Abstract
BACKGROUND: People with hemophilia (PWH) experience frequent joint bleeding, resulting in pain and functional impairment. Generic and disease-specific patient-reported outcome (PRO) instruments have been used in clinical studies, but rarely in the comprehensive hemophilia care setting. OBJECTIVE: The objective of this study was to assess construct validity of PRO instruments measuring pain, functional impairment, and health-related quality of life in US PWH with a history of joint pain/bleeding. METHODS: Adult male PWH completed 4 PRO instruments (EQ-5D-5L with visual analog scale, Brief Pain Inventory v2 Short Form [BPI], SF-36v2, Hemophilia Activities List [HAL]) and underwent a musculoskeletal examination (Hemophilia Joint Health Score v2.1 [HJHS]). Construct validity between index and domain scores was evaluated by Pearson product-moment correlation coefficient. RESULTS: A total of 381 PWH were enrolled. EQ-5D-5L Mobility correlated with BPI, SF-36v2, and HAL domains related to pain, physical function, and activity of the lower extremities. EQ-5D-5L Self-Care correlated only with HAL Self-Care. EQ-5D-5L Usual Activities correlated with BPI Pain Interference and domains within SF-36v2 and HAL related to pain and physical function/activities (particularly those involving the lower extremities). EQ-5D-5L Pain/Discomfort correlated with Bodily Pain and Physical Summary on SF-36v2, HAL Overall Activity, and all BPI pain domains. EQ-5D-5L Anxiety/Depression correlated with social/emotional/mental aspects of SF-36v2. On BPI, most pain domains correlated with Bodily Pain and Physical Health Summary on SF-36v2 and Overall Activity on HAL. On SF-36v2, Physical Functioning, Role Physical, Bodily Pain, and Physical Health summary scores correlated with all the domains of HAL except Self-Care. For HJHS, Ankle and Total scores correlated with SF-36v2 Physical Functioning and HAL Lying/Sitting, Leg Function, Complex Lower Extremity Activity, and Overall Activity. CONCLUSION: All PRO instruments have high construct validity but provide different levels of detail in describing effects of hemophilia. Instrument choice may depend on individuals' symptoms, treatment planning goals, or outcome tracking research objectives, with consideration for administrative burden.