Northwestern University Clinical Outcome Assessment Team (NUCOAT)

我们建议开发和验证公开可用的身体功能（PF）临床结局评估（COA），因为它们与一系列慢性疾病相关，适合监管目的。这些COA将评估PF作为患者报告结局（PRO）和性能结局（PerfO）。PRO和PerfO将来源于公开的HealthMeasures（www.healthmeasures.net）评估，并在必要时进行扩展，包括患者报告结局测量信息系统（PROMIS）、神经和行为功能评估的NIH量表（NIH EQUIPMENT）和短体力活动组合（SPPB），并与身体活动的加速度计监测共同验证。为了验证COA在身体功能障碍范围内的使用，我们提出了6种与肌肉减少症相关的常见疾病和5种罕见疾病，供UG 3阶段考虑。在这两种情况下（肌肉减少症和罕见疾病），我们的目标是采样从轻度到重度的PF损伤的全方位，并采样PF损伤的不同方面，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UG 3规划阶段，我们将与广泛的利益相关者、专家和FDA合作，以确定慢性、症状性和对PF有影响的目标疾病领域。该阶段的具体目标包括：（1）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，围绕与新药批准相关的PF主题;（2）提出测试PF测量的模型条件（例如，罕见疾病，肌肉减少症），并确定我们提出的PF措施中的潜在差距;以及（3）提出改进和测试计划。 在UH 3实施阶段，我们将识别现有、经修订及新开发的评估工具，作为COA进行评估。可以从PROMIS和NIH数据库中提取大量COA核心构建模块。这些PF措施适用于患有各种慢性病的儿童和成人，因此是获得该机构寻求开发的跨领域COA核心集的理想选择。然后，我们将根据FDA的建议进行验证所需的研究。这一阶段的具体目标包括：（1）从混合方法研究和PROMIS PF银行v2.0中产生PF PRO，包括轻度、中度和严重受损PF的简短形式，以及全范围PF;（2）产生PF性能结果（PerfO），从NIH ESTA和SPPB中产生，针对影响PF的条件的反应性进行优化;（3）在三项纵向研究中对PF PRO和PerfO进行了验证：一项针对轻度/中度PF损害，一项针对中度/重度PF损害，一项针对全范围PF损害。这将产生公开可用和可访问的核心临床结果集，用于在药物临床试验中测量身体功能，具有跨条件广泛推广的潜力。

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.