A multi-laboratory preclinical trial to assess treatment candidates for acute ischemic stroke

Human diseases may be modeled in animals to allow preclinical assessment of putative new clinical interventions. Recent, highly publicized failures of large clinical trials called into question the rigor, design, and value of preclinical assessment. We established the Stroke Preclinical Assessment Network (SPAN) to design and implement a randomized, controlled, blinded, multi-laboratory network for the rigorous assessment of candidate stroke treatments combined with intravascular thrombectomy. Futility boundaries in a Multi-Arm Multi-Stage statistical design aimed to exclude less effective interventions, and efficacy boundaries allowed early declaration of success after each of four sequential stages. Six independent research laboratories performed a standard focal cerebral ischemic insult in five animal models that included equal numbers of males and females: young mice, young rats, aging mice, mice with diet-induced obesity, and spontaneously hypertensive rats. The laboratories adhere..., SPAN consists of six research laboratories to conduct preclinical stroke modeling and a coordinating center to mask drugs, conduct centralized randomization, assess blinded outcomes, collect data, and perform statistics. The aim of SPAN was to determine whether such rigor is feasible and practical on a large scale in a multi-laboratory controlled, randomized preclinical study of six investigator-initiated putative interventions for acute ischemic stroke, selected through a rigorous NIH-peer review. Here we report the primary results of SPAN., Tables contain the results of the corner test and the MR imaging organized by subject ID. Treatment group data is available in the feasibility file. These are contained in the following files: dt_feasibility_stm_paper 2023-08-21dt_outcome_corner_stm_paper 2023-08-21dt_outcome_mri_stm_paper 2023-08-21report_stm_paper 2023-07-29 The first 3 files are Excel files that contain data listings in tab 1 and data definition dictionary in tab 2. The treatment group variables can be found in the first file and applied to the remaining files by matching on the animal identity variable \"enro_animal_id. The variable 'txas_tx_group' contains a code that gives the treatment group to which the subject was assigned. The variable 'txas_tx_group_actual' gives a code for the treatment group actually received. The corresponding drug treatment names can be found in tab 2 and in the main paper itself. The final html file is a report used to define the various study populations, including  the enrolled (pop_enr..., A multi-laboratory preclinical trial to assess treatment candidates for acute ischemic stroke --- All data needed for the graphs published in Science Translational Medicine are provided. ## Description of the data and file structure Tables contain the results of the corner test, the MR imaging organized by subject ID. Treatment group data is available in the feasibility file. These are contained in the following files: dt\_feasibility\_stm\_paper\_2023-08-21.xls dt\_outcome\_corner\_stm\_paper\_2023-08-21.xls dt\_outcome\_mri\_stm\_paper 2023-08-21.xls report\_stm\_paper\_2023-07-29.html The first 3 files are Excel files that contain data listings in tab 1 and data definition dictionay in tab 2. The treatment group variables can be found in the first file and applied to the remaining files by matching on the animal identity variable 'enro\_animal\_id'. The variable 'txas\_tx\_group' contains a code that gives the treatment group to which the subject was assigned. The variable 'txas...可通过动物模型模拟人类疾病，以对潜在新型临床干预手段开展临床前评估。近期备受关注的多项大型临床试验失败，令临床前评估的严谨性、设计合理性与应用价值受到质疑。 本研究组建了卒中临床前评估网络（Stroke Preclinical Assessment Network, SPAN），旨在搭建并运行一套随机、对照、盲法的多实验室网络体系，用于对联合血管内取栓术的卒中候选治疗方案开展严谨评估。该研究采用多臂多阶段统计设计，其无效性边界用于排除疗效欠佳的干预方案，而有效性边界则支持在四个连续阶段中的每个阶段完成后即可提前宣告试验成功。 六家独立研究实验室在五种雌雄数量均等的动物模型中实施了标准局灶性脑缺血造模：年轻小鼠、年轻大鼠、衰老小鼠、饮食诱导肥胖小鼠以及自发性高血压大鼠。各实验室遵循……；SPAN由六家负责卒中临床前造模的研究实验室，以及一家负责药物设盲、集中随机化、盲法结局评估、数据收集与统计分析的协调中心组成。 SPAN的研究目标为：在一项通过严格美国国立卫生研究院（National Institutes of Health, NIH）同行评议遴选的六项由研究者发起的急性缺血性卒中潜在干预方案的多实验室对照随机临床前研究中，验证此类严谨评估体系的大规模实施可行性与实用性。本研究报告SPAN的主要研究结果。 数据集表格包含转角试验结果与按受试者ID整理的磁共振成像（Magnetic Resonance, MR）结果。治疗组相关数据可在可行性文件中获取，具体包含以下文件： dt_feasibility_stm_paper_2023-08-21.xls dt_outcome_corner_stm_paper_2023-08-21.xls dt_outcome_mri_stm_paper_2023-08-21.xls report_stm_paper_2023-07-29.html 前3个文件均为Excel文件，其中第1工作表包含数据列表，第2工作表包含数据定义字典。治疗组变量可在首个文件中获取，并可通过动物识别变量"enro_animal_id"与其余文件进行匹配关联。变量"txas_tx_group"用于标注受试者被分配至的治疗组代码，变量"txas_tx_group_actual"则用于标注受试者实际接受的治疗组代码。对应的药物治疗名称可在第2工作表与主论文中查阅。最终的HTML文件为用于定义各类研究人群（包括已入组人群（pop_enr……））的报告。本研究为一项评估急性缺血性卒中候选治疗方案的多实验室临床前试验。 --- 本研究已提供《科学·转化医学（Science Translational Medicine）》刊发配图所需的全部数据。 ## 数据与文件结构说明 数据集表格包含转角试验结果与按受试者ID整理的磁共振成像结果。治疗组相关数据可在可行性文件中获取，具体包含以下文件： dt_feasibility_stm_paper_2023-08-21.xls dt_outcome_corner_stm_paper_2023-08-21.xls dt_outcome_mri_stm_paper_2023-08-21.xls report_stm_paper_2023-07-29.html 前3个文件均为Excel文件，其中第1工作表包含数据列表，第2工作表包含数据定义字典。治疗组变量可在首个文件中获取，并可通过动物识别变量"enro_animal_id"与其余文件进行匹配关联。变量"txas_tx_group"用于标注受试者被分配至的治疗组代码，变量"txas...