A qualitative study assessing content validity of Neuro-QoL fatigue and PROMIS mental fatigue in m.3243A>G primary mitochondrial disease

Background Fatigue is frequently reported and clinically significant in m.3243A > G primary mitochondrial disease (PMD) patients, hereafter PMD. This study aimed to understand the lived experience of PMD from the patient’s perspective with a particular focus on fatigue, and to explore the content validity of an existing measure of fatigue, the Neuro-QoL short form version 1 – Fatigue (Neuro-QoL SFv1-F). Methods Genetically confirmed PMD patients were recruited from the USA and the Netherlands. Eighteen participants took part in concept elicitation (CE) interviews. Seventeen participants, three of whom had not taken part in the CE interviews, took part in cognitive debrief (CD) interviews. Some participants took part in both interviews, whilst others participated in only a CE or CD interview. CE interviews explored participants’ lived experience of symptoms and impacts, with a focus on fatigue, while CD interviews explored participants’ understanding of the measures. Interview transcripts were analyzed using thematic analysis. Following CE interviews, characteristics of fatigue were mapped to the Neuro-QoL SFv1-F items to assess whether the measure comprehensively captured the lived experience of PMD-related fatigue. Results This study included 21 adult PMD participants (age 46.3 ± 9.3 years, 81% female, and 52.4% had moderate clinician-reported disease severity). CE interviews identified 21 signs and symptoms of PMD, with physical and mental fatigue, hearing loss, and pain most frequently reported and described as bothersome. Impacts included reduced physical functioning, emotional impacts, affected social life, and work or school impacts, with a reliance on assistance from others. Item mapping showed that the Neuro-QoL SFv1-F captured core physical fatigue concepts but did not adequately capture mental fatigue. To address this gap, a new measure, the PROMIS Mental Fatigue Mitochondrial Disease Short Form (PROMIS MF-MD SF), was developed. Cognitive debriefing of the Neuro-QoL SFv1-F and the PROMIS MF-MD SF confirmed that the measures were understandable and relevant to patients with suitable response options. Participants discussed that they felt a 1-category improvement or worsening on any item of the Neuro-QoL SFv1-F and PROMIS MF-MD SF meaningful. Conclusions This study provides support for the content validity and suitability of the Neuro-QoL SFv1-F and PROMIS MF-MD SF in adults with PMD. Clinical trial number Not applicable.