论文标题

多种治疗选择的异质效应的两个阶段预测模型:将药物应用于多发性硬化症

A two-stage prediction model for heterogeneous effects of many treatment options: application to drugs for Multiple Sclerosis

论文作者

Chalkou, Konstantina, Steyerberg, Ewout, Egger, Matthias, Manca, Andrea, Pellegrini, Fabio, Salanti, Georgia

论文摘要

不同患者的治疗效果各不相同,并且对这种变异性的估计对于临床决策很重要。目的是开发一个模型,以估算个别患者的替代治疗选择的好处。因此,我们通过在单个患者数据可用时结合预后研究和网络荟萃分析方法,开发了一个两阶段的预测模型,通过结合预后研究和网络荟萃分析。在第一阶段,我们开发了预后模型,并预测结果的基线风险。在第二阶段,我们将此基线风险得分从第一阶段用作网络元回归模型中的单个预后因素和效应修饰符。我们将方法应用于三项随机临床试验的网络荟萃分析,该试验比较了Natalizumab,Glatiramer乙酸盐和富马酸二甲酯的复发率,其中包括3590例诊断为诊断患有复发性多发性硬化症的患者。我们发现基线风险评分改变了相对和绝对治疗效果。年龄和残疾状况等几种患者特征对基线复发风险的影响,这反过来又节省了每种治疗方法可能预期的好处。对于高危患者而言,将两年内复发风险降至最低的治疗方法是纳塔尔苏单抗,而对于低风险的患者,富马酸二甲酯二甲酸二甲酸二甲酸二甲酸二甲酸酯可能是更好的选择。我们的方法很容易扩展到所有感兴趣的结果,并有可能告知个性化治疗方法。

Treatment effects vary across different patients and estimation of this variability is important for clinical decisions. The aim is to develop a model to estimate the benefit of alternative treatment options for individual patients. Hence, we developed a two-stage prediction model for heterogeneous treatment effects, by combining prognosis research and network meta-analysis methods when individual patient data is available. In a first stage, we develop a prognostic model and we predict the baseline risk of the outcome. In the second stage, we use this baseline risk score from the first stage as a single prognostic factor and effect modifier in a network meta-regression model. We apply the approach to a network meta-analysis of three randomized clinical trials comparing the relapse rate in Natalizumab, Glatiramer Acetate and Dimethyl Fumarate including 3590 patients diagnosed with relapsing-remitting multiple sclerosis. We find that the baseline risk score modifies the relative and absolute treatment effects. Several patient characteristics such as age and disability status impact on the baseline risk of relapse, and this in turn moderates the benefit that may be expected for each of the treatments. For high-risk patients, the treatment that minimizes the risk to relapse in two years is Natalizumab, whereas for low-risk patients Dimethyl Fumarate Fumarate might be a better option. Our approach can be easily extended to all outcomes of interest and has the potential to inform a personalised treatment approach.

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