A Triangulation Approach to Develop a Conceptual Framework for the Patient-Reported Outcome Measures across the Life Cycle: A Case of Patients with X-Linked Hypophosphatemia

OBJECTIVES: This study aims to develop a comprehensive and clinically meaningful conceptual framework for patient-reported outcome measures (PROMs) in X-linked hypophosphatemia (XLH), a rare, progressive genetic disorder affecting the musculoskeletal system. It also seeks to incorporate lifecycle adaptations in the framework to reflect the disease's evolution.

METHODS: A triangulation methodology was employed, combining systematic-reviews of qualitative studies on XLH disease burden, in-depth interviews with XLH patients or caregivers, and a modified two-round Delphi survey. Framework analysis of interview data was conducted using MAXQDA Analytics Pro 2022 and Microsoft Excel, with a codebook derived from the systematic-reviews and relevant concepts. The final conceptual model, including its thematic structure and lifecycle adaptations, was refined and validated through the Delphi process, engaging experienced XLH clinicians to make a consensus on the clinical importance of patient-reported items of health-related quality of life.

RESULTS: We identified twenty-two themes and 127 subthemes from the Screening of six databases, which yielded six qualitative studies from an initial pool of 411, focusing on the burden of XLH and relevant concept sets. In-depth interviews with four adult patients and seven caregivers of children and adolescent patients revealed six main-themes for adults (symptoms/physical functioning/social functioning/treatment burden/emotional burden/family burden) and additional five main-themes for younger patients (development/peer abuse/caregiver's emotional burden/caregiver's conflict with family/caregiver's daily life impact). Delphi survey results derived the final conceptual framework of clinically meaningful XLH PROMs consisting of twenty-seven subthemes for adults and thirty-two subthemes. Significant differences in main-themes and subthemes were observed between adult and younger patients.

CONCLUSIONS: The study provides a deep insight into the construction of disease burden for XLH patients and highlights the importance of lifecycle considerations in assessing their quality of life. These findings have potential implications for other lifelong inherited diseases and chronic conditions, underscoring the need for tailored approaches in patient-centered healthcare assessment and management.