Shan Guogen, Banks Sarah, Miller Justin B, Ritter Aaron, Bernick Charles, Lombardo Joseph, Cummings Jeffrey L
Epidemiology and Biostatistics Program, Department of Environmental and Occupational Health School of Community Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA.
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
Alzheimers Dement (N Y). 2018 Jun 14;4:366-371. doi: 10.1016/j.trci.2018.04.006. eCollection 2018.
New treatments for neurodegenerative disease are urgently needed, and clinical trial methods are an essential component of new drug development. Although a parallel-group study design for neurological disorder clinical trials is commonly used to test the effectiveness of a new treatment as compared to placebo, it does not efficiently use information from the on-going study to increase the success rate of a trial or to stop a trial earlier when the new treatment is indeed ineffective.
We review some recent advances in designs for clinical trials, including futility designs and adaptive designs.
Futility designs and noninferiority designs are used to test the nonsuperiority and the noninferiority of a new treatment, respectively. We provide some guidance on using these two designs and analyzing data from these studies properly. Adaptive designs are increasingly used in clinical trials to improve the flexibility and efficiency of trials with the potential to reduce resources, time, and costs. We review some typical adaptive designs and new statistical methods to handle the statistical challenges from adaptive designs.
Statistical advances in clinical trial designs may be helpful to shorten study length and benefit more patients being treated with a better treatment during the discovery of new therapies for neurological disorders. Advancing statistical underpinnings of neuroscience research is a critical aspect of the core activities supported by the Center of Biomedical Research Excellence award supporting the Center for Neurodegeneration and Translational Neuroscience.
神经退行性疾病急需新的治疗方法，而临床试验方法是新药研发的重要组成部分。尽管在神经系统疾病临床试验中，平行组研究设计通常用于测试新治疗方法相对于安慰剂的有效性，但它无法有效利用正在进行的研究中的信息来提高试验成功率，也无法在新治疗方法确实无效时更早地终止试验。
我们回顾了临床试验设计方面的一些最新进展，包括无效性设计和适应性设计。
无效性设计和非劣效性设计分别用于测试新治疗方法的非优越性和非劣效性。我们提供了关于使用这两种设计以及正确分析这些研究数据的一些指导。适应性设计在临床试验中越来越多地被使用，以提高试验的灵活性和效率，有可能减少资源、时间和成本。我们回顾了一些典型的适应性设计以及应对适应性设计带来的统计挑战的新统计方法。
临床试验设计中的统计学进展可能有助于缩短研究时长，并在神经疾病新疗法的发现过程中，让更多患者受益于更好的治疗。推进神经科学研究的统计学基础是卓越生物医学研究中心奖所支持的核心活动的一个关键方面，该奖项支持神经退行性疾病与转化神经科学中心。
