Item response theory analysis of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised in the Pooled Resource Open-Access ALS Clinical Trials Database

Our objective was to examine dimensionality and item-level performance of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) across time using classical and modern test theory approaches. Confirmatory factor analysis (CFA) and Item Response Theory (IRT) analyses were conducted using data from patients with amyotrophic lateral sclerosis (ALS) Pooled Resources Open-Access ALS Clinical Trials (PRO-ACT) database with complete ALSFRS-R data (<i>n</i> = 888) at three time-points (Time 0, Time 1 (6-months), Time 2 (1-year)). Results demonstrated that in this population of 888 patients, mean age was 54.6 years, 64.4% were male, and 93.7% were Caucasian. The CFA supported a 4* individual-domain structure (bulbar, gross motor, fine motor, and respiratory domains). IRT analysis within each domain revealed misfitting items and overlapping item response category thresholds at all time-points, particularly in the gross motor and respiratory domain items. Results indicate that many of the items of the ALSFRS-R may sub-optimally distinguish among varying levels of disability assessed by each domain, particularly in patients with less severe disability. Measure performance improved across time as patient disability severity increased. In conclusion, modifications to select ALSFRS-R items may improve the instrument's specificity to disability level and sensitivity to treatment effects.

本研究旨在采用经典测试理论与现代测试理论方法，探究肌萎缩侧索硬化功能评定量表修订版（Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, ALSFRS-R）的维度结构与条目层面表现，并结合时间维度开展分析。本研究依托开放获取肌萎缩侧索硬化临床试验联合资源数据库（Pooled Resources Open-Access ALS Clinical Trials, PRO-ACT），纳入888名拥有完整ALSFRS-R数据的肌萎缩侧索硬化（amyotrophic lateral sclerosis, ALS）患者，在三个时间点（时间点0、时间点1（随访6个月）、时间点2（随访1年））开展验证性因子分析（Confirmatory Factor Analysis, CFA）与项目反应理论（Item Response Theory, IRT）分析。研究结果显示，该888名患者队列的平均年龄为54.6岁，男性占比64.4%，白种人占比93.7%。验证性因子分析结果支持ALSFRS-R存在4个独立维度结构，分别为球部功能、粗大运动、精细运动与呼吸功能维度。对各维度开展的项目反应理论分析显示，所有时间点下均存在条目拟合不佳的情况，且各条目反应类别阈值存在重叠，尤以粗大运动与呼吸功能维度的条目为甚。研究结果表明，ALSFRS-R的多数条目可能未能最优地区分各维度所评估的不同残疾程度，尤其针对残疾程度较轻的患者。随着患者残疾严重程度的升高，该量表的测评性能随随访时间推移有所提升。综上，针对部分ALSFRS-R条目进行修订，可提升该量表针对残疾水平的特异性以及对治疗效应的敏感性。