BACKGROUND We recently compared clinical outcomes in secondary progressive MS (SPMS) clinical trials and found an association of timed 25 foot walk (T25FW) worsening events and baseline disability scores. It is unclear whether disability worsening in clinical trials is comparable to that seen in clinical practice. OBJECTIVE The objective of this study is to compare disability worsening between the IMPACT and ASCEND data sets and data from the Calgary MS clinic and to characterize the association of baseline T25FW and expanded disability status scale (EDSS) scores with disability worsening. METHODS We combined the three data sets and investigated the impact of baseline characteristics on disability worsening with a logistic regression model. We calculated T25FW, EDSS, and 'EDSS or T25FW' worsening events as a function of ascending cut-off baseline disability scores. RESULTS Data source was not associated with T25FW worsening at 12 months. There was a strong association of baseline T25FW and EDSS cut-off scores with T25FW worsening. No such association was present for the EDSS and 'EDSS or T25FW'. CONCLUSION Our results suggest that it is possible to 'enrich' a trial cohort for expected T25FW worsening events using specific baseline T25FW and EDSS cut-off scores. These analyses inform the selection of inclusion criteria for clinical trials in SPMS.

中文翻译：

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SPMS 临床试验的丰富策略

背景我们最近比较了继发性进展性 MS (SPMS) 临床试验的临床结果，发现定时 25 英尺步行 (T25FW) 恶化事件与基线残疾评分之间存在关联。目前尚不清楚临床试验中的残疾恶化是否与临床实践中看到的相似。目的 本研究的目的是比较 IMPACT 和 ASCEND 数据集与来自卡尔加里 MS 诊所的数据之间的残疾恶化情况，并描述基线 T25FW 和扩展残疾状态量表 (EDSS) 评分与残疾恶化之间的关联。方法我们结合了三个数据集，并使用逻辑回归模型研究了基线特征对残疾恶化的影响。我们计算了 T25FW、EDSS 和“EDSS 或 T25FW” 恶化事件作为上升截止基线残疾评分的函数。结果 数据来源与 12 个月时 T25FW 恶化无关。基线 T25FW 和 EDSS 临界值与 T25FW 恶化有很强的相关性。EDSS 和“EDSS 或 T25FW”不存在此类关联。结论 我们的结果表明，可以使用特定的基线 T25FW 和 EDSS 截止分数“丰富”预期 T25FW 恶化事件的试验队列。这些分析为选择 SPMS 临床试验的纳入标准提供了依据。结论 我们的结果表明，可以使用特定的基线 T25FW 和 EDSS 截止分数“丰富”预期 T25FW 恶化事件的试验队列。这些分析为选择 SPMS 临床试验的纳入标准提供了依据。结论 我们的结果表明，可以使用特定的基线 T25FW 和 EDSS 截止分数“丰富”预期 T25FW 恶化事件的试验队列。这些分析为选择 SPMS 临床试验的纳入标准提供了依据。