Finding the most powerful measures of the effectiveness of tissue plasminogen activator in the NINDS tPA Stroke Trial
Finding the most powerful measures of the effectiveness of tissue plasminogen activator in the NINDS tPA Stroke Trial
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DOI：
10.1161/01.str.31.10.2335
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发表时间：
2000-10-01
期刊：
影响因子：
8.3
通讯作者：
Frankel, M
中科院分区：
文献类型：
--
作者：
Broderick, JP;Lu, M;Frankel, M
背景与目的：在美国国家神经疾病与卒中研究所（NINDS） rTPA卒中试验中，我们试图确定组织纤溶酶原激活剂（tPA）治疗效果的最有效的二元指标。方法：使用分类与回归树（CART）算法，我们在治疗后4次评估NINDS tPA卒中试验中的4种临床量表和头部CT成像指标的二元切点和二元切点组合：2小时、24小时、7 ~ 10天、3个月。第一个分析侧重于使用来自2小时和24小时临床和放射学测量的结果测量来检测tPA“早期活动”的证据，第二个分析侧重于长期结果和“疗效”，并使用来自7至10天和3个月测量的结果测量。在使用试验的第一部分数据确定能够将患者分为tPA组和安慰剂组的切点后，我们然后使用试验的第二部分数据来验证结果。结果：在tPA早期活动的5个最有效的结果测量中，有4个涉及美国国立卫生研究院卒中量表（NIHSS） 24小时评分或NIHSS评分从基线到24小时的变化。最佳的综合单一结局指标是24小时时NIHSS评分小于或等于2，其优势比为5.4 (95% CI， 2.4至12.1)，假设α值为0.05（双侧检验），使用第一部分数据的功率为80%，预计每个治疗组的样本量为58。在检测tPA长期疗效的前5个结果指标中，前2和前3也涉及NIHSS评分。3个月时的Rankin评分为0或1是第三个最有效的结果衡量指标。当应用于第n部分数据时，由CART从第1部分数据确定的结果测量在检测tPA有效性方面不那么敏感。结论：在NINDS tPA卒中试验中，与其他临床和放射学指标相比，使用NIHSS和Rankin评分小于或等于1的指标是tPA有效性的最敏感的鉴别指标。本探索性分析中确定的结局指标（例如，24小时时NIHSS评分小于或等于2）最好用于卒中发作后前3小时内开始的再通达的未来II期试验，其纳入和排除标准与NINDS tPA卒中试验相似。
Background and Purpose-We sought to identify the most powerful binary measures of the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) rTPA Stroke Trial,Methods-Using the Classification and Regression Tree (CART) algorithm, we evaluated binary cut points and combination of binary cut points with the 4 clinical scales and head CT imaging measures in the NINDS tPA Stroke Trial at 4 times after treatment: 2 hours, 24 hours, 7 to 10 days, and 3 months. The first analysis focused on detecting evidence of "early activity" of tPA with the use of outcome measures derived from the 2-hour and 24-hour clinical and radiographic measures, The second analysis focused on longer-term outcome and "efficacy" and used outcome measures derived from 7- to 10-day and 3-month measures. After identifying the cut points with the ability to classify patients into the tPA and placebo groups using part I data from the trial, we then used data from part II of the trial to validate the results.Results-Of the 5 most powerful outcome measures for early activity of tPA, 4 involved the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours or changes in the NIHSS score from baseline to 24 hours. The best overall single outcome measure was an NIHSS score less than or equal to 2 at 24 hours, which provided an odds ratio of 5.4 (95% CI, 2.4 to 12.1) and a projected sample size of 58 per treatment group assuming an alpha of 0.05 (2-sided test) and a power of 80% using part I data. The top 2 and 3 of the top 5 outcome measures for detecting the longer-term efficacy of tPA also involved the NIHSS score. A Rankin score of 0 or 1 at 3 months was the third most powerful outcome measure. Outcome measures identified by CART from part I data were not as sensitive in detecting the effectiveness of tPA when applied to part n data.Conclusions-Measures using the NIHSS and a Rankin score less than or equal to 1 were the most sensitive discriminators of the effectiveness of tPA in the NINDS tPA Stroke Trial compared with the other clinical and radiological measures. The outcome measures identified in this exploratory analysis (eg, NIHSS score less than or equal to 2 at 24 hours) would be best used as an outcome measure in future phase II trials of recanalization begun within the first 3 hours after stroke onset, with inclusion and exclusion criteria similar to those in the NINDS tPA Stroke Trial.