TY -的T1 -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JF -神经学乔-神经病学SP - 754 LP - 764 - 10.1212 / WNL。首页0000000000200604六世- 98 - 18 AU -薇薇安李盟-巴普蒂斯特Leurent AU -弗雷德里克Barkhof AU -玛丽Braisher盟费伊卡弗蒂Arman Eshaghi AU -奥尔加Ciccarelli盟盟詹尼弗·m·尼古拉斯-艾玛灰色盟盟- Mahesh Parmar盟人Peryer AU -珍妮罗伯逊盟奈杰尔消沉的非盟-詹姆斯沃森盟杰里米Chataway Y1 - 2022/05/03 UR - //www.ez-admanager.com/content/98/18/754.abstract N2 -很少有治疗证明残疾进展缓慢进展型多发性硬化症(PMS)。首页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。 Treatments with sufficient evidence for slowing brain atrophy will continue to the second stage. 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 ER -