Development of a Qualification Plan for an Activity Monitor-Based Endpoint Measure in Chronic Heart Failure (DDT COA #000114)

摘要 慢性心力衰竭（CHF）是当心脏不能泵送足够的血液以满足心脏的需要时产生的。 身体的需要。美国约有650万人， 全世界都有心力衰竭。特定CHF症状，如呼吸短促、胸痛， 和疲劳是导致活动减少和日常活动能力受限的因素 活动因此，结合对患者报告的症状和影响的评估， 对于CHF，监管机构和申办者已经表达了对日常活动新措施的兴趣， 利用可穿戴设备。为了帮助解决这一衡量机会， 该小组提出的基于活动监测的终点测量被中心接受， 2019年5月3日，药物评价和研究的COA认证计划（DDT #000114）。它 旨在评估客观测量的身体活动的各个方面，这些方面反映了一个人 CHF进行有意义的日常活动的能力。为了进一步进行鉴定工作， 建议的项目将导致资格计划（QP）的制定和提交。 进行了一项概念启发研究，以产生关于日常生活的定性证据。 为CHF患者的生活带来目的和意义的日常体育活动。 经常报告的活动涉及轻度至中度体力活动（例如，打扫，做饭， 洗衣服和园艺）和散步（例如，购物和约会）。的 下一步将是成立一个咨询小组，由具有以下方面专门知识的个人组成： 识别有临床意义的活动监测结果，以审查定性 研究结果并就现有（或提议的新）活动监测指标达成共识 最能反映/捕捉这些活动所代表的健康的有意义的方面。一旦 就有待进一步评价的基于具体活动监测器的衡量标准达成一致，我们 将继续开发QP。编制的QP将解决CHF工作 小组的研究计划，以产生必要的定量证据， 用于CHF药物开发的基于活性监测的终点指标的确认。 我们的方法包括两个目标：（1）召集一个顾问小组， 关于定性研究的结果，并就特定活动监测器达成共识 将成为QP重点的指标，以及（2）准备并提交活动的QP 基于监测的终点测量。这个项目的长期结果将是一个合格的，公开的 可用的基于活动监测的终点测量，这将填补评估中的一个关键空白 在CHF治疗试验中进行身体活动，以获得新兴的创新疗法。

ABSTRACT Chronic heart failure (CHF) results when the heart cannot pump enough blood to meet the body’s needs. Approximately 6.5 million people in the United States and 26 million people worldwide have heart failure. Specific CHF symptoms, such as shortness of breath, chest pain, and fatigue, are contributing factors to reduced activity and limitations in ability to perform daily activities. Hence, in conjunction with the assessment of patient-reported symptoms and impacts of CHF, regulators and sponsors have expressed interest in novel measures of daily activity that leverage wearable devices. To help address this measurement opportunity, the CHF Working Group’s proposed activity monitor-based endpoint measure was accepted into the Center for Drug Evaluation and Research’s COA Qualification Program (DDT #000114) on May 3, 2019. It is intended to assess aspects of objectively measured physical activity that reflect a person with CHF’s ability to perform meaningful daily activities. To further this qualification effort, the proposed project will result in the development and submission of a Qualification Plan (QP). A concept elicitation study was conducted to generate qualitative evidence regarding the day-to- day physical activities that bring purpose and meaning to the lives of persons with CHF. Activities frequently reported involved light to moderate physical activity (e.g., cleaning, cooking, doing laundry, and gardening) and walking (e.g., shopping and going to appointments). The next step will be to form an advisory panel, composed of individuals with expertise in the identification of clinically meaningful activity monitor-based outcomes, to review the qualitative study findings and gain consensus on the existing (or proposed novel) activity monitor metric(s) that best reflect/capture the meaningful aspect of health represented by these activities. Once there is agreement on the specific activity monitor-based metric(s) to be evaluated further, we will proceed with development of the QP. The compiled QP will address the CHF Working Group’s research plan for generating the quantitative evidence necessary to support qualification of the activity monitor-based endpoint measure for use in CHF drug development. Our approach includes two aims: (1) convene an advisory panel to provide critical input regarding the results of the qualitative study and gain consensus on the specific activity monitor metric(s) that will be the focus of the QP, and (2) prepare and submit a QP for the activity monitor-based endpoint measure. The long-term result of this project will be a qualified, publicly available activity monitor-based endpoint measure, which will fill a critical gap in the assessment of physical activity in CHF treatment trials for emerging innovative therapies.