Qualitative study of fatigue in adults with primary mitochondrial disease: Development of the PROMIS Fatigue Mitochondrial Disease Short Form

Abstract

Background

Fatigue is a debilitating symptom in patients with primary mitochondrial disease nPMD). Developing new treatments that improve fatigue is a patient priority but is hampered by a lack of fit-for-purpose patient-reported outcome measures (PROMs). We aimed to understand the impact of fatigue on the lives of people with PMD and develop a brief PMD-specific PROM to evaluate fatigue in clinical trials.

Methods

Adults with genetically confirmed PMD and self-reported moderate-to-severe fatigue and myopathy/exercise intolerance participated in a concept elicitation interview to explore their experiences of fatigue. Interview transcripts were coded thematically using MAXQDA™. Characteristics and impacts that emerged from the interviews were mapped to items in the PROMIS® Fatigue item bank. Participants then engaged in a cognitive interview to assess relevance and understandability of PROMIS Fatigue items considered for the PROM.

Results

Twelve adults with PMD (n = 8 women, age 20–75 years) were interviewed. The most frequently reported characteristics of fatigue included tiredness, muscle weakness/fatigue, exhaustion, lack of energy, and mental fatigue. Fatigue affected patients' ability to perform daily life activities, including household chores, leisure activities, physical activity/exercise, and work/school, and negatively affected mood and relationships. Nine items were included in the final PROM based on level of endorsement of underlying concepts elicited by the concept elicitation interviews and relevance, clarity, and ease of answering, as assessed in the cognitive interviews.

Conclusion

The nine-item PROMIS Fatigue Mitochondrial Disease Short Form is the first PROM designed specifically to assess fatigue in PMD. This study demonstrates the content validity of the short form, and future longitudinal studies will assess its psychometric properties.