Assessment of the MFSAF v4.0 and PROMIS Fatigue 7a to Measure Outcomes in Myelofibrosis: Validation from a Non-interventional Mixed Methods Study

Myelofibrosis (MF) is a bone marrow cancer causing impactful symptoms, notably excessive fatigue. While the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 and PROMIS Fatigue 7a are frequently used in clinical trials, they lack published evidence for content validity in MF. This study evaluated the content validity, psychometric properties, and patient-perceived meaningful change for both measures in an MF population. This observational, mixed-methods study involved qualitative concept elicitation (CE) and cognitive debriefing (CD) interviews (n = 17) with patients with primary or secondary MF. Psychometric properties, including test–retest reliability and construct validity, were assessed via online surveys administered at two timepoints (n = 39). Interviews confirmed fatigue as a universal symptom. CD results showed both instruments were well understood, relevant, and comprehensive, with no recommended changes. Participants identified a 1-to-2-point change on individual item ratings as a meaningful improvement. Psychometric analysis demonstrated excellent internal consistency (α > 0.80) and strong test–retest reliability (ICCs 0.85–0.93) for both measures. Construct validity was supported by expected large correlations with similar constructs (MSAS-SF) and lower correlations with distal concepts such as mental health (SF-12 v2). The MFSAF v4.0 and PROMIS Fatigue 7a effectively capture key MF symptoms and impacts. Both measures are well understood by patients and demonstrate sufficient reliability and validity for use as clinical trial endpoints. Patients can clearly conceptualize and describe meaningful changes in their symptom experience using these tools. This study evaluated how well two questionnaires, the MFSAF v4.0 and the PROMIS Fatigue 7a, measure symptoms and fatigue in people living with myelofibrosis. Myelofibrosis is a disease that often causes severe symptoms such as fatigue and weakness that can affect daily life and quality of life. The aim was to assess whether these patient-reported outcome measures accurately capture symptom and fatigue experiences reported by patients, and to explore what item-level changes patients considered meaningful. The study involved interviews with people with myelofibrosis, as well as surveys completed at two timepoints. Both the MFSAF v4.0 and the PROMIS Fatigue 7a showed evidence of reliability and consistency, were easy for patients to understand, and provided evidence of validity for measuring symptoms among patients with myelofibrosis. Patients generally felt that a change of 1 to 2 points on individual questionnaire items represented a meaningful improvement. Patients also reported that not all symptoms needed to improve for an overall change in their scores to feel meaningful. Overall, the results support considering the MFSAF v4.0 and the PROMIS Fatigue 7 questionnaires as outcome measures in myelofibrosis clinical trials. Further research is needed to confirm how well these measures detect change over time.