The study partner requirement in preclinical Alzheimers disease trials

项目摘要/摘要 阿尔茨海默病临床前临床试验招募认知正常的参与者，他们愿意接受 疾病生物标记物测试，了解结果，如果结果，则服用研究药物(或安慰剂) 表明他们罹患疾病的风险增加。就像阿尔茨海默病痴呆症的传统试验一样，这些 试验要求参与者注册一个研究伙伴，一个可以与参与者一起参加访问的人，以及 报告参与者的认知或功能能力的任何变化。就像阿尔茨海默氏症的传统试验 由于患有痴呆症，这些试验面临着与招募困难有关的后勤挑战。我们最近展示了 要求参与者了解他们的阿尔茨海默病生物标记物状态并不是阻碍 招聘成功。相比之下，与学习伙伴一起注册的要求是一个重要的障碍 许多潜在参与者的参与。我们还观察到的结果表明，研究伙伴 障碍与生物标志物检测和披露的要求有关。 该项目将进一步调查研究伙伴在阿尔茨海默病临床前试验中的作用。第一, 我们将探讨研究伙伴要求的伦理影响，特别是这一要求是否 注册的障碍，因为参与者不愿与其他人分享他们的生物标志物结果。第二, 我们通过测量告密者的准确性和精确度来检查研究伙伴的科学需求 评估认知表现，预测认知衰退，并认识到认知的细微变化， 并与参与者自己扮演这些角色的能力进行比较。 这些研究将为改进临床前AD试验方案设计提供有价值的数据，帮助 调查人员围绕1)是否需要研究伙伴，2)谁有资格担任这一角色， 以及3)应如何保护参与者免受与其资格相关的潜在污名。

Project Summary/Abstract Preclinical Alzheimer's disease clinical trials enroll cognitively normal participants who are willing to undergo disease biomarker testing, learn the results, and take an investigational drug (or placebo) if those results indicate that they are at increased risk for disease. Like traditional trials in Alzheimer's disease dementia, these trials require participants to enroll with a study partner, a person who can attend visits with the participant and report about any changes in the participant's cognitive or functional ability. Like traditional trials in Alzheimer's disease dementia, these trials face logistical challenges related to difficult recruitment. We recently showed that the requirement for a participant to learn their Alzheimer's disease biomarker status was not a barrier to successful recruitment. In contrast, the requirement of enrolling with a study partner was a significant barrier to participation for many potential enrollees. We also observed results that suggested that the study partner barrier was related to the requirement of biomarker testing and disclosure. This project will further investigate the study partner role in preclinical Alzheimer's disease clinical trials. First, we will explore the ethical implications of the study partner requirement, specifically whether this requirement is a barrier to enrollment because participants are unwilling to share their biomarker results with others. Second, we examine the scientific need for study partners, by measuring informants' accuracy and precision in assessing cognitive performance, predicting cognitive decline, and recognizing subtle changes in cognition, and comparing to participants' abilities to perform these roles themselves. These studies will provide valuable data toward improving preclinical AD trial protocol designs, assisting investigators making decisions around 1) whether to require study partners, 2) who is qualified to fill this role, and 3) how participants should be protected against potential stigma related to their eligibility.