ASSESSING EARLY ALZHEIMER AND AT-RISK GROUPS WITH PATIENT REPORTED OUTCOMES

描述（由申请人提供）：据估计，美国有530万人患有阿尔茨海默病（Alzheimer’s disease， AD），预计在未来几十年，受AD影响的人数和比例将迅速增长。阿尔茨海默症患者数量的显著增加已被认为是一种“流行病”，在发病早期就开始对个人和社会造成重大影响。近1000万美国人为患有阿尔茨海默氏症或其他痴呆症的人提供无偿护理，并且与家庭护理相关的高水平压力和负面健康结果已得到充分证明。据估计，这一人群的保健和长期护理服务费用是没有AD的老年人的三倍多。因此，对于阿尔茨海默病（AD）和其他痴呆症患者的药物和非药物治疗的比较有效性研究（CER）在医学研究所最近推荐的100个CER初始优先主题中排名第一就不足为奇了。我们的建议，重点关注轻度认知障碍，轻度/中度AD和AD高危患者的患者报告结果，是基于以患者为导向的结果的有效测量对CER的实施至关重要的前提。该提案建立在患者报告结果测量信息系统（PROMIS）的基础上，这是一个NIH路线图项目，旨在提高我们在广泛的慢性疾病和病症中测量患者报告症状的能力。PROMIS在多个领域的项目电池的开发和测试方面取得了重大进展。剩下的一个重要目标是评估PROMIS措施与常用（Legacy）措施的性能和研究效用。我们建议在300名患者中对两个现有的PROMIS域（身体功能和抑郁）进行验证研究，并通过在成人人群中首次评估PROMIS措施的代理反应（n=250）来扩展PROMIS的验证工作。我们之所以选择这两个结构域，是因为所有的PROMIS结构域都是AD和其他痴呆症中CER的核心。我们提出一个两阶段的项目。在第一阶段，一个专家小组将从广泛的物理功能PROMIS电池中选择最适合我们目标人群使用的产品。在第二阶段，我们将验证现有的物理功能和抑制PROMIS电池（PFDPB）在我们样本中的三个亚组内和跨组；通过比较受试者在两个时间点的PFDPB和Legacy测量，评估PFDPB和Legacy测量在每个亚组中检测有意义临床变化的相对能力；评估PFDPB在三个亚组内和跨三个时间点作为代理报告措施的潜在用途；并将模拟的基于计算机的PROMIS措施自适应测试与固定管理进行比较。项目结果将为研究人员评估维持或改善患者身心功能的药理学和非药理学干预的相对价值提供有价值和及时的信息。

DESCRIPTION (provided by applicant): It is estimated that 5.3 million Americans have Alzheimer's disease (AD), and that the number and proportion of Americans affected by AD is expected to grow rapidly in the next several decades. The striking increase in numbers of individuals with AD has been recognized as an "epidemic" with substantial personal and societal consequences which begin early on in the course of illness. Nearly 10 million Americans provide unpaid care for a person with AD or other dementia, and the high levels of stress and negative health outcomes associated with family care giving are well documented. Cost of health and long-term care services to this population are estimated to be over three times as high as those of elderly people without AD. It is therefore not surprising that Comparative Effectiveness Research (CER) on pharmacological and non- pharmacological treatments for individuals with Alzheimer's disease (AD) and other dementias ranks in the first quartile of the 100 Initial Priority Topics for CER recently recommended by the Institute of Medicine. Our proposal, focusing on patient reported outcomes in individuals with Mild Cognitive Impairment, mild/moderate AD and those at-risk for AD, is based on the premise that valid measurement of patient-oriented outcomes is essential to the conduct of CER. This proposal builds on the Patient Reported Outcomes Measure Information System (PROMIS), an NIH Roadmap project designed to improve our ability to measure patient-reported symptoms in a wide spectrum of chronic diseases and conditions. PROMIS has made significant strides in development and testing of item batteries across a wide range of domains. An important remaining goal is to assess the performance and research utility of the PROMIS measures against commonly used (Legacy) measures. We propose to conduct validation studies of two existing PROMIS domains (physical function and depression) in a well-characterized sample of 300 patients, and to extend the validation efforts of PROMIS by proposing the first evaluation of proxy response (n=250) to PROMIS measures in an adult population. We have chosen these two domains because of all PROMIS domains, they are central to the CER in AD and other dementias. We propose a two-phase project. In Phase 1, an expert panel will select items from the extensive physical function PROMIS battery that are most appropriate for use in our target population. In Phase 2, we will validate existing physical function and depression PROMIS batteries (PFDPB) within and across the three sub- groups in our sample; evaluate the relative ability of PFDPB and Legacy measures to detect meaningful clinical change in each sub-group by comparing PFDPB and Legacy measures in subjects at two time points; evaluate the potential use of PFDPB as proxy report measures within and across three sub-groups at two time points; and compare simulated computer-based adaptive testing of PROMIS measures to fixed administration. Project results will provide valuable and timely information to researchers assessing the relative value of pharmacological and non-pharmacological interventions for maintaining or improving patient physical and mental function. PUBLIC HEALTH RELEVANCE: This work will contribute to the success of Comparative Effectiveness Research involving individuals at risk for Alzheimer's disease (AD) as well as those already affected by it. By rigorously evaluating alternative measures of patient-reported outcomes in this population, it will provide valuable and timely information to researchers assessing the relative value of pharmacological and non-pharmacological interventions in maintaining or improving patient physical and mental function.