% 0期刊文章%一个李薇薇安%巴普蒂斯特Leurent %弗雷德里克Barkhof %一个费伊卡弗蒂玛丽Braisher % %一个阿曼Eshaghi Olga Ciccarelli % %艾玛灰色%一个Mahesh Parmar詹妮弗·m·尼古拉斯% %一个Peryer %一个珍妮罗伯逊%奈杰尔消沉%詹姆斯沃森%一个杰里米Chataway % T设计多臂机多级自适应的神经保护试验进展型多发性硬化症% D R 10.1212 / WNL 2022%。0000000000200604 % J首页神经病学% P 754 - 764 V % 98% 18% N X显示很少有治疗残疾进展缓慢进展型多发性硬化症(PMS)。面临的挑战之一是有效地测试候选人的管道疗法临床前研究的临床试验。多臂机多级(播出)平台试验可能会加速评估新疗法比传统顺序临床试验。我们描述一个播出设计项目经理关注的临时和最终结果的措施,样本大小和统计方面的考虑。英国社会专家财团发展女士在最近的临床试验回顾女士经前综合症II和III期试验通知临时和最终结果选择和设计措施。模拟进行评价试验操作特征在不同治疗效果,招聘速度,和样本大小的假设。女士的人形成了一个病人和公众参与集团和导致了试验设计,确保满足女士的社区的需求。提出的设计评估3实验武器相比,一个共同的标准治疗手臂在2阶段。阶段1(临时)结果将全脑MRI在18个月萎缩,123年评估参与者每臂。脑萎缩治疗有足够证据放缓将继续第二阶段。 The stage 2 (final) outcome will be time to 6-month confirmed disability progression, based on a composite clinical score comprising the Expanded Disability Status Scale, Timed 25-Foot Walk test, and 9-Hole Peg Test. To detect a hazard ratio of 0.75 for this primary final outcome with 90% power, 600 participants per arm are required. Assuming one treatment progresses to stage 2, the trial will recruit ≈1,900 participants and last ≈6 years. This is approximately two-thirds the size and half the time of separate 2-arm phase II and III trials. The proposed MAMS trial design will substantially reduce duration and sample size compared to traditional clinical trials, accelerating discovery of effective treatments for PMS. The design was well-received by people with multiple sclerosis. The practical and statistical principles of MAMS trial design may be applicable to other neurodegenerative conditions to facilitate efficient testing of new therapies.9HPT=9-Hole Peg Test; EDSS=Expanded Disability Status Scale; MAMS=multi-arm multistage; MS=multiple sclerosis; PBVC=percentage of brain volume change; PMS=progressive multiple sclerosis; PPI=patient and public involvement; PPMS=primary progressive multiple sclerosis; RRMS=relapsing-remitting multiple sclerosis; SPMS=secondary progressive multiple sclerosis; T25FW=Timed 25-Foot Walk %U //www.ez-admanager.com/content/neurology/98/18/754.full.pdf