FACIT-Fatigue questionnaire reliable CAD measure, study finds
Patient impressions, trial data confirm questionnaire's validity
The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, a widely used questionnaire to assess fatigue, is reliable, valid, and responsive to changes in the severity of cold agglutinin disease (CAD), according to a study.
The findings relied on CAD patients’ impressions of the FACIT-Fatigue scale and data from two Phase 3 clinical trials that evaluated changes FACIT-Fatigue scores as a key secondary goal. “These analyses confirm the validity of using the FACIT-Fatigue scale in CAD and provide a clinically meaningful threshold for future CAD studies,” the researchers wrote.
The study, “FACIT-Fatigue scale in patients with cold agglutinin disease: psychometric validation and estimation of clinically meaningful change,” was published in Frontiers in Hematology. It was funded by Sanofi, the developer of Enjaymo (sutimlimab-jome), the only CAD-approved therapy.
In CAD, self-reactive antibodies known as cold agglutinins bind to red blood cells at low temperatures, causing them to clump together and be marked for destruction. Low red blood cells, as well as their aggregation, can result in several CAD symptoms, including dizziness, headache, shortness of breath, muscle weakness, heart problems, and pain.
“Profound and chronic fatigue is one of the most common symptoms of CAD and severely affects patients’ quality of life,” the researchers wrote.
Measuring the most common, most bothersome CAD symptom
In a 2022 internet-based survey, 90% of CAD patients in the U.S. said they experienced fatigue, with nearly half experiencing it every day. Overall, fatigue hampered patients’ ability to complete daily tasks.
The FACIT-Fatigue assessment is a widely used, self-reported, 13-item questionnaire designed to examine fatigue and its impact on a person’s daily activities and functioning over the most recent seven days. Scoring ranges from 0 to 52, with higher scores indicating less fatigue.
A team of researchers in the U.S. and Europe, including some working at Sanofi, conducted a two-part study to validate the use of FACIT-Fatigue in people with CAD and estimate clinically meaningful score changes in this patient population.
In the first part, researchers asked 16 adults with CAD in the U.S. to complete a survey and the FACIT-Fatigue assessment. All participants were white, 62.5% were women, and 68.8% had received a CAD diagnosis within the last 1.5 years.
In line with previous findings, results showed that fatigue was “the most common and bothersome symptom associated with CAD … and had a significant impact on a patient’s ability to perform routine daily activities,” the team wrote.
All but one patient (93.8%) reported feeling fatigued due to CAD. Nearly all of these patients (80%) experienced fatigue daily, while the remaining 20% reported feeling fatigued a few days per week. Some 66.7% of these patients described their fatigue as physical, 13.3% as mental, and 20% as both physical and mental.
After completing FACIT-Fatigue, all participants said the questionnaire captured their experiences with CAD-related fatigue, measured important concepts of fatigue, and was not missing any essential elements. Two questionnaire items — “I feel fatigued” and “I have trouble starting things because I’m tired” — were most frequently selected as most important to patients.
Follow-up interviews with an additional 21 CAD patients confirmed that the FACIT-Fatigue items were easy to understand and relevant to their experience.
In the second part of the study, the team collected outcome data from 55 CAD patients who participated in one of the two Phase 3 trials that supported approvals of Enjaymo (now marketed by Recordati): CARDINAL (NCT03347396) and CADENZA (NCT03347422).
The trials’ primary goal was to assess changes in blood levels of hemoglobin, the protein that carries oxygen in red blood cells, a key measure of CAD severity. Secondary goals included changes in FACIT-Fatigue scores. All 55 patients had available FACIT-Fatigue data at study’s start and after 26 weeks (about six months) of treatment.
According to the analysis, measures of internal consistency, or how reliable the questionnaire was in measuring fatigue, far exceeded the minimum reliability threshold.
FACIT-Fatigue scores were also strongly associated with hemoglobin levels and scores of the physical and mental components of SF-12v2 — a short-form health survey of functioning and well-being — and Patient Global Impression of Severity (PGI-S).
The mean FACIT-Fatigue score was significantly higher, indicating less fatigue, in patients with normal or near-normal hemoglobin levels at week 26 than in those with lower levels.
Similarly, changes in FACIT-Fatigue scores over 26 weeks significantly correlated with changes in hemoglobin levels, SF-12v2’s physical and mental component scores, and PGI-S.
Increases in FACIT-Fatigue scores were also highest, indicating reduced fatigue, among patients who reported the greatest improvement in overall health, as indicated by the patient global impression of change assessment.
Finally, several statistical analyses pointed to a five-point change in FACIT-Fatigue score as the lowest clinically meaningful change threshold for this scale in people with CAD. These estimates “were consistent with those published previously,” the team wrote.
“Results from the analyses presented above show that FACIT-Fatigue is a reliable, valid, responsive [patient reported outcome] measure for patients with CAD,” the researchers concluded.
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