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作为患者报告的结果（PRO）和性能结果（PerfO）。PRO和PerfO将从公开可用的HealthMeasures （www.healthmeasures.net）评估中衍生，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）和短物理性能电池（SPPB），与加速度计监测身体活动共同验证。为了验证coa在各种身体功能障碍中的应用，我们提出了UG3阶段与肌肉减少症相关的6种常见疾病和5种罕见疾病。在这两种情况下（肌肉减少症和罕见疾病），我们的目标是对从轻度到重度的全范围PF损伤进行采样，并对影响不同诊断组的PF损伤的不同方面进行采样。我们的目标是产生核心PF结果集，可以广泛应用于PF严重程度连续体，用于肌肉减少症和罕见疾病的调节使用。

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.