Assessment of the MFSAF v4.0 and PROMIS Fatigue 7a to Measure Outcomes in Myelofibrosis: Validation from a Non-interventional Mixed Methods Study.
Key claim: MFSAF v4.0 and PROMIS Fatigue 7a are content-valid, reliable, and construct-valid patient-reported measures in primary and secondary myelofibrosis, with patients judging a 1-to-2-point item change as meaningful, supporting their use as clinical trial endpoints.
Abstract
INTRODUCTION: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.
Why this matters
MPN symptom research depends on trustworthy patient-reported instruments, and until now MFSAF v4.0 and PROMIS Fatigue 7a were used in MF trials without formal MF-specific content-validity and psychometric grounding. This study anchors both tools in patient experience and defines a 1-to-2-point item-level meaningful change, which will shape how fatigue, splenomegaly-related symptoms, night sweats, pruritus, bone pain, and constitutional fever are quantified and interpreted across future MF trials and real-world symptom studies.