Northwestern University Clinical Outcome Assessment Team (NUCOAT)

西北大学临床结果评估小组 (NUCOAT)

• 批准号: 10475575
• 负责人: DAVID CELLA
• 金额: $ 84.89万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-10 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10475575
• 关键词: Northwestern; University; Clinical; Outcome; Assessment

We propose to develop and validate publicly available clinical outcome assessments (COAs) of physical function (PF) as they relate to a range of chronic conditions, fit for regulatory purpose. These COAs will assess PF as a patient-reported outcome (PRO) and a performance outcome (PerfO). The PRO and PerfO will be derived, and expanded as necessary, from publicly-available HealthMeasures (www.healthmeasures.net) assessments, including the Patient Reported Outcomes Measurement Information System (PROMIS), the NIH Toolbox for Assessment of Neurological and Behavioral Function (NIH Toolbox), and the Short Physical Performance Battery (SPPB), co-validated with accelerometer monitoring of physical activity. To validate COAs for use across the spectrum of physical function impairment, we propose 6 common conditions associated with sarcopenia and 5 rare disorders for consideration during the UG3 phase. In both cases (sarcopenia and rare disorders), we aim to sample the full range of PF impairment from mild to severe, and to sample different aspects of PF impairment as they affect different diagnostic groups. Our goal is to produce core PF outcome sets that can be applied broadly across the PF severity continuum for regulatory use in sarcopenia and rare disorders. In the UG3 planning phase, we will work with a broad range of stakeholders, experts, and the FDA, to identify target disease areas that are chronic, symptomatic, and have an impact on PF. The specific aims in this phase include (1) convening stakeholders, including patients, care partners, clinicians, measurement experts, payers, regulators, and pharmaceutical industry representatives, around the topic of PF related to approval of new drugs; (2) proposing model conditions in which to test measures of PF (e.g., rare diseases, sarcopenia), and identify potential gaps in our proposed PF measures; and (3) proposing plans for refining and testing. In the UH3 implementation phase, we will identify existing, revised, and newly developed assessment tools to be evaluated as COAs. Substantial COA core building blocks can be drawn from PROMIS and NIH Toolbox. These PF measures are appropriate for children and adults with a variety of chronic conditions and thus are ideal for deriving the cross-cutting COA core sets that the agency seeks to develop. We will then conduct the research required for validation, in accordance with FDA recommendations. The specific aims in this phase include (1) Produce a PF PRO, derived from mixed-methods research and the PROMIS PF bank v2.0, including short forms for mildly-, moderately-, and severely-impaired PF, and full-range PF; (2) Produce a PF Performance Outcome (PerfO), derived from the NIH Toolbox and the SPPB, optimized for responsiveness to conditions that affect PF; and (3) Validate the PF PRO and PerfO in three longitudinal studies: one addressing mild / moderate PF impairment, one addressing moderate / severe PF impairment, and one addressing a full range of PF impairment. This will produce publicly-available and accessible core clinical outcome sets for measuring physical function in pharmaceutical clinical trials, with the potential for widespread generalizability across conditions.

我们建议开发和验证公开的身体机能 (PF) 临床结果评估 (COA)，因为它们与一系列慢性病相关，适合监管目的。这些 COA 将评估 PF 作为患者报告结果 (PRO) 和表现结果 (PerfO)。 PRO 和 PerfO 将从公开的 HealthMeasures (www.healthmeasures.net) 评估中派生并根据需要进行扩展，包括患者报告结果测量信息系统 (PROMIS)、NIH 神经和行为功能评估工具箱 ( NIH 工具箱）和短身体表现电池（SPPB），与身体活动的加速度计监测共同验证。为了验证 COA 在各种身体功能损伤中的应用，我们提出了 6 种与肌少症相关的常见病症和 5 种罕见疾病，供 UG3 阶段考虑。在这两种情况（肌肉减少症和罕见疾病）中，我们的目标是对从轻度到严重的 PF 损伤的全部范围进行采样，并对 PF 损伤的不同方面进行采样，因为它们影响不同的诊断组。 我们的目标是产生核心 PF 结果集，可广泛应用于 PF 严重程度连续体，用于肌肉减少症和罕见疾病的监管。 在 UG3 规划阶段，我们将与广泛的利益相关者、专家和 FDA 合作，确定慢性、有症状并对 PF 产生影响的目标疾病领域。此阶段的具体目标包括（1）围绕与新药审批相关的 PF 主题，召集利益相关者，包括患者、护理合作伙伴、临床医生、测量专家、付款人、监管机构和制药行业代表； (2) 提出测试 PF 测量值的模型条件（例如，罕见疾病、肌肉减少症），并确定我们提出的 PF 测量值中的潜在差距； （三）提出完善和试验方案。 在 UH3 实施阶段，我们将确定现有的、修订的和新开发的评估工具作为 COA 进行评估。大量的 COA 核心构建模块可以从 PROMIS 和 NIH Toolbox 中获取。这些 PF 措施适用于患有各种慢性病的儿童和成人，因此非常适合得出该机构寻求开发的跨领域 COA 核心集。然后，我们将根据 FDA 的建议进行验证所需的研究。此阶段的具体目标包括 (1) 生成 PF PRO，源自混合方法研究和 PROMIS PF 库 v2.0，包括轻度、中度和严重受损 PF 的简写形式，以及全范围 PF PRO。 PF； (2) 产生 PF 绩效结果 (PerfO)，源自 NIH 工具箱和 SPPB，针对影响 PF 的条件的响应进行了优化； (3) 在三项纵向研究中验证 PF PRO 和 PerfO：一项针对轻度/中度 PF 损伤，一项针对中度/重度 PF 损伤，一项针对全方位 PF 损伤。这将产生公开可用的核心临床结果集，用于在药物临床试验中测量身体功能，并具有跨条件广泛推广的潜力。