Kahle Michael P, Bix Gregory J
Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, Bryan, TX 77807, USA ; Sanders-Brown Center on Aging and Department of Anatomy and Neurobiology, University of Kentucky, 430 Sanders Brown Building 800 S. Limestone Street, Lexington, KY 40536, USA.
Stroke Res Treat. 2012;2012:374098. doi: 10.1155/2012/374098. Epub 2012 Dec 30.
The Stroke Therapy Academic Industry Roundtable (STAIR) provided initial (in 1999) and updated (in 2009) recommendations with the goal of improving preclinical stroke therapy assessment and to increase the translational potential of experimental stroke treatments. It is important for preclinical stroke researchers to frequently consider and revisit these concepts, especially since promising experimental stroke treatments continue to fail in human clinical trials. Therefore, this paper will focus on considerations for several key aspects of preclinical stroke studies including the selection and execution of the animal stroke model, drug/experimental treatment administration, and outcome measures to improve experimental validity and translation potential. Specific points of interest discussed include the incorporation of human comorbid conditions and drugs, the benefits of defining a proposed mechanism of action, replication of results using multiple methods, using clinically relevant routes of administration and treatment time windows, and performing and reporting good experimental methods to reduce bias such as, as suggested by the updated STAIR recommendations, sample size calculations, randomization, allocation concealment, blinding, and appropriate inclusion/exclusion criteria. It is our hope that reviewing and revisiting these considerations will benefit researchers in their investigations of stroke therapies and increase the likelihood of translational success in the battle against stroke.
中风治疗学术产业圆桌会议(STAIR)在1999年提出了初步建议,并于2009年进行了更新,目的是改善临床前中风治疗评估,并提高实验性中风治疗的转化潜力。对于临床前中风研究人员来说,经常考虑和重新审视这些概念很重要,特别是因为有前景的实验性中风治疗在人类临床试验中仍不断失败。因此,本文将重点关注临床前中风研究几个关键方面的考量因素,包括动物中风模型的选择与实施、药物/实验性治疗的给药方式以及改善实验有效性和转化潜力的结果测量指标。讨论的具体关注点包括纳入人类合并症和药物、明确拟议作用机制的益处、使用多种方法复制结果、采用临床相关的给药途径和治疗时间窗,以及按照更新后的STAIR建议进行并报告良好的实验方法以减少偏倚,如样本量计算、随机化、分配隐藏、盲法以及适当的纳入/排除标准。我们希望回顾和重新审视这些考量因素将有助于研究人员开展中风治疗研究,并增加在对抗中风斗争中实现转化成功的可能性。