in the absence of specific standards. Protocols in nurse-led research with individuals with dementia often focus on descriptive and exploratory studies of disease experience or on interventions to ameliorate distress, for example, relating to pain, incontinence, sleep disturbance, fatigue, and behavioral symptoms. In studies involving repeated measures within short time intervals (e.g., every 30 minutes), the IRB may require assent be obtained at the beginning of every observation period. This can be exhausting for the participant and the researcher alike and does not necessarily enhance protection, particularly when it is clear that the person with dementia is not capable of fully understanding why he or she is being asked to assent and to what. In these circumstances, it is useful to identify departures from behaviors characteristic of the individual that may indicate reluctance to participate (e.g., walking away, hiding, hand-wringing, crying). When behavioral changes that may be associated with the research protocol itself are identified, particularly with repeated requests for assent, it is important for the investigator to immediately discuss these with the LAR and seek input on the person’s continued enrollment.
Dyad recruitment of a person with dementia and his or her identified caregiver involves particular challenges because an aging caregiver, who may be the LAR, may also be decisionally impaired and thus not capable of acting in this role. Intact LAR decisional capacity underpins informed and appropriate access to the person with dementia. While no published study has yet examined decisional capacity in similar age LARs of individuals with dementia, anecdotal evidence suggests this is not uncommon. It is prudent to pay close attention to LAR capacity and, when necessary, consider recommending evaluation. Sound ethical and clinical judgment is required in deciding how to proceed in circumstances where it becomes clear that proceeding is not an option and that others, such as family members, may need to become involved.
Longitudinal studies, particularly greater than minimal risk studies involving individuals with MCI or very early-stage dementia, raise questions about changes in decisional capacity over the course of a study and how this can be handled within active protocols. Careful attention needs to be paid not only to if and how decisional capacity will be assessed on entry but whether or not it will need to be reassessed at meaningful intervals throughout the study. It has been suggested that arrangements made while a person is fully competent may be activated when his or her capacity diminishes; however, this is an area of law and ethics that is complex and still evolving. At this time, one cannot assume that advance directives are possible in all states and jurisdictions or will be explicitly followed where they do exist. Further, the issue of making an advance directive for future research involvement is fraught with ethical questions about how directives will be interpreted and acted on.
Nurse investigators must also consider the role their studies may play in contributing to knowledge about decisional capacity in individuals with dementia. The study by Jeste et al. (2003) is an example of collaborative work with this intentional goal.
The work of conducting research with vulnerable individuals with dementia demands deep commitment to ensure the quest for new knowledge does not overwhelm the rights of those it is intended to assist. Nurse researchers are well positioned to contribute to the discourse in this important area of research ethics.
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