Proxy Decision Making for Alzheimer Disease Research

描述(申请人提供)：开发有效治疗阿尔茨海默病(AD)的希望寄托在临床研究上，这将不可避免地需要招募AD患者，其中许多人缺乏同意研究的能力。因此，AD研究人员在征得病人同意的同时，还必须经常依靠代理人同意。因此，AD研究的道德完整性高度依赖于代理同意。然而，关于哪些因素影响代理人关于招募亲属的决定，代理人如何评估风险和收益，以及哪些因素影响他们对研究方案的理解，人们知之甚少。这项拟议的工作与一个重点但关键的问题有关：代理如何就不同风险和收益水平的协议做出决定？很少有实证研究使用系统多样的、现实的协议作为刺激来研究代理决策。通过仔细控制刺激方案并衡量对代理决策的各种潜在影响，我们将提供有关代理同意的重要经验性信息。我们将随机分配200名AD代理决策者，以获得对四种假想的AD药理学研究方案之一的同意，这些方案根据潜在风险水平和直接患者受益的潜力而有系统地变化。目的包括：(1)确定对代理人的研究决策和对AD研究的感知的影响，包括感知的风险和收益；(2)检查对代理人本身决策能力的潜在影响。此外，我们将评估几个探索性目标，包括：检查一系列对代理人登记亲属意愿的潜在影响以及他们对礼仪风险和好处的看法，包括照顾者负担和抑郁、患者疾病严重程度、代理人/患者关系、性别和种族的可能角色；研究专家定义的风险和利益水平与代理人的看法之间的一致性；以及探索代理人如何概念化决策任务以及代理人作为决策者的感受。标量问题和开放式问题都将被用来生成一个丰富的数据集，重点是开发一个细微差别的背景框架，以理解代理决策。这项研究具有很高的公共卫生和生物伦理学意义，因为它将解决对AD患者在重要临床研究中进行伦理招募至关重要的问题，但目前几乎没有经验数据来指导研究实践或政策。

DESCRIPTION (provided by applicant): Hopes for developing effective treatments for Alzheimer disease (AD) rest on clinical research, which will, by necessity, need to enroll AD patients, many of whom lack capacity to consent to research. AD researchers therefore must often rely on proxy consent alongside patient assent. The ethical integrity of AD research is thus highly dependent on proxy consent. Yet, very little is known about what factors influence proxies' decisions about enrolling their relatives, how proxies evaluate risks and benefits, and what factors influence their understanding of research protocols. This proposed work pertains to a focused, yet critical question: how do proxies make decisions about protocols of varying risk and benefit levels? Few empirical studies have used systematically varied, realistic protocols as stimuli to study proxy decision making. By carefully controlling the stimulus protocols and measuring a variety of potential influences on proxy decision making, we will provide important empirically grounded information regarding proxy consent. We will randomly assign 200 AD proxy decision makers to receive consent for one of four hypothetical AD pharmacologic research protocols, systematically varied by level of potential risk and potential for direct patient benefit. Aims include: (1) to determine influences on proxies' research decisions and perceptions of AD research, including perceived risks and benefits; and (2) to examine potential influences on the decision making abilities of the proxies themselves. In addition, we will evaluate several exploratory aims, including: examining an array of potential influences on proxies' willingness to enroll their relative and their perceptions of protocol risks and benefits, including the possible roles of caregiver burden and depression, patient illness severity, proxy/patient relationship, gender, and ethnicity; studying concordance between expert-defined levels of risk and benefit and proxies' perceptions; and exploring how proxies conceptualize the decision-making task as well as how proxies feel about serving as decision makers. Both scalar and open-ended questions will be used to generate a rich dataset focused on developing a nuanced contextual framework for understanding proxy decision making. This research has high public health and bioethical significance, as it will address issues that are fundamental to ethical enrollment of AD patients in vital clinical research, but for which little empirical data currently exist to guide research practice or policy.