Developing a Natural History Progression Model for Duchenne Muscular Dystrophy Using the Six-Minute Walk Test.
Developing a Natural History Progression Model for Duchenne Muscular Dystrophy Using the Six-Minute Walk Test.
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DOI：
10.1002/psp4.12220
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发表时间：
2017-09
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影响因子：
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通讯作者：
AbuTarif M
中科院分区：
文献类型：
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作者：
Hamuro L;Chan P;Tirucherai G;AbuTarif M
6 分钟步行测试 (6MWT) 被用作杜氏肌营养不良症 (DMD) 试验中评估药物疗效的临床终点。使用数字化 6MWT 数据开发了一个模型，该模型估计两个斜率和两个截距，以表征开发过程中 6MWT 的改进和 6MWT 的下降。平均基线 6MWT 为 362 (±87) 米。该模型预测，直到 10 岁（95% CI = 6.78–13.1）之前，将以 20 米/年（95% 置信区间 (CI) = 9.4–30）的速度进步，然后以 85 米/年的速度下降（95% CI = 72–98）。改善和下降的患者间斜率变异性相似，变异系数百分比 (%CV) 和 23.3%CV 分别为 21.9% 和 23.3%CV。使用先前 DMD 自然历史研究中的年龄人口统计数据进行的模型模拟可以合理预测 6MWT 的改善和下降趋势。该模型可用于量化个体患者轨迹、确定疾病进展的预后因素以及评估药物效果。
The 6‐minute walk test (6MWT) is used as a clinical endpoint to evaluate drug efficacy in Duchenne Muscular Dystrophy (DMD) trials. A model was developed using digitized 6MWT data that estimated two slopes and two intercepts to characterize 6MWT improvement during development and 6MWT decline. Mean baseline 6MWT was 362 (±87) meters. The model predicted an improvement at a rate of 20 meters/year (95% confidence interval (CI) = 9.4–30) up until 10 years old (95% CI = 6.78–13.1), and then a decline at a rate of 85 meters/year (95% CI = 72–98). Interpatient slope variability for improvement and decline were similar at 21.9 percentage of coefficient of variation (%CV) and 23.3%CV, respectively. Model simulations using age demographics from a previous DMD natural history study could reasonably predict the trend in improvement and decline in the 6MWT. This model can be used to quantitate individual patient trajectories, identify prognostic factors for disease progression, and evaluate drug effect.