Content Validity and Psychometric Evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) in Patients with Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Patients with Crohn's disease (CD) or ulcerative colitis (UC) frequently experience fatigue, although it is often overlooked in medical research and practice. AIMS: To explore patients' experience of fatigue and evaluate content validity, psychometric properties, and score interpretability of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) in patients with CD or UC. METHODS: Concept elicitation and cognitive interviews were conducted with participants aged ≥ 15 years with moderately-to-severely active CD (N = 30) or UC (N = 33). To evaluate psychometric properties (reliability and construct validity) and interpretation of FACIT-Fatigue scores, data from two clinical trials were analyzed [ADVANCE (CD): N = 850; U-ACHIEVE (UC): 248]. Meaningful within-person change was estimated using anchor-based methods. RESULTS: Almost all interview participants reported experiencing fatigue. Over 30 unique fatigue-related impacts were reported per condition. The FACIT-Fatigue was interpretable for most patients. FACIT-Fatigue items had good internal consistency (Cronbach's α 0.86-0.88 for CD and 0.94-0.96 for UC); the total score displayed acceptable test-retest reliability (intraclass correlation coefficients > 0.60 for CD and > 0.90 for UC). FACIT-Fatigue scores had acceptable convergent validity with similar measures. A 7-10 point improvement for CD and 4-9 point improvement for UC on the FACIT-Fatigue total score may represent meaningful improvements. CONCLUSIONS: These results highlight the importance of fatigue among adolescents and adults with CD or UC and provide evidence that the FACIT-Fatigue is content valid and produces reliable, valid, and interpretable scores in these populations. Care should be taken if using the questionnaire with adolescents who may be less familiar with the word "fatigue." Clinical trial registration numbers NCT03105128 (date of registration: 4 April 2017) and NCT02819635 (date of registration: 28 June 2016).

Psychometric performance of the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) in a randomized, double-blind, placebo-controlled crossover study in subjects with mitochondrial disease.

BACKGROUND: The Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) is a 10-item patient-reported outcome (PRO) measure designed to assess the severity of mitochondrial disease symptoms. Analyses of data from a clinical trial with PMM patients were conducted to evaluate the psychometric properties of the PMMSA and to provide score interpretation guidelines for the measure. METHODS: The PMMSA was completed as a daily diary for approximately 14 weeks by individuals in a Phase 2 randomized, placebo-controlled crossover trial evaluating the safety, tolerability, and efficacy of subcutaneous injections of elamipretide in patents with mitochondrial disease. In addition to the PMMSA, performance-based assessments, clinician ratings, and other PRO measures were also completed. Descriptive statistics, psychometric analyses, and score interpretation guidelines were evaluated for the PMMSA. RESULTS: Participants (N = 30) had a mean age of 45.3 years, with the majority of the sample being female (n = 25, 83.3%) and non-Hispanic white (n = 29, 96.6%). The 10 PMMSA items assessing a diverse symptomology were not found to form a single underlying construct. However, four items assessing tiredness and muscle weakness were grouped into a "general fatigue" domain score. The PMMSA Fatigue 4 summary score (4FS) demonstrated stable test-retest scores, internal consistency, correlations with the scores produced by reference measures, and the ability to differentiate between different global health levels. Changes on the PMMSA 4FS were also related to change scores produced by the reference measures. PMMSA severity scores were higher for the symptom rated as "most bothersome" by each subject relative to the remaining nine PMMSA items (most bothersome symptom mean = 2.88 vs. 2.18 for other items). Distribution- and anchor-based evaluations suggested that reduction in weekly scores between 0.79 and 2.14 (scale range: 4-16) may represent a meaningful change on the PMMSA 4FS and reduction in weekly scores between 0.03 and 0.61 may represent a responder for each of the remaining six non-fatigue items, scored independently. CONCLUSIONS: Upon evaluation of its psychometric properties, the PMMSA, specifically the 4FS domain, demonstrated strong reliability and construct-related validity. The PMMSA can be used to evaluate treatment benefit in clinical trials with individuals with PMM. Trial registration ClinicalTrials.gov identifier, NCT02805790; registered June 20, 2016; https://clinicaltrials.gov/ct2/show/NCT02805790 .

Development and content validity of the Barth Syndrome Symptom Assessment (BTHS-SA) for adolescents and adults.

BACKGROUND: Barth Syndrome (BTHS) is a rare genetic disorder that presents as a complex of debilitating symptoms and reduced life expectancy. Well-developed, BTHS-specific assessments measuring primary signs and symptoms of BTHS are not currently available, making it difficult to evaluate treatment effects in BTHS clinical studies. The objective of this research was to develop symptom-focused patient-reported outcome (PRO) measures for use in clinical studies with adolescents and adults with BTHS. METHODS: Concept elicitation interviews (CEIs) with pediatric (n = 18, age < 16 years) and adult (n = 15, age ≥ 16 years) individuals with BTHS and/or their caregivers were conducted to identify signs and symptoms relevant to BTHS and important to individuals with the condition. Based on CEI results, questionnaire construction activities were conducted to create unique adolescent and adult versions of the Barth Syndrome-Symptom Assessment (BTHS-SA). The questionnaires were evaluated in cognitive debriefing interviews (CDIs) with adolescents (n = 12; age 12- < 16 years) and adults (n = 12; age ≥ 16 years) with BTHS to assess relevance and readability of the tools. RESULTS: During the CEIs, a total of 48 and 40 signs and symptoms were reported by the pediatric and adult groups, respectively; 31 were reported by both age groups. Fatigue/tiredness and muscle weakness were the symptoms most frequently reported by both pediatric and adult patients with BTHS as important to improve with an effective treatment. The CEI results informed construction of a nine-item version of the BTHS-SA for adolescents and an eight-item version for adults. Developed for daily administration, each version asks respondents to rate symptom severity "at its worst" over the 24 h prior to administration. CDIs with both adolescents and adults with BTHS demonstrated that each BTHS-SA version was reflective of the disease experience and that respondents could interpret the questionnaire as intended and provide responses that accurately reflected their symptom experience. CONCLUSIONS: The BTHS-SA adolescent and adult versions are content-valid PRO measures that can be used to evaluate severity of disease-specific symptoms in future clinical trials. Given the lack of available and well-developed assessments in this underserved therapeutic area, these tools fulfill a need for clinical researchers developing treatments for individuals with BTHS.

Development of a Patient-Reported Outcome Questionnaire to Evaluate Primary Mitochondrial Myopathy Symptoms: The Primary Mitochondrial Myopathy Symptom Assessment.

OBJECTIVES: Primary mitochondrial myopathy (PMM) is a genetic condition characterized by life-limiting symptoms such as muscle weakness, fatigue, and pain. Because these symptoms are best reported by individuals with PMM, the objective of this qualitative research study was to develop a PMM-specific patient-reported outcome (PRO) questionnaire. METHOD: Individuals with PMM were interviewed, identifying the most salient symptoms of PMM and assessing the resulting questionnaire's relevance and comprehensibility. RESULTS: Developed based on patient interviews, the 10-item Primary Mitochondrial Myopathy Symptom Assessment assesses patients' symptom experiences at their worst in the last 24 hours. Individuals with PMM confirmed the concepts of the questionnaire as relevant and comprehensive to their symptom experiences and responded to the items consistently with developers' intentions. CONCLUSIONS: The Primary Mitochondrial Myopathy Symptom Assessment is a content-valid PRO questionnaire with qualitative and quantitative support as a valuable tool to evaluate and monitor the day-to-day experience of PMM symptoms from the patient perspective.

Understanding the life experience of Barth syndrome from the perspective of adults: a qualitative one-on-one interview study.

BACKGROUND: Barth syndrome (BTHS, OMIM 302060) is a rare, life-threatening, x-linked genetic disorder that occurs almost exclusively in males and is characterized by cardiomyopathy, neutropenia, skeletal muscle myopathy primarily affecting larger muscles, and shorter stature in youth. A greater number of individuals with BTHS are now surviving into adulthood due to advancements in diagnosis and disease management. Given these improvements in life expectancy, understanding the disease experience over time has become increasingly important to individuals with the condition, treatment developers, and regulatory agencies. A study was conducted to explore the experience of BTHS from the perspective of adult males at least 35 years of age with the condition via in-depth qualitative interviews. RESULTS: Findings showed that adults with BTHS experienced a variety of signs/symptoms with variable onset and severity throughout their lives, the most frequently reported being the symptoms of tiredness, muscle weakness, and a fast and/or irregular heart rate, and the sign of short stature in youth. These signs/symptoms negatively impacted individuals' emotional, physical, social, and role functioning. Tiredness and weakness impacted some individuals' physical functioning from an early age and into adulthood. These symptoms generally worsened over time, increasingly interfering with individuals' ability to fully participate in paid and unpaid labor and to partake in family and leisure activities. CONCLUSIONS: This research complements recent studies characterizing the potentially degenerative and progressive nature of BTHS and can encourage future research into the natural history and progression of BTHS in untreated individuals. Participants' interview responses revealed a range of symptoms and the potential for multiple impacts on individuals' physical, social, emotional, and role functioning as a result of BTHS symptoms, yet also revealed variability in severity of experience as well as the possibility of resilience and adaptation to the condition.