1,026 experimental treatments in acute stroke
1,026 experimental treatments in acute stroke
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DOI：
10.1002/ana.20741
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发表时间：
2006-03-01
影响因子：
11.2
通讯作者：
Howells, DW
中科院分区：
文献类型：
--
作者：
O'Collins, VE;Macleod, MR;Howells, DW
目的对神经保护剂进行临床前评价，以提高临床疗效。当不匹配时，就会出现这样的问题：实验是否是临床结果的不良指标，或者最好的药物是否没有进入临床试验。因此，我们建议对临床使用的药物和仅进行实验测试的药物进行实验效果和测试范围的对比。方法我们通过系统检索确定了神经保护剂和实验疗效报告。选择使用功能或组织学终点的体内和体外对照实验进行分析。结果之间的关系，药物机制，测试范围和临床试验状态进行了统计学评估。结果没有证据表明临床使用的药物（114种药物）比仅在动物模型中测试的药物（912种药物）更有效，例如，局灶模型的平均改善分别为31.3 ± 16.7%和24.4 ± 32.9%，p > 0.05。使用中风治疗学术行业圆桌会议（STAIR）标准的测试范围是高度可变的，并且没有发现机制和疗效之间的关系。口译。结果质疑是否最有效的药物被选择用于中风临床试验。这可能部分解释了治疗进展缓慢的原因。在动物数据的处理、报告和分析方面更加严格，将促进科学进步从实验室到临床的转变。
Objective Preclinical evaluation of neuroprotectants fostered high expectations of clinical efficacy. When not matched, the question arises whether experiments are poor indicators of clinical outcome or whether the best drugs were not taken forward to clinical trial. Therefore, we endeavored to contrast experimental efficacy and scope of testing of drugs used clinically and those tested only experimentally. Methods We identified neuroprotectants and reports of experimental efficacy via a systematic search. Controlled in vivo and in vitro experiments using functional or histological end points were selected for analysis. Relationships between outcome, drug mechanism, scope of testing, and clinical trial status were assessed statistically. Results There was no evidence that drugs used clinically (114 drugs) were more effective experimentally than those tested only in animal models (912 drugs), for example, improvement in focal models averaged 31.3 +/- 16.7% versus 24.4 +/- 32.9%, p > 0.05, respectively. Scope of testing using Stroke Therapy Academic Industry Roundtable (STAIR) criteria was highly variable, and no relationship was found between mechanism and efficacy. Interpretation. The results question whether the most efficacious drugs are being selected for stroke clinical trials. This may partially explain the slow progress in developing treatments. Greater rigor in the conduct, reporting, and analysis of animal data will improve the transition of scientific advances from bench to bedside.