New questionnaire assessing fatigue ‘reliable and valid’ for adults with PNH
Study finds FACIT-Fatigue accurately tracks symptoms, improvements
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A new 13-item questionnaire designed to assess fatigue and its impact on daily functioning in individuals with chronic illnesses appears to be accurate and may be appropriate for use in adults with paroxysmal nocturnal hemoglobinuria (PNH).
That’s according to a new analysis evaluating the validated tool, dubbed the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire, or FACIT-Fatigue.
The tool’s performance was tested in measuring fatigue among 135 adults with PNH who participated in two global Phase 3 clinical trials: APPLY-PNH (NCT04558918) and APPOINT-PNH (NCT04820530). Both trials assessed the effectiveness and safety of Fabhalta (iptacopan), an approved oral therapy for people with PNH, a disease characterized by red blood cell destruction that includes severe fatigue among its hallmark symptoms.
The study found that the FACIT-Fatigue questionnaire consistently measured fatigue severity and aligned closely with other patient-reported fatigue assessments. It also distinguished between mild and severe symptoms, the data showed, and detected improvement over time during treatment.
“The psychometric results reported here provide evidence suggesting that the scores produced by the FACIT-Fatigue are reliable and valid, and thus may be considered fit for purpose in measuring fatigue among adults with PNH,” the researchers wrote.
Still, the team noted, “further analyses using data from other PNH clinical trials,” particularly those with larger and more geographically diverse populations, are needed to confirm the generalizability of the findings.
The study, “Psychometric performance of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire among adults with paroxysmal nocturnal hemoglobinuria,” was published in the Journal of Patient-Reported Outcomes. It was sponsored by Novartis, the company that developed and markets Fabhalta.
In PNH, a rare blood disorder, overactivation of the complement system — part of the immune system — destroys red blood cells in a process called hemolysis. This can lead to low levels of healthy red blood cells, known as anemia, and PNH symptoms such as shortness of breath, weakness, and severe fatigue.
Researchers: Fatigue is a tough symptom to assess
Because fatigue can only be assessed through patients’ own descriptions of their experiences, patient-reported outcome measures are considered the gold standard for evaluating this symptom.
One widely used tool is the FACIT-Fatigue questionnaire. It evaluates tiredness, energy levels, and the impact of fatigue on daily activities over the previous seven days through 13 questions. Responses use a five-point verbal rating scale ranging from “Not at all” to “Very much.” Scores range from 0 to 52, with higher scores indicating less fatigue. The tool is listed in the U.S. Food and Drug Administration’s Clinical Outcome Assessment Compendium as an accepted measure of fatigue in PNH.
However, “at present there is little available evidence to demonstrate the reliability and validity of scores produced by the FACIT-Fatigue when measuring the fatigue experience of individuals with PNH,” the researchers wrote.
To determine whether the questionnaire consistently and accurately measured fatigue over time — and whether it was sensitive to changes during treatment — a team of international researchers analyzed data from the completed APPLY-PNH and APPOINT-PNH trials.
The analysis involved 95 participants from APPLY-PNH, who had a mean age of 51.4. Slightly more than two-thirds of the patients were men. It also covered 40 participants from APPOINT-PNH, of whom slightly more than half were men. The participants in that study had a mean age of 42.1
The individuals taking part in APPLY-PNH were primarily from Germany (21%), Italy (18%), and France (16%). Meanwhile, the APPOINT-PNH participants were mainly from China (50%), followed by France, Germany, and the U.K. (each 10%).
In both trials, participants completed the FACIT-Fatigue questionnaire (version 4) at the start of treatment, or baseline, and at follow-up visits on days 42, 126, 140, and 168.
FACIT-Fatigue questionnaire consistent, but also tracks changes
Across study visits in both trials, participants used the full range of response options, the data showed. Scores increased over time, indicating reductions in fatigue severity, consistent with clinical improvement during treatment.
The questionnaire demonstrated very high internal consistency at baseline and across follow-up visits in both trials, meaning the 13 questions worked closely together to measure fatigue. The tool also showed good to excellent test-retest reliability, with stable scores among patients whose condition did not change.
To assess validity, the researchers compared FACIT-Fatigue scores with other patient-reported fatigue measures. Scores were strongly associated with other fatigue assessments and clearly differentiated between patients with mild, moderate, and severe symptoms, the analysis showed.
Changes in scores were also closely aligned with changes in other fatigue measures, indicating that the tool was sensitive to improvement over time.
FACIT-Fatigue is a fit for purpose tool in measuring the fatigue experience of individuals with PNH.
When data from both trials were combined, additional analyses supported using the 13 responses as a single overall measure of fatigue, according to the researchers.
Finally, using data from the APPLY-PNH study, the scientists estimated the level of improvement on measures of fatigue that would be meaningful to patients. A one-level improvement in self-reported fatigue severity corresponded to a median increase of 7.5 to 9.5 points on the FACIT-Fatigue scale, suggesting that changes within this range represent meaningful improvement.
“FACIT-Fatigue is a fit for purpose tool in measuring the fatigue experience of individuals with PNH,” the researchers wrote. “Findings from the present analysis demonstrate that scores from the FACIT-Fatigue are reliable and valid in PNH, and add further empirical evidence supporting the use of the FACIT-Fatigue in PNH adult patient populations.”
