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ORIGINAL RESEARCH article

Front. Hematol.
Sec. Red Cells, Iron and Erythropoiesis
Volume 4 - 2025 | doi: 10.3389/frhem.2025.1490130
This article is part of the Research Topic Unraveling Mechanisms and Implications of Anti-RBC Antibodies in Transfusion Medicine View all 6 articles

FACIT-Fatigue Scale in Patients with Cold Agglutinin Disease: Psychometric Validation and Estimation of Clinically Meaningful Change

Provisionally accepted
David Cella David Cella 1*Quentin A Hill Quentin A Hill 2Alia Karaouni Alia Karaouni 3Florence Joly Florence Joly 4Timothee Sourdille Timothee Sourdille 5Frank Shafer Frank Shafer 5Marek Wardęcki Marek Wardęcki 6Mark Kosinski Mark Kosinski 7Alexander Röth Alexander Röth 8
  • 1 Department of Medical Social Sciences, Feinberg School of Medicine,, Northwestern University, Evanston, United States
  • 2 Department of Clinical Hematology,, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
  • 3 BMAPS SARL, Geneva, Switzerland
  • 4 Sanofi, Chilly-Mazarin, France
  • 5 Sanofi, Bridgewater, United States
  • 6 Sanofi, Warsaw, Masovian, Poland
  • 7 QualityMetric, Johnston, RI, United States
  • 8 Department of Hematology and Stem Cell Transplantation, West German Cancer Center, Essen University Hospital, Essen, North Rhine-Westphalia, Germany

The final, formatted version of the article will be published soon.

    Purpose: To validate the use of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire in cold agglutinin disease (CAD) patients using qualitative and quantitative methods and to estimate Meaningful Within Patient Change (MWPC).Methods: Qualitative assessment used outcomes from a survey among CAD patients and their caregivers in US.Quantitative assessment used outcomes from two Phase-3 trials in CAD wherein fatigue was evaluated as a key secondary endpoint using the FACIT-Fatigue questionnaire.The reliability, validity, and responsiveness of the FACIT-Fatigue questionnaire were assessed. MWPC was estimated using anchor-based (mean change, receiver operating characteristic [ROC] curves, and logistic regression) and distribution-based methods.Results: Qualitative analyses (n=16) showed that fatigue was the most common and bothersome symptom. All patients reported that FACIT-Fatigue questionnaire captured their experiences of CAD-related fatigue.Quantitative analysis included 55 patients from both studies. Items of FACIT-Fatigue scale were internally consistent (Cronbach's alpha coefficient: 0.94 at baseline; 0.96 at Week 26). Generally, correlations showed good convergent validity (>0.40). The MWPC estimates ranged from 2.0 to 15.7. Based on more robust ROC and regression-based methods, IQR of MWPC estimates was 4.1-7.3, and individual responder definitions were in range of 5-8 points, where "5" is the lowest recommended MWPC threshold for FACIT-Fatigue in CAD.FACIT-Fatigue is a reliable, valid, responsive scale in CAD. The MWPC estimates for FACIT-Fatigue in patients with CAD were consistent with other disease estimates published previously, and "5" can be considered as the lowest recommended threshold for meaningful clinical response in patients with CAD.

    Keywords: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Cold agglutinin disease (CAD), Meaningful Within Patient Change (MWPC), FACIT-Fatigue questionnaire, Psychometric validation

    Received: 02 Sep 2024; Accepted: 04 Feb 2025.

    Copyright: © 2025 Cella, Hill, Karaouni, Joly, Sourdille, Shafer, Wardęcki, Kosinski and Röth. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: David Cella, Department of Medical Social Sciences, Feinberg School of Medicine,, Northwestern University, Evanston, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.