Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials.
Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials.
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DOI：
10.1161/strokeaha.117.017866
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发表时间：
2017-07
期刊：
影响因子：
8.3
通讯作者：
Elm J
中科院分区：
文献类型：
--
作者：
Broderick JP;Adeoye O;Elm J
2017年7月2008年卒中mRS部分取决于是否满足比例优势假设。16，18经过该领域的科学讨论和辩论，研究人员设计了FDA批准的试验，使用mRS的有序分布作为主要结局指标。20，21尽管尚未显示所有可能检验的相对有效性，但当治疗获益在mRS的多个水平相似发生时，使用mRS的整个分布可能比二分分析具有更大的统计功效，而不是仅在一端聚类，22尽管应进行模拟以确认任何给定假设治疗效应的这一点。有序方法的一个缺点是传达有序尺度上分布的变化对患者和医生意味着什么。此外，入组受试者的严重程度分布可能影响有序方法捕获健康状态转换的能力。最近，焦点一直是以患者为中心的结果或生活质量，最广泛接受的以患者为中心的结果测量是效用-患者对特定健康结果的期望。[23]效用值为1表示非常健康。STAIR（卒中治疗学术行业圆桌会议）建议开发mRS的效用加权（UW）版本。24研究者随后通过将EQ-5D（欧洲生活质量量表）25的反应映射到卒中患者人群的mRS水平，计算了不同水平mRS的效用值。22，26，27在另一项研究中，使用WHOGBD（世界卫生组织全球疾病负担项目）的方法得出mRS水平的残疾权重。28在这些方法的基础上，完成了UW-mRS（表2），并与之前8项急性卒中试验中的顺序和二分方法进行了比较。22，27，28该分析证明了UW-mRS和有序mRS与二分分析相比的潜在优势。UW-mRS的分析在计算上是简单的，使用t检验比较治疗组之间的平均效用差异，并且UW-mRS可以很容易地扩展到纳入基线协变量的调整。效用指标（如UW-mRS）的另一个特征是能够生成通过干预或治疗获得或损失的质量调整生命年（QUID）。29-33一个QALY指标假设一年的生活在完美的健康是值得1 QALY（1年的生活× 1效用值= 1 QALY），而一年的生活在低于这个完美的健康状态是值得不到一个。为了确定准确的QALY值，将与给定健康状态相关的效用值乘以在该状态下生活的年数。例如，1年的完全健康生活或2年的完全健康生活值的一半，由患者判断都相当于1 QALY。为了说明QRR的计算方法，我们使用一个简化的假设示例，即急性卒中试验（1000例卒中前健康状况良好的受试者）（mRS为0，UW-mRS效用为1）和NINDS tPA试验中观察到的mRS分布。在NINDS tPA试验中，通过UW-mRS测量的静脉tPA与安慰剂相比，90天时的效应量为0.09（来自DAWN [DWI或CTP评估，在接受神经干预的清醒和迟发性卒中的分类中存在临床不匹配]试验22的UW-mRS方法，如表2所示）。QALY计算为0.09效用差异× 0.25年= 0.0225 QALY S（或8.2生活质量日/年）。
2008 Stroke July 2017 mRS that depend, in part, on meeting or not meeting the proportional odds assumption. 16, 18 After scientific discussion and debate in the field, investigators designed FDA-approved trials that use the ordinal distribution of the mRS as the primary outcome measure. 20, 21 Although the relative efficiency has not been shown for all possible tests, using the entire distribution of the mRS may have greater statistical power than a dichotomized analyses when the treatment benefit occurs similarly at several levels of the mRS, rather than clustering at just one end, 22 although simulations should be conducted to confirm this for any given hypothesized treatment effect. One disadvantage of the ordinal approach is communicating what a change across the distribution on an ordinal scale means to patients and physicians. Furthermore, the severity distribution of enrolled subjects may affect the ability of the ordinal approach to capture transitions across health states. More recently, the focus has been on patient-centered outcomes or quality of life, and the most widely accepted patientcentered outcome measure is utility—the desirability of a specific health outcome to the patient. 23 A utility of 1 represents excellent health. The STAIR (Stroke Therapy Academic Industry Roundtable) recommended the development of a utility-weighted (UW) version of the mRS. 24 Investigators subsequently calculated utility values for the various levels of the mRS by mapping responses from the EQ-5D (European Quality of Life Scale) 25 onto the mRS levels in populations of patients with stroke. 22, 26, 27 In another study, disability weights for mRS levels were derived using the methodology of the WHOGBD (World Health Organization Global Burden of Disease Project). 28 On the basis of these approaches, a UW-mRS was accomplished (Table 2) and compared with ordinal and dichotomous approaches in 8 previous acute stroke trials. 22, 27, 28 This analysis demonstrated the potential advantages of both theUW-mRS and the ordinal mRS when compared with the dichotomous analyses. Analysis of the UW-mRS is computationally straightforward, using t tests that compare the mean utility difference between treatment arms, and the UW-mRS can easily be extended to incorporate adjustments of baseline covariates. An additional feature of a utility measure such as the UW-mRS is the ability to generate quality-adjusted-life-years (QALYs) gained or lost by an intervention or treatment. 29–33 A QALY measure assumes that a year of life lived in perfect health is worth 1 QALY (1 year of life× 1 utility value= 1 QALY) and that a year of life lived in a state of less than this perfect health is worth less than one. To determine the exact QALY value, one multiplies the utility value associated with a given state of health by the years lived in that state. For example, 1 year lived with perfect health or 2 years lived at half of the value of perfect health as judged by patients are both equivalent to 1 QALY. To illustrate how QALYs are calculated, let us use a simplified hypothetical example of an acute stroke trial of 1000 subjects in excellent health before the stroke (mRS of 0 and UW-mRS utility of 1) and the mRS distributions observed in the NINDS tPA trials. The effect size at 90 days for intravenous tPA versus placebo in the NINDS tPA trials as measured by the UW-mRS is 0.09 (UW-mRS methodology from the DAWN [DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention] trial22 as shown in Table 2). The QALY calculation is 0.09 utility difference× 0.25 years= 0.0225 QALYS (or 8.2 quality-of-life days per …