Can we eliminate placebo in ALS clinical trials?
Can we eliminate placebo in ALS clinical trials?
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DOI：
10.1080/14660820310006661
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Stromatt, SC
中科院分区：
文献类型：
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作者：
Bryan, WW;Hoagland, RJ;Stromatt, SC
背景：先前的研究得出的结论是，肌萎缩性侧索硬化症患者（ALS）的强度下降是线性功能。如果是这样，在临床试验中，患者的自然病史可能是对照而不是安慰剂。每月测量每个患者的强制生命力（FVC）评分和最大自愿等轴测收缩（MVIC）原始得分（MVIC）原始分数，标准化并平均为Megascores。对于138名患者，比较了自然历史阶段和安慰剂阶段的手臂，腿，FVC，手臂+腿组合以及臂+腿+FVC组合巨型斜坡。分泌物：自然历史阶段中的巨型坡度的平均斜率在安慰剂阶段的平均斜率在手臂，腿部和胳膊+腿的巨像中没有差异，但FVC和ARM+腿+FVC组合有所不同Megascores.Conclusions：自然历史控制可能在使用ARM Megascore斜率作为主要结果度量的ALS探索性试验中很有用。但是，使用自然历史控制有明显的局限性，因此第3阶段ALS临床试验需要安慰剂控制。
BACKGROUND: Previous studies concluded that the decline in strength in patients with amyotrophic lateral sclerosis (ALS) is a linear function. If so, a patient's natural history might serve as the control, instead of placebo, in a clinical trial.METHODS: A placebo-controlled ALS clinical trial included a natural history phase, followed by a 6-month treatment phase. Each patient's forced vital capacity (FVC) score and maximal voluntary isometric contraction (MVIC) raw scores were measured monthly, standardized, and averaged into megascores. For 138 patients, the arm, leg, FVC, arm+leg combination, and arm+leg+FVC combination megascore slopes during the natural history phase and during the placebo phase were compared.RESULTS: The mean slope of megascores during the natural history phase and the mean slope during the placebo phase were not different for the arm, leg, and arm+leg megascores, but were different for the FVC and arm+leg+FVC combination megascores.CONCLUSIONS: Natural history controls may be useful in ALS exploratory trials that use arm megascore slope as the primary outcome measure. However, there are distinct limitations to the use of natural history controls, so that Phase 3 ALS clinical trials require placebo controls.