Improving power to detect disease progression in multiple sclerosis through alternative analysis strategies
Improving power to detect disease progression in multiple sclerosis through alternative analysis strategies
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DOI：
10.1007/s00415-011-6021-1
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发表时间：
2011-10-01
影响因子：
6
通讯作者：
Engler, David
中科院分区：
文献类型：
--
作者：
Healy, Brian;Chitnis, Tanuja;Engler, David
在多发性硬化症患者中，临床试验和观察性研究中对疾病进展的治疗效果的研究通常使用扩展残疾状态量表（EDSS）的持续进展作为结局。目前尚不清楚该结局是否是检测临床疾病进展治疗效果的最有效方法。EDSS模型选择对治疗效果检测的评估是值得关注的。该评估在三种潜在治疗效应下分别进行：降低未来EDSS升高几率的治疗、增加未来EDSS降低几率的治疗和导致两种效应的治疗。为了评估建模选择的效果，将九种建模策略应用于数据以确定最强大的方法。每隔6个月模拟EDSS测量24个月。每个患者的初始EDSS值范围在0和3之间，并且从一种EDSS状态转换到另一种EDSS状态的概率基于从可用临床数据获得的经验转换概率。无论治疗效果如何，基于持续进展的建模方法的效力低于直接建模EDSS评分的方法。当治疗效果对应于改善概率的增加时，这种差异尤其明显。与基于实际EDSS值的方法相比，EDSS上的持续进展是临床进展的较不有力的结局指标。
In patients with multiple sclerosis, investigation of a treatment effect on disease progression in clinical trials and observational studies often uses sustained progression on the expanded disability status scale (EDSS) as an outcome. It is not clear whether this outcome is the most powerful to detect a treatment effect on clinical disease progression. Assessment of EDSS modeling choice on the detection of treatment effect was of interest. This assessment was separately conducted under three potential treatment effects: treatment reducing the chance of higher future EDSS, treatment increasing the chance of lower future EDSS, and treatment leading to both effects. To assess the effect of modeling choice, nine modeling strategies were applied to the data to determine the most powerful approach. EDSS measurements were simulated at 6 month intervals for 24 months. Each patient's initial EDSS value ranged between 0 and 3, and probabilities of transitioning from one EDSS state to another were based on the empirical probabilities of transition obtained from available clinical data. Modeling approaches based on sustained progression had less power than approaches which modeled the EDSS score directly, regardless of treatment effect. This difference was especially pronounced when the treatment effect corresponded to an increase in the probability of improvement. Sustained progression on the EDSS is a less powerful outcome measure for clinical progression than approaches based on the actual EDSS values.