Stroke Center and Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Stroke. 2011 Aug;42(8):2356-62. doi: 10.1161/STROKEAHA.111.619122. Epub 2011 Jun 30.
Over the past decade, analysis of completed actual trials, model population studies, and theoretical work have improved approaches to selecting and analyzing end points in acute stroke treatment trials.
Narrative review.
Because stroke affects persons in their biological, functional, social, and experiential dimensions, measures of impairment, disability, handicap, and quality of life are all desirable in pivotal trials, with disability being most important. Scales that are valid, reliable, responsive, and easy to administer are preferred; consequently, the modified Rankin Scale has become the most widely used single clinical efficacy measure. Because stroke cripples and kills, most outcome scales array patient outcome in ordered ranks, spread over the entire range from normal to disabled to dead. Generally, shift analysis, analyzing all health state transitions concurrently, is the most efficient analytic technique to detect treatment effects, with sliding dichotomy less efficient and fixed dichotomy least efficient, unless treatment effects strongly cluster at 1 or a few health state transitions that can be prespecified. Test statistics must also take into account interpretability, ie, how well they can be converted into metrics capturing all outcomes the intervention might alter in proportion to the degree they are valued by the patient; full ordinal analysis is most informative, sliding dichotomy is intermediately informative, and fixed dichotomy is least informative regarding this global outcome.
Stroke trial power and interpretation can be substantially enhanced by adherence to the principles delineated in this review. Full ordinal and sliding dichotomy analysis will most often be advantageous compared with fixed dichotomous approaches.
在过去的十年中，对已完成的真实试验、模型人群研究和理论工作的分析改进了选择和分析急性脑卒中治疗试验终点的方法。
叙述性综述。
由于脑卒中影响患者的生物学、功能、社会和体验维度，因此在关键试验中，损伤、残疾、残障和生活质量的测量都是理想的，而残疾是最重要的。有效性、可靠性、响应性和易于管理的量表是首选的；因此，改良 Rankin 量表已成为最广泛使用的单一临床疗效测量方法。由于脑卒中使患者致残和死亡，大多数结局量表将患者的结局排列在有序的等级中，从正常到残疾到死亡。一般来说，移位分析同时分析所有健康状态的转变，是检测治疗效果最有效的分析技术，滑动二分法效率较低，固定二分法效率最低，除非治疗效果强烈集中在 1 个或几个可以预先指定的健康状态转变上。测试统计数据还必须考虑到可解释性，即它们如何能够转化为能够捕捉到干预措施可能改变的所有结果的指标，这些结果与患者重视的程度成正比；全序分析最具信息量，滑动二分法具有中等信息量，而固定二分法则关于这种整体结局信息量最低。
通过遵循本综述中阐述的原则，可以大大提高脑卒中试验的效力和解释。与固定二分法相比，全序和滑动二分法分析通常更有优势。
