Use good clinical acumen when evaluating new drug therapy for older adults when this population is not representative of the study sample
If engaging in clinical research, adequately justify exclusion of subjects 75 years of age and older with comorbid conditions
Be aware of the challenges, and possible solutions, in research involving older adults
For potential research participants, assess decision-making capacity prior to obtaining informed consent, particularly in vulnerable populations
As there is currently no general consensus, be aware of laws regarding surrogate consent for research in the state in which you practice
Regarding surrogate consent, be aware of the ethical principles of substituted judgment, pure autonomy, and best interest for the older adult who lacks decision-making capacity
Encourage older adult to complete research advance directives to resolve potential ethical dilemmas
Informed Consent Issues in Geriatric Research
Informed consent is a process that is intended to ensure human research subjects are provided with the necessary information to make an informed decision to voluntarily participate in research. Agencies and regulations including the Food and Drug Administration (FDA), the Federal Policy for the Protection of Human Subjects (commonly called the Common Rule), the Office for Human Research Protections (OHRP), and the Institutional Review Boards (IRB) require informed consent for human research subjects in research studies. Based on ethical principles delineated in the Belmont Report, the informed consent process is intended to ensure that the autonomy of potential research subjects is protected by ensuring that they have decisional capacity and are free from coercion to participate [8].
Decisional Capacity
Decisional capacity is the ability to understand and process information and make judgments based on rational understanding of choosing one alternative instead of another [9, 10]. Hence, decisional capacity is the first requirement of informed consent. A consistent set of criteria for assessing decisional capacity has not been published; however, standards of incapacity include the inability to: express or communicate a preference or choice; understand one’s situation and its consequences; understand relevant information; give a rational reason, give risk- or benefit-related reasons, and/or to reach a reasonable decision [11]. Individuals who are capable of demonstrating understanding of the presented information, ability to reason, and consent or refusal to participate may be able to consent and participate in research.
Cognitively and mentally impaired persons are the most challenging to assess in terms of decisional capacity [12]. In some situations, individuals who are cognitively or mentally impaired have substantial impairment to decisional capacity, whereas in other situations individuals may be able to provide consent [13]. For example, older adults who are diagnosed with mental disorders, neurological disorders such as stroke and dementia, and metabolic disorders may retain decisional capacity, but these conditions can cause transient or persistent impairment in individual’s capacity to consent [13]. Not only can medical conditions affect decisional capacity, but the complexity of a research study may hinder the older person’s ability to fully comprehend the study and consent to participate [14]. For example, a potential subject may not be able to understand the implications of a randomized control drug trial, whereas they are able to understand and consent to a simple observational study [14]. Determining an individual’s capacity for consent and conveying information in an organized, understandable manner that allows for questioning and full consideration of all possible options are important ethical principles of the informed consent process [8].
Procedures for assessing decision-making capacity are defined by the research protocol and may include standardized and validated instruments with cutoff scores for participation, post-consent quizzes documenting the critical elements of the research, or alternative procedures [15]. Although decisional capacity is assessed during the recruitment and the enrollment phase of research, researchers must continue to assess for decisional capacity throughout the duration of the study. If participants lose the ability to consent after enrolling, the participation should be placed on hold for IRB review [16].
In the United States, additional protections of vulnerable research subjects are regulated by federal regulations and state statute. Federal regulations include cognitively impaired persons as “vulnerable” research populations that require additional consideration or protection. This may include individuals with Alzheimer’s disease, dementia, mental illness, and developmental disabilities [17]. Consequently, detailed procedures to determine decisional capacity and the ability to consent must be reviewed by the IRB when recruiting subjects with cognitive impairment [17].
Consensus is lacking on the degree of protection that should be afforded to individuals enrolled in surrogate-based research [18, 19]. In certain situations, federal regulations and state statute allow surrogate consent from a legally authorized representative. However, states define legally authorized representatives differently, and many states have no laws regarding surrogate consent for research [20]. Not surprisingly, the role of surrogate consent is contentious, and judgment on the part of all involved in conducting the research is required [21].
Competency
Although the terms are often used interchangeably, the legal concept of competency is not synonymous with decisional capacity. Competency refers to a court decision, usually by state probate court, which determines if an individual has the ability to make competent decisions [22]. In the case of an older person who is determined to be incompetent, a guardian (or conservator) may be appointed as the legally responsible decision-maker through the process of guardianship. The guardian is usually a family member, but can also be a court-appointed friend or impartial person [23]. Legal guardians have the authority to make decisions on behalf of the individual who was deemed incompetent, including participation in research as a legally authorized representative via surrogate consent. In situations where a guardianship is in place, obtaining proof of guardianship status and following strict research protocols to comply with guardianship requirements are important to conducting ethical research and protecting human subjects [23].
Surrogate Consent
Surrogate consent is based upon the ethical principles of substituted judgment, pure autonomy, and best interest standards of the research subject [24, 25]. According to the substituted judgment standard of surrogate consent, the exact preferences of the incapacitated person are unknown, and a surrogate determines these preferences based upon preexisting knowledge through understanding of the participant’s life history, values, and beliefs [25, 26]. The pure autonomy standard requires prior and formal prospective authorization of the incapacitated person to participate in research [25]. Lack of prior communication between an incapacitated person and a surrogate regarding the incapacitated person’s desire to participate in research is based upon the best interest principle whereby the surrogate makes decisions based upon what he/she judges to be the best for the incapacitated person [25, 27]. The best interest standard has been criticized in part because prior studies have demonstrated discordant judgments made by surrogates pertaining to an individual’s desire to participate in future research [18]. Without the pure autonomy standard of surrogate consent being met, the substituted judgment standard has been considered to be the only ethically permissible method of surrogate consent that demonstrates true respect [27].
The NIH and the National Bioethics Advisory Commission have proposed safeguards which are concomitant with the risk-benefit ratio. The required evidence from surrogate decision-makers increases as the risk-benefit ratio for the participant becomes less favorable. For example, in cases where research has the potential to directly benefit the subject, no positive evidence from the past is required as long as the research does not conflict with the person’s remaining preferences and interests. However, in cases of research studies that do not have a potential for direct benefit, it is suggested that participation be supported by positive evidence from the past [16]. When working with research participants who have diminished decisional capacity and require surrogate consent, researchers should respect the ethical framework laid out in the Belmont Report based on the tenets of respect, beneficence, and justice. Equal moral force of each principle is required to conduct ethical research, meaning that in certain situations, ethical principles will conflict and one principle should not outweigh another. In addition, from a practical perspective, researchers should clarify the current regulations and seek guidance from their IRB for each proposed research study to prevent adverse consequences for incapacitated adults [28].
Research Advance Directives
Bioethics researchers have maintained the best way to ensure respect for incapacitated participants (i.e., research participants with dementia) when subjects grant advance permission in a research advance directive [27]. However, few competent adults complete research advance directives, while the majority of those who do not complete research advance directives are willing to participate in research that may provide them with benefit [29]. As such, some researchers believe that requirement of formal research advance directives may hinder important research in dementia [29]. Suggestions have been made to develop advanced directives to encompass both medical and research directives and to require research advance directives for subjects who are competent, but at high risk for losing decisional capacity, such as individuals with mild Alzheimer’s disease who are enrolled in longitudinal studies [29].
Overcoming Challenges of Under-Recruitment of Older Adults in Research
Investigators are faced with many challenges in engaging older adults in clinical trials. One of the challenges is recruiting a homogenous sample to reduce confounding variables. However, older adults are a very heterogeneous sample, depending on the number and type of comorbid conditions, their cognitive and functional status, and whether they reside in the community or long-term care settings. Therefore, investigators need to simplify inclusion and exclusion criteria, but also include older adults from different ethnicities and lower socioeconomic classes to ensure the results are generalizable [30, 31]. High attrition rates, whether due to an acute hospitalization, loss to follow-up (i.e., relocated to long-term care), or death, present an additional challenge to the participation of older adults in research. Attrition rates have an effect on statistical power as well as generalization of study results. A suggested solution is to shorten the length of the study (i.e., 3–6 months versus 1–2 years), if possible, for interventional trials using study treatments [30]. A third challenge in enrolling large numbers of older adults in research studies is the consent process. Often, this process is too complex and time intensive secondary to the language level used and highly detailed explanation of the study protocol and risk-benefit ratio. One way to overcome this challenge is to use terminology at the fifth-grade education level which will benefit many older adults without a high school education. In addition, consent forms should detail only the essential components of the study, thereby reducing the amount of paperwork involved with the usual consent forms. If the older adult has impaired cognition, a legally authorized representative needs to be present during the consent process unless information is included in the older adult’s advanced directives stating a desire to participate in research. Investigators should detail this process for consenting subjects with cognitive impairment in the study design section of the proposal [32]. More detailed information on impaired cognition in research can be found elsewhere in this chapter.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
