Nicholson Katharine A, Cudkowicz Merit E, Berry James D
Massachusetts General Hospital, Department of Neurology, Neurological Clinical Research Institute, 165 Cambridge Street, Suite 600, Boston, MA, 02114, USA,
Neurotherapeutics. 2015 Apr;12(2):376-83. doi: 10.1007/s13311-015-0341-2.
The last 2 decades have seen a surge in the number of amyotrophic lateral sclerosis (ALS) clinical trials with the hope of finding successful treatments. Clinical trialists aim to repurpose existing drugs and test novel compounds to target potential ALS disease pathophysiology. Recent technological advancements have led to the discovery of new causative genetic agents and modes of delivering potential therapy, calling for increasingly sophisticated trial design. The standard ALS clinical trial design may be modified depending on study needs: type of therapy; route of therapy delivery; phase of therapy development; applicable subpopulation; market availability of therapy; and utility of telemedicine. Novel biomarkers of diagnostic, predictive, prognostic, and pharmacodynamic value are undergoing development and validation for use in clinical trials. Design modifications build on the traditional clinical trial design and may be employed in either the learning or confirming trial phase. Novel designs aim to minimize patient risk, study duration, and sample size, while improving efficiency and promoting statistical power to herald an exciting era for clinical research in ALS.
在过去20年里，肌萎缩侧索硬化症（ALS）临床试验的数量激增，人们希望能找到成功的治疗方法。临床试验人员旨在重新利用现有药物，并测试新型化合物，以针对潜在的ALS疾病病理生理学。最近的技术进步已促成新的致病基因因素的发现以及潜在治疗方法的递送模式，这就需要越来越复杂的试验设计。标准的ALS临床试验设计可能会根据研究需求进行修改：治疗类型；治疗递送途径；治疗开发阶段；适用的亚组人群；治疗的市场可及性；以及远程医疗的效用。具有诊断、预测、预后和药效学价值的新型生物标志物正在开发和验证中，以便用于临床试验。设计修改基于传统的临床试验设计，可用于探索性试验阶段或确证性试验阶段。新颖的设计旨在将患者风险、研究持续时间和样本量降至最低，同时提高效率并增强统计效力，从而开创ALS临床研究的一个激动人心的时代。
