This research will define and validate guidelines for interpretation of commonly used patient-reported outcome measures (PROMs) for pain and physical function domains among patients with advanced knee osteoarthritis (OA) receiving medical, rehabilitation, or surgical treatment. The Framingham OA study found that 33% of men and 42% of women have radiographic changes consistent with knee OA. While x-ray changes do not correlate with symptom severity, validated patient-reported outcome measures (PROMs) can quantify knee OA pain severity, longitudinal symptom changes, and OA-associated functional limitations in groups of patients. Thus, professional societies endorse PROM use in knee OA and CMS will mandate PROM capture and reporting for all knee OA patients electing total knee replacement (TKR) by 2027. Today’s electronic health records can capture knee-OA PROMs for use in clinical care, yet sparse evidence exists to guide PROM interpretation in individual patients. This research will generate guidelines tailored to the common comorbidities of knee OA patients who are likely to be older, obese, and have multiple physical and emotional comorbidities that influence pain and physical function. Study feasibility and efficiency is supported by the use of two existing cohorts: (1) the NIAMS-funded Osteoarthritis Initiative cohort (n=4700) and (2) a 12-site cohort of patients evaluated for TKR (n=4000; PCORI). Both cohorts include identical OA-specific and universal PROMs captured at initial evaluation and 12 months with varied treatments; demographic and social factors; and medical, emotional, and musculoskeletal comorbidities. An interdisciplinary team of knee OA experts and stakeholders will review the clinical utility of statistical PROM interpretation guidelines to generate dissemination tools for use in clinical care. The Specific Aims include: Aim 1. Define PROM interpretation guidelines specific to patient attributes and comorbidities, as needed, for both knee OA pain and physical function domains to inform non- operative and TKR interpretation of symptom changes. Analyses will use existing data with the commonly used OA-specific (KOOS, WOMAC) and universal PROMs (SF36, VR12, PROMIS), and self-evaluated transitions (pre-to-one-year post TKR). Patients with key comorbidities (e.g., widespread pain, poor emotional health, cardiopulmonary conditions) and diverse attributes (sex, age, race and ethnicity) will be examined. Aim 2. Validate pain and physical function PROM interpretation guidelines in a prospective sample of knee OA patients (n=800) and assess PROMs bi-monthly for 12 months to define improvement trajectories. Aim 3. Evaluate use and adoption of knee OA PROM interpretation guidelines through the prospective sample of orthopedic clinicians and their patients to serve future implementation. As PROMs are adopted widely, these guidelines will support consistent PROM interpretation and will inform future knee OA clinical care and research.