Head-to-head comparison demonstrates strong agreement between the harmonized and the self-explanatory versions of the ALS functional rating scale: results of a prospective study

Introduction/Aims: The ALS Functional Rating Scale-Revised (ALSFRS-R) in its harmonized version is an established outcome parameter in amyotrophic lateral sclerosis (ALS). Assessment of the ALSFRS-R needs standard operating procedures (SOP) for procedural consistency. In contrast, the assessment of the self-explanatory (SE) version of the ALSFRS-R does not include SOPs. In this study, a head-to-head comparison of the harmonized and self-explanatory ALSFRS-R was performed. Methods: In a prospective study, the harmonized ALSFRS-R was assessed in 107 ALS patients, administered by a SOP-trained nurse. In parallel, all patients independently completed the ALSFRS-R-SE, either on a printed form (n = 36) or remotely via the ALS App (n = 71). Agreement between methods was investigated using Spearman's correlation, Lin's concordance correlation coefficient (CCC), Deming regression, Bland-Altman plots, and item-level statistics including Kendall's tau-b and the Stuart-Maxwell test. Results: Total scores from ALSFRS-R and ALSFRS-R-SE showed high correlation and concordance (CCC > 0.9). Deming regression and Bland-Altman analysis revealed no systematic bias. Item-level agreement was generally high, with limited variability in specific items such as handwriting, walking, and dyspnea. ALS progression rates were highly consistent. ALSFRS-R-SE remained robust across remote digital and paper-based assessments. Discussion: The strong agreement observed between the harmonized and self-explanatory versions of the ALSFRS-R supports the interchangeable use of the ALSFRS-R-SE. The self-explanatory format may facilitate remote digital assessment and reduce the complexity of ALSFRS-R assessment in both research and clinical practice. Further studies are warranted to validate the ALSFRS-R-SE across larger cohorts, multiple languages, and diverse rater groups.