Patient experience and clinical outcome assessment validity in amyotrophic lateral sclerosis: a targeted literature review

To identify relevant concepts of measurement for people with amyotrophic lateral sclerosis (ALS) and to evaluate the face and content validity of clinical outcome assessments (COAs) that can be used to measure treatment benefits in ALS clinical trials.
A targeted literature review was conducted to explore patient experience (stage 1) and COAs used in ALS research (stage 2). Abstracts were screened against predefined eligibility criteria; full-text articles were reviewed for eligible abstracts and relevant data were extracted. Face and content validity of the identified COAs were assessed.
Stage 1 searches identified 3,527 abstracts, of which 12 full-text articles, two summary reports, and one conference poster were included in this review. Twenty-five symptoms and 35 health-related quality of life (HRQoL) impacts were identified. Frequently reported symptoms included breathing and speech difficulties and muscle/limb weakness, each associated with a diverse range of impacts, including those related to emotional wellbeing, physical function, social and leisure activities, and activities of daily living. Stage 2 searches identified 119 COAs, of which 28 were reviewed. Many had acceptable face (13/28) and content validity (15/28), but 13 had not involved patients during development; only 10 were clearly worded and seven were lengthy, increasing patient burden risk.
This review identified wide-ranging symptoms and HRQoL impacts experienced by people with ALS, but detailed qualitative evidence is sparse. Multiple COAs were identified as potential measures in ALS clinical trials.

本研究旨在明确肌萎缩侧索硬化（amyotrophic lateral sclerosis, ALS）患者相关的测量概念，并评估可用于ALS临床试验中衡量治疗获益的临床结局评估工具（clinical outcome assessments, COAs）的表面效度与内容效度。
本研究采用靶向文献综述法，分别于阶段1探索患者体验、阶段2梳理ALS相关研究中使用的COAs。研究首先依据预设的纳入排除标准筛选摘要，随后对符合条件的摘要对应的全文文献进行审阅并提取相关数据，同时对筛选出的COAs开展表面效度与内容效度评估。
阶段1的检索共获取3527篇摘要，最终纳入12篇全文文献、2份总结报告及1篇会议海报。本研究共识别出25项症状与35项健康相关生活质量（health-related quality of life, HRQoL）相关影响。常见报告的症状包括呼吸与言语困难、肌肉/肢体无力，上述症状均伴随多样化的相关影响，涉及情绪健康、躯体功能、社交与休闲活动及日常生活活动能力等多个维度。
阶段2的检索共识别出119项COAs，其中28项被纳入审阅。多数COAs具备可接受的表面效度（13/28）与内容效度（15/28），但其中13项在开发过程中未纳入患者参与；仅10项表述清晰明确，另有7项篇幅冗长，会增加患者的负担风险。
本综述明确了ALS患者所经历的广泛症状与HRQoL相关影响，但相关详细定性证据仍较为匮乏。本研究同时识别出多项可作为ALS临床试验潜在测量工具的COAs。