Abstract
BACKGROUND: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders that can negatively affect one's health-related quality of life (HRQoL) because of pain from phototoxic reactions and the avoidance of sun exposure that is recommended. There is a need for reliable and valid patient-reported outcome measures (PROMs) that address all aspects of EPP/XLP, including symptoms and impacts. Our objective was to assess 2 recently developed PROMs, the Sunlight Exposure Diary and the EPP Impact Questionnaire (EPIQ), to determine their factor structure and explore their psychometric properties. RESULTS: During a clinical trial conducted from January 2023 to August 2024 evaluating an oral therapy to improve sunlight tolerance in adults, participants with EPP or XLP completed the Sunlight Exposure Diary, the EPIQ, and other PROMs (PROMIS-57 v2.1, PROMIS Short Form v2.0 - Social Isolation, and PROMIS-Neuropathic Pain Quality v2.0 scales), at multiple time points via electronic data capture. Data from all treatment groups were combined for analysis. 65 participants with a baseline and at least 1 follow-up assessment on the EPIQ were included (mean age = 45, 51% male, whole-blood metal-free PPIX levels = 9335.5 µg/L). Exploratory Factor Analysis identified 1 underlying factor in the Sunlight Exposure Diary ("Tingling/Itching") and 3 in the EPIQ ("Duration of Full Reaction," "Overall Change," and "Overall Severity and Impact"). The factor from the Sunlight Exposure Diary showed less consistent performance. A single item from the Sunlight Exposure Diary was also evaluated (the Daily Daylight Tolerance Over 2-Week Interval). The 3 factors from the EPIQ demonstrated acceptable to strong psychometric properties in terms of reliability (internal consistency, test-retest), validity (construct, known groups), and responsiveness. Ranges for meaningful change, using anchor- and distribution-based approaches, were established. CONCLUSIONS: These PROMS address the need for EPP/XLP-specific measures that assess the duration, severity, and impact of early warning symptoms and full phototoxic reactions, and capture impacts of EPP and XLP on well-being and HRQoL. Results suggest that the PROMs are reliable and valid, supporting their use in future research and relevant for assessing the experiences of individuals with EPP or XLP.