DiBenedetti Dana B, Menne Heather, Paulsen Russ, Krasa Holly B, Vradenburg George, Comer Meryl, Callahan Leigh F, Winfield John, Potashman Michele, Heithoff Kim, Hartry Ann, Oberdhan Dorothee, Wilson Hilary, Hoffman Deborah L, Wieberg Dan, Kremer Ian N, Taylor Geraldine A, Taylor James M, Lappin Debra, Martin Allison D, Hauber Brett, Romano Carla
Department of Patient-Centered Outcomes Assessment, RTI Health Solutions, 3040 Cornwallis Road, PO Box 12194, Research Triangle Park, NC, 27709-2194, USA.
RTI International, Research Triangle Park, NC, USA.
Neurol Ther. 2023 Apr;12(2):571-595. doi: 10.1007/s40120-023-00443-2. Epub 2023 Feb 15.
Insight into the relationship between concepts that matter to the people affected by Alzheimer's disease (AD) and the clinical outcome assessments (COAs) commonly used in AD clinical studies is limited. Phases 1 and 2 of the What Matters Most (WMM) study series identified and quantitatively confirmed 42 treatment-related outcomes that are important to people affected by AD.
We compared WMM concepts rated as "very important" or higher to items included in COAs used commonly in AD studies.
Twenty COAs designed to assess signs, symptoms, and impacts across the spectrum of AD were selected for review. Among these 20 COAs, only 5 reflected 12 or more WMM concepts [Integrated Alzheimer's Disease Rating Scale (iADRS), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory-Mild Cognitive Impairment (ADCS-ADL-MCI), Alzheimer's Disease Composite Scores (ADCOMS), and Clinical Dementia Rating; Clinical Dementia Rating-Sum of Boxes (CDR/CDR-SB)]. Multiple symptoms and impacts of AD identified as important and meaningful in the WMM studies map only indirectly at best to 7 of the 20 most widely used COAs.
While many frequently used COAs in AD capture some concepts identified as important to AD populations and their care partners, overlap between any single measure and the concepts that matter to people affected by AD is limited. The highest singly matched COA reflects fewer than half (45%) of WMM concepts. Use of multiple COAs expands coverage of meaningful concepts. Future research should explore the content validity of AD COAs planned for AD trials based on further confirmation of the ecological validity of the WMM items. This research should inform development and use of core outcome sets that capture WMM items and selection or development of new companion tools to fully demonstrate clinically meaningful outcomes spanning WMM.
对于那些受阿尔茨海默病（AD）影响的人而言，重要概念与AD临床研究中常用的临床结局评估（COA）之间关系的了解有限。“最重要的是什么”（WMM）研究系列的第1阶段和第2阶段确定并定量确认了42个对受AD影响的人来说很重要的与治疗相关的结局。
我们将被评为“非常重要”或更高等级的WMM概念与AD研究中常用的COA所包含的项目进行了比较。
选择了20个旨在评估AD各个方面体征、症状和影响的COA进行审查。在这20个COA中，只有5个反映了12个或更多的WMM概念[综合阿尔茨海默病评定量表（iADRS）、阿尔茨海默病协作研究-日常生活活动量表（ADCS-ADL）、阿尔茨海默病协作研究-轻度认知障碍日常生活活动量表（ADCS-ADL-MCI）、阿尔茨海默病综合评分（ADCOMS）以及临床痴呆评定量表；临床痴呆评定量表-框和总分（CDR/CDR-SB）]。在WMM研究中被确定为重要且有意义的AD多种症状和影响，充其量只是间接地映射到20个最广泛使用的COA中的7个。
虽然AD中许多常用的COA涵盖了一些被确定为对AD患者及其护理伙伴重要的概念，但任何单一测量方法与对受AD影响的人来说重要的概念之间的重叠有限。匹配度最高的单一COA反映的WMM概念不到一半（45%）。使用多种COA可扩大对有意义概念的覆盖范围。未来的研究应基于对WMM项目生态效度的进一步确认，探索计划用于AD试验的AD COA的内容效度。这项研究应为核心结局集的开发和使用提供信息，这些核心结局集应涵盖WMM项目，并为选择或开发新的配套工具提供信息，以充分展示跨越WMM的具有临床意义的结局。
