PDF(Pubmed)
Abstract：
This study was undertaken to evaluate how the challenges in the recruitment and retention of participants in clinical trials for focal onset epilepsy have changed over time.
In this systematic analysis of randomized clinical trials of adjunct antiseizure medications for medication-resistant focal onset epilepsy, we evaluated how the numbers of participants, sites, and countries have changed since the first such trial in 1990. We also evaluated the proportion of participants who completed each trial phase and their reasons for early trial exit. We analyzed these trends using mixed effects generalized linear models accounting for the influence of the number of trial sites and trial-specific variability.
The number of participants per site has steadily decreased over decades, with recent trials recruiting fewer than five participants per site (reduction by .16 participants/site/year, p < .0001). Fewer participants also progressed from recruitment to randomization over time (odds ratio = .94/year, p = .014). Concurrently, there has been an increase in the placebo response over time (increase in median percent reduction of .4%/year, p = .02; odds ratio of increase in 50% responder rate of 1.03/year, p = .02), which was not directly associated with the number of sites per trial (p > .20).
This historical analysis highlights the increasing challenges with participant recruitment and retention, as well as increasing placebo response. It serves as a call to action to change clinical trial design to address these challenges.
In this systematic analysis of randomized clinical trials of adjunct antiseizure medications for medication-resistant focal onset epilepsy, we evaluated how the numbers of participants, sites, and countries have changed since the first such trial in 1990. We also evaluated the proportion of participants who completed each trial phase and their reasons for early trial exit. We analyzed these trends using mixed effects generalized linear models accounting for the influence of the number of trial sites and trial-specific variability.
The number of participants per site has steadily decreased over decades, with recent trials recruiting fewer than five participants per site (reduction by .16 participants/site/year, p < .0001). Fewer participants also progressed from recruitment to randomization over time (odds ratio = .94/year, p = .014). Concurrently, there has been an increase in the placebo response over time (increase in median percent reduction of .4%/year, p = .02; odds ratio of increase in 50% responder rate of 1.03/year, p = .02), which was not directly associated with the number of sites per trial (p > .20).
This historical analysis highlights the increasing challenges with participant recruitment and retention, as well as increasing placebo response. It serves as a call to action to change clinical trial design to address these challenges.
摘要：
目的：评估局灶性发作癫痫临床试验参与者的招募和保留方面的挑战如何随时间变化。
方法：在对耐药局灶性癫痫发作的辅助抗癫痫药物的随机临床试验的系统分析中，我们评估了参与者的数量，网站,自1990年第一次这样的审判以来，各国都发生了变化。我们还评估了完成每个试验阶段的参与者比例以及他们提前退出试验的原因。我们使用混合效应广义线性模型分析了这些趋势，该模型考虑了试验地点数量和试验特定变异性的影响。
结果：几十年来，每个站点的参与者数量稳步下降，最近的试验每个站点招募的参与者少于5人（每年减少0.16名参与者/站点，p<0.0001)。随着时间的推移，从招募到随机化的参与者也越来越少(赔率比0.94/年，p=0.014)。同时,随着时间的推移，安慰剂的反应有所增加(年增长率为0.4%，p=0.02；50%应答率增加1.03/年的赔率比，p=0.02),这与每个试验的站点数量没有直接相关（p>0.20）。
结论：这一历史分析凸显了参与者招募和保留方面日益严峻的挑战，以及增加安慰剂反应。它呼吁采取行动，改变临床试验设计，以应对这些挑战。
方法：在对耐药局灶性癫痫发作的辅助抗癫痫药物的随机临床试验的系统分析中，我们评估了参与者的数量，网站,自1990年第一次这样的审判以来，各国都发生了变化。我们还评估了完成每个试验阶段的参与者比例以及他们提前退出试验的原因。我们使用混合效应广义线性模型分析了这些趋势，该模型考虑了试验地点数量和试验特定变异性的影响。
结果：几十年来，每个站点的参与者数量稳步下降，最近的试验每个站点招募的参与者少于5人（每年减少0.16名参与者/站点，p<0.0001)。随着时间的推移，从招募到随机化的参与者也越来越少(赔率比0.94/年，p=0.014)。同时,随着时间的推移，安慰剂的反应有所增加(年增长率为0.4%，p=0.02；50%应答率增加1.03/年的赔率比，p=0.02),这与每个试验的站点数量没有直接相关（p>0.20）。
结论：这一历史分析凸显了参与者招募和保留方面日益严峻的挑战，以及增加安慰剂反应。它呼吁采取行动，改变临床试验设计，以应对这些挑战。
