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

描述(申请人提供)：据估计，有530万美国人患有阿尔茨海默病(AD)，预计未来几十年，受AD影响的美国人的数量和比例将迅速增长。阿尔茨海默病患者人数的显著增加被认为是一种具有重大个人和社会后果的“流行病”，在病程早期就开始了。近1000万美国人为阿尔茨海默病或其他痴呆症患者提供无偿护理，与家庭护理相关的高压力和负面健康后果是有据可查的。据估计，这些人口的健康和长期护理服务费用是没有老年痴呆症的老年人的三倍多。因此，毫不奇怪，关于阿尔茨海默病(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。我们的建议侧重于轻度认知障碍患者、轻度/中度AD患者和AD高危患者的患者报告结果，其前提是有效地衡量以患者为导向的结果对于进行CER至关重要。这项建议建立在患者报告结果衡量信息系统(PROIS)的基础上，这是NIH的一个路线图项目，旨在提高我们衡量患者报告的广泛疾病和状况的症状的能力。Promis在广泛领域的项目电池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措施相对于常用(传统)措施的绩效和研究效用。我们建议对现有的两个PROMIS领域(身体功能和抑郁)在300名患者中进行验证研究，并通过在成人人群中提出对PROMIS措施的代理反应(n=250)的第一次评估来扩大PROMIS的验证努力。我们之所以选择这两个结构域，是因为所有的Promis结构域，它们是AD和其他痴呆的CER的中心。我们提出了一个分两个阶段的项目。在第一阶段，一个专家小组将从广泛的身体功能PROMIS电池中选择最适合我们目标人群使用的项目。在第二阶段，我们将验证我们样本中三个子组内和跨三个子组的现有身体功能和抑郁Promis电池(PFDPB)；通过比较受试者在两个时间点的PFDPB和Legacy测量，评估PFDPB和Legacy测量在每个子组中检测有意义的临床变化的相对能力；评估PFDPB作为代理报告测量在三个子组内和跨三个子组在两个时间点的潜在使用；以及比较Promis测量的模拟计算机适应性测试与固定给药。项目成果将为评估药物干预和非药物干预在维持或改善患者身体和心理功能方面的相对价值的研究人员提供宝贵和及时的信息。 公共卫生相关性：这项工作将有助于比较有效性研究的成功，该研究涉及阿尔茨海默病(AD)的风险个人以及那些已经受到该疾病影响的人。通过严格评估患者报告结果的替代指标，它将为评估药物干预和非药物干预在维持或改善患者身心功能方面的相对价值的研究人员提供宝贵和及时的信息。

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.