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与一系列慢性条件相关的身体机能（PF）公开临床结果评估（COA），适合调节目的。这些COA将评估PF作为患者报告的结果（PRO）和性能结果（Perfo）。 Pro和Perfo将从公共可用的健康计量（www.healthmeasures.net）评估中得出并根据需要进行扩展，包括患者报告的结果测量信息系统（Promis），NIH NIH工具箱，评估神经系统和行为功能（NIH工具箱）的评估（NIH工具箱），以及短体性能监控（SPPER Battery（SppB），Co-cpelders cos-cpel-cpel-valers co-validers co-valsivers co-valsiD co-valsivers acc-validiD。为了验证在身体功能障碍范围内使用的COA，我们提出了与肌肉减少症相关的6种常见疾病，在UG3期间考虑了5种罕见疾病。在这两种情况下（肌肉减少症和罕见疾病），我们旨在对PF损伤的全部范围从轻度到重度进行采样，并在PF损伤的不同方面进行样品，因为它们会影响不同的诊断组。 我们的目标是生产核心PF结果集，可以在PF严重性连续性中广泛应用，以用于肌肉减少症和罕见疾病。 在UG3计划阶段，我们将与广泛的利益相关者，专家和FDA合作，以识别慢性，有症状并对PF产生影响的目标疾病领域。在此阶段的具体目的包括（1）召集利益相关者，包括患者，护理伙伴，临床医生，测量专家，付款人，监管机构和制药行业代表，围绕与新药批准有关的PF主题； （2）提出测试PF测量的模型条件（例如稀有疾病，肌肉减少症），并在我们提出的PF测量中确定潜在的差距； （3）提出精炼和测试的计划。 在UH3实施阶段，我们将确定现有，修订和新开发的评估工具，以评估为COA。可以从Promis和NIH工具箱中汲取大量COA核心构建块。这些PF措施适用于具有多种慢性病的儿童和成人，因此非常适合推导该机构寻求开发的横切COA核心集。然后，我们将根据FDA建议进行验证所需的研究。在此阶段的具体目的包括（1）生产PF Pro，源自混合方法研究和Promis PF Bank V2.0，包括轻度，中度和严重损坏的PF的简短形式以及全范围的PF； （2）产生源自NIH工具箱和SPPB的PF性能结果（perfo），以对影响PF的条件进行了优化； （3）在三个纵向研究中验证PF Pro和Perfo：一种解决了轻度 /中度PF损伤，一种解决中度 /重度PF损伤的问题，另一种解决了全方位的PF损伤。这将产生公共可用且可访问的核心临床结果集，用于测量药物临床试验中的身体功能，并有可能在各种条件下广泛概括。