Reliability of Outcome Measures in Clinical Trials in Secondary Progressive Multiple Sclerosis
Reliability of Outcome Measures in Clinical Trials in Secondary Progressive Multiple Sclerosis
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DOI：
10.1212/wnl.0000000000011123
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发表时间：
2021-01-05
期刊：
影响因子：
9.9
通讯作者：
Cutter, Gary
中科院分区：
文献类型：
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作者：
Koch, Marcus W.;Mostert, Jop;Cutter, Gary
目的为探讨继发性进展性多发性硬化症(SPMS)临床试验结果的可靠性，我们比较了2个大型随机对照试验(RCT)数据集中安慰剂组中不同临床结果指标的进展和改善事件的频率。方法使用来自IMPACT(国际MS继发性进展性Avonex对照试验)和ASCED(那他珠单抗对降低继发性进展性多发性硬化症参与者残疾进展的有效性的临床研究)、SPMS中的两个大型随机对照试验的原始试验数据，我们比较了在扩展残疾状况量表(EDSS)、计时25英尺步行(T25FW)、9-Hole Peg试验(9HPT)及其组合的情况下，在3个月或6个月的结果指标确认的情况下残疾进展和类似定义的改善。结果在两组数据中，EDSS随时间推移的改善率最高，进展率和改善率之间的差异最小，其次是T25FW和9HPT。对于T25FW和9HPT，随着时间的推移，改善率相当稳定，保持在10%以下或左右的水平。对于EDSS，改善率与残疾进展率同步增加。结论SPMS中所有被调查的结果指标都显示出一些随机变异和测量误差的证据，T25FW和9HPT比更确定的结果EDSS更小。我们的发现对SPMS试验的设计和批判性评估具有重要意义。
Objective To investigate the reliability of clinical outcomes in secondary progressive multiple sclerosis (SPMS) trials, we compared the frequency of progression and improvement events on different clinical outcome measures in the placebo arms of 2 large randomized controlled trial (RCT) datasets. Methods Using original trial data from the placebo arms of IMPACT (International MS Secondary Progressive Avonex Controlled Trial) and ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis), 2 large RCTs in SPMS, we compared disability progression and similarly defined improvement with and without 3- or 6-month confirmation on the outcome measures Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and their combinations. Results In both datasets, the EDSS showed the highest rates of improvement over time, and the smallest difference between progression and improvement rates, followed by the T25FW and the 9HPT. For the T25FW and 9HPT, improvement rates were fairly stable over time and remained at below or around the 10% level. For the EDSS, improvement rates increased in parallel with disability progression rates. Conclusions All investigated outcome measures in SPMS showed some evidence of random variation and measurement error, the T25FW and 9HPT less so than the more established outcome EDSS. Our findings are relevant for the design and critical appraisal of trials in SPMS.