Understanding Holistic Patient-Relevant Measurement in Amyotrophic Lateral Sclerosis: A Mixed-Methods Content Validity and Exploratory Rasch Analysis of Selected Clinical Outcome Assessments

Living with amyotrophic lateral sclerosis (ALS) has a profound impact on function and health-related quality of life (HRQoL). This mixed-methods study aimed to cognitively debrief selected ALS outcome measures to investigate their relevance and conduct exploratory Rasch Measurement Theory (RMT) analyses to assess targeting. Semi-structured interviews were conducted (January–September 2024) with people living with ALS (PLwALS) and clinicians to cognitively debrief selected patient- and clinician-reported outcome (PRO and ClinRO) measures. The PRO measures debriefed with PLwALS were Rasch Overall ALS Disability Scale (ROADS), 5-item ALS Assessment Questionnaire (ALSAQ-5), and Neurological Fatigue Index for Motor Neurone Disease (NFI-MND). ROADS and ClinRO ALS Functional Rating Scale-Revised (ALSFRS-R) were debriefed with clinicians. Interview transcripts were qualitatively analyzed; structured codes were used to compile data on item relevance and comprehensiveness. Exploratory RMT analysis was conducted using quantitative data from PLwALS responses to evaluate selected PRO psychometric properties. Qualitative analysis of interviews with 31 PLwALS found that PROs were meaningful and relevant, and identified the relevance of individual items. Clinicians ( n = 10) endorsed ALSFRS-R as a relevant and meaningful measure, and supported ROADS’ conceptual coverage and response category. RMT analysis indicated evidence of good targeting, reliability, and item fit for the PROs, with some exceptions for ALSAQ-5. This study supports the use of ALSFRS-R, ROADS, ALSAQ-5, and NFI-MND to measure meaningful aspects of ALS, with support for ALSAQ-5 qualified by its limited measurement precision. Scores from these measures can provide important insights into the lived experience of PLwALS, characterizing disease progression and HRQoL.