Gordon Paul H, Cheng Bin, Montes Jacqueline, Doorish Carolyn, Albert Steven M, Mitsumoto Hiroshi
Department of Neurology, The Eleanor and Lou Gehrig MDA/ALS Research Center, College of Physicians and Surgeons, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
Amyotroph Lateral Scler. 2007 Oct;8(5):270-3. doi: 10.1080/17482960701547958.
As the number of potential neuroprotective agents for ALS increases, the need for early phase trials that screen drugs before proceeding to efficacy trials also grows. However, it is not known which outcome measures perform best and also provide the most meaningful information in brief small trials. We assessed the performance of different outcome measures for use in early phase clinical trials in ALS, and determined what degree of change in the ALSFRS-R that patients could perceive. Thirty patients underwent six monthly ALS Functional Rating Scale (ALSFRS-R), forced vital capacity, manual muscle testing (MMT) and quality of life assessments. Patients rated their perceived level of change with algorithm scales. Linear mixed effects models assessed the associations among variables and Cox proportional-hazards models examined the ability to predict survival. The quantity of missing data was assessed using descriptive statistics. Correlations were found between all variables. The ALSFRS-R provided the most complete data (99.5%), showed a large within-subject correlation (0.91), and best predicted survival (p = 0.002). One-unit change in patient-perceived clinical function paralleled a 9-point decrease in the ALSFRS-R (p = 0.025; 95% CI 8, 10). This trial assessed just 30 patients over six months, but the standard outcome measures each performed dependably; all could be used in short-duration, early phase trials. The ALSFRS-R most strongly predicted survival and provided the most complete data, but large changes may be necessary before patients perceive treatment effects.
随着用于肌萎缩侧索硬化症（ALS）的潜在神经保护剂数量的增加，在进行疗效试验之前筛选药物的早期试验的需求也在增长。然而，尚不清楚哪些结果指标在简短的小型试验中表现最佳且能提供最有意义的信息。我们评估了用于ALS早期临床试验的不同结果指标的性能，并确定了患者能够察觉到的ALS功能评定量表修订版（ALSFRS-R）的变化程度。30名患者每六个月接受一次ALS功能评定量表（ALSFRS-R）、用力肺活量、徒手肌力测试（MMT）和生活质量评估。患者使用算法量表对他们察觉到的变化程度进行评分。线性混合效应模型评估变量之间的关联，Cox比例风险模型检验预测生存的能力。使用描述性统计评估缺失数据的数量。发现所有变量之间均存在相关性。ALSFRS-R提供了最完整的数据（99.5%），显示出较大的受试者内相关性（0.91），并且对生存的预测最佳（p = 0.002）。患者察觉到的临床功能变化一个单位相当于ALSFRS-R下降9分（p = 0.025；95%置信区间8, 10）。该试验在六个月内仅评估了30名患者，但每个标准结果指标的表现都可靠；所有指标均可用于短期的早期试验。ALSFRS-R对生存的预测最强且提供了最完整的数据，但在患者察觉到治疗效果之前可能需要有较大的变化。
