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 conditions with mildly impaired PF, we propose irritable bowel syndrome (IBS) as a model. For conditions with moderately/severely-impaired PF, we propose sarcopenia as a model. Our goal is to produce core PF outcome sets that can be applied broadly for regulatory use. 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 physical function. 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., IBS, sarcopenia), and potential identify 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 three short forms for mildly-impaired, moderately/severely-impaired, 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 two longitudinal studies: one addressing mild physical function impairment (IBS), and one addressing moderate-to-severe PF impairment (sarcopenia). The end-result of this work will be the delivery of publicly-available and accessible core clinical outcome sets for measuring physical function in pharmaceutical clinical trials, with potential widespread generalizability across conditions.
|Effective start/end date||9/10/19 → 8/31/22|
- Food and Drug Administration (5UG3FD006794-02)
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