Objective

Clinical trials typically report antiepileptic drug efficacy by evaluating reduction in monthly convulsive seizure frequency (MCSF) through group response (active versus placebo). Although useful for regulatory purposes, population statistics do not easily translate into clinical practice, where treatment decisions are made on an individual-patient basis. Responder analyses help bridge this gap by showing proportions of patients who achieved various MCSF improvement levels. Deriving numbers needed to treat (NNTs) to achieve clinically desirable response levels can further inform individual decision-making. We calculated the NNT with fenfluramine to achieve “clinically meaningful” (≥50%) or “profound” (≥75%) MCSF reductions in patients with Dravet syndrome (DS).

Methods

NNT to achieve ≥50% or ≥75% MCSF reduction was assessed using longitudinal data from two phase 3 studies for adjunctive fenfluramine in DS patients aged 2–18 years. NNT was calculated: 1/((Experimental-Responder Rate)−(Control-Responder Rate)).

Results

In Study 1, NNTs to achieve ≥50% and ≥75% MCSF reduction were 1.8 and 2.1 at 0.7 mg/kg/day fenfluramine. In Study 2, these NNTs were 2.0 and 3.1, respectively. These results were seen as early as Weeks 6–7 and were sustained through Weeks 14–15.

Interpretation

For every two to three patients with DS treated with fenfluramine in these trials, one patient achieved ≥50% or ≥75% MCSF reduction, respectively, compared with placebo (large treatment effect size; Cohen’s d≈0.8). Responder analyses and NNTs can aid in clinical decision-making by offering clinically important information that is complementary to the population mean data on the chance of an individual patient achieving meaningful levels of MCSF improvement.

(NCT02682927/NCT02826863, NCT02926898)

中文翻译：

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芬氟拉明响应者分析和治疗所需数字：将癫痫试验数据转化为临床实践

目的

临床试验通常通过评估小组反应（活性药物与安慰剂药物）的每月惊厥发作频率（MCSF）的降低来报告抗癫痫药的疗效。尽管对于监管目的很有用，但是人口统计数据并不容易转化为临床实践，在临床实践中，治疗决策是基于个人患者的。响应者分析通过显示达到各种MCSF改善水平的患者比例来帮助弥合这一差距。达到临床所需的反应水平所需的治疗（NNT）所需的推导数可以进一步为个体决策提供依据。我们用芬氟拉明计算了NNT，以使Dravet综合征（DS）患者的MCSF降低“具有临床意义”（≥50％）或“深刻”（≥75％）。

方法

使用两项3至3岁辅助芬氟拉明的3期临床研究的纵向数据，评估了达到≥50％或≥75％MCSF降低的NNT。计算出NNT：1 /（（（实验-响应率）-（控制-响应率））。

结果

在研究1中，在0.7 mg / kg /天的芬氟拉明下，达到≥50％和≥75％MCSF降低的NNT为1.8和2.1。在研究2中，这些NNT分别为2.0和3.1。这些结果最早可在第6-7周发现，并持续到14-15周。

解释

在这些试验中，每两到三名接受芬氟拉明治疗的DS患者，与安慰剂相比，其MCSF降低分别达到≥50％或≥75％（较大的治疗效果； Cohend≈0.8）。响应者分析和NNT可以通过提供与重要的临床信息相辅相成的临床重要信息来辅助临床决策，这些信息是有关单个患者实现有意义的MCSF改善水平的机会的总体平均值。

（NCT02682927 / NCT02826863，NCT02926898）