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Introduction: Fatigue is highly prevalent and burdensome in systemic lupus erythematosus (SLE). The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) is a patient-reported questionnaire that measures physical and mental fatigue and consequent impact on daily living. Qualitative evidence of content validity in SLE is limited. This study (GSK Study 209226) assessed the content validity of the FACIT-Fatigue for SLE and explored patients' experiences of SLE-related fatigue using qualitative methods. Methods: Fatigue-related themes were identified through semi-structured, hybrid cognitive debriefing and concept elicitation interviews and evaluated for concordance with the FACIT-Fatigue. Results: Fatigue was experienced regularly by all participants (N = 15, 86.7% female) and was rated as the most bothersome symptom of SLE by 11/15 participants. All participants reported emotional impacts of fatigue, while 14/15 and 9/15 participants also reported impacts on social life and physical functioning, respectively. Most (12/15) reported that fatigue interfered with their ability to fulfill work-or school-related roles, and activities of daily living were limited in all participants. All (14/14) reported that a meaningful change in their level of fatigue would be the ability to have a more active and normal lifestyle. Concept mapping showed that all 13 FACIT-Fatigue items mapped directly onto concepts spontaneously mentioned by participants. Cognitive debriefing revealed that 13/15 participants found the instructions easy to understand and 11/15 participants endorsed the recall period (7 days) as appropriate. Participants found the FACIT-Fatigue items were clear and relevant. Most participants (11/ 15) reported that all response options adequately captured their experience of fatigue. Conclusions: Qualitative evaluation of the content validity of the FACIT-Fatigue supports it as an appropriate measure for assessing the impact of fatigue on daily living of patients with SLE. The tool is easily understood by patients and a valuable resource for measuring a common and debilitating symptom of this condition.

Background Fatigue is a key symptom in patients with systemic lupus erythematosus (SLE), and regulatory bodies recommend its assessment in clinical trials of SLE therapies. Methods This post hoc pooled analysis of the three BeLimumab In Subjects with Systemic lupus erythematosus (BLISS) Phase 3 randomised, double-blind, parallel-group controlled trials evaluated the measurement properties of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Patients (N = 2520) completed the FACIT-Fatigue every 4 weeks from baseline until the end of each study period. Internal consistency, test–retest reliability, convergent validity, and ability to detect changes in SLE were evaluated for the FACIT-Fatigue. Results The FACIT-Fatigue showed good internal consistency reliability (Cronbach’s alpha > 0.90), very good test–retest reliability (0.76 ≤ intraclass correlation coefficient ≤ 0.92), and moderate-strong convergent validity (0.49 ≤ |r| ≤ 0.86) against scale and summary measure scores from the Short Form 36 Health Survey Version 2. Correlations between FACIT-Fatigue and British Isles Lupus Assessment Group (BILAG) General/Musculoskeletal scores (0.24 ≤ |r| ≤ 0.43) supported convergent validity. Correlations between FACIT-Fatigue and the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores and SLE annualised flare rate were weak but in the expected direction (ranging from − 0.02 to − 0.25). Known-groups validity testing showed that the FACIT-Fatigue can significantly discriminate between patient groups with differing scores for SELENA-SLEDAI, BILAG (General and Musculoskeletal) ratings, and Physician’s Global Assessment (PGA). Patients showing improvement in PGA and meeting the BILAG responder criteria had significantly higher mean improvement in FACIT-Fatigue scores than those without improvements in either measure (Week 52 mean score difference [95% confidence interval]: − 4.0 [− 5.0, − 3.0] and −2.2 [−3.1, −1.2], respectively; both p < 0.0001). The range of important (i.e. meaningful) change in FACIT-Fatigue, based on multiple anchors, was 3–6 points. Conclusions The FACIT-Fatigue demonstrated adequate psychometric properties in patients with SLE. The body of evidence from the three BLISS trials (both pooled and individually) supports the FACIT-Fatigue as a reliable and valid measure of SLE-related fatigue in clinical trials. Clinical trial identifiers BLISS-SC (NCT01484496), BLISS-52 (NCT00424476), and BLISS-76 (NCT00410384).