Development of the Lee Symptom Scale–Skin Sclerosis for chronic GVHD–associated sclerosis

Abstract Sclerosis is a highly morbid manifestation of chronic graft-versus-host disease (cGVHD), associated with distressing symptoms and significant long-term disability. A patient-reported outcome (PRO) measure for cGVHD-associated sclerosis is essential to advance therapeutic trials. We aimed to develop a PRO for adults with cGVHD-associated sclerosis and evaluate and refine its content validity. Adults aged ≥18 years with cGVHD-associated sclerosis participated in semistructured interviews to identify salient symptoms and functions. Sclerosis-relevant symptoms and functions from existing PROs were also used to prompt discussion of topics not spontaneously mentioned. Symptoms and functions (subcodes) of importance were clustered and mapped to overarching domains (codes) using inductive analysis, and candidate items were developed. Cognitive interviews were used to evaluate content validity of the items, response options, recall period, and respondent instructions. Thirty-six open-ended interviews, conducted to saturation, revealed the breadth of the patient experience with cGVHD-associated sclerosis including 5 overarching domains: (1) skin changes, (2) symptoms, (3) emotional and social functioning, (4) mobility restrictions, and (5) activity limitations. A pool of 54 items was tested and iteratively refined through cognitive debriefing interviews (n = 25). Phrasing changes were made to improve relevance and comprehension. One item was removed, and 2 items were added to address respondent feedback, resulting in 55 items. Results support the relevance, comprehensibility, and comprehensiveness of the provisional Lee Symptom Scale–Skin Sclerosis. Concept elicitation and cognitive interviewing have informed the development of the Lee Symptom Scale–Skin Sclerosis. Psychometric testing and determination of minimal clinically important differences are underway in an external cohort to validate the PROs.