Office of Biostatistics Research, Division of Intramural Research of the National Heart, Lung, and Blood Institute, NIH/DHHS, Bethesda, Maryland, USA.
Inova Heart and Vascular Institute, Fairfax, Virginia, USA.
Stat Med. 2024 May 10;43(10):1920-1932. doi: 10.1002/sim.10045. Epub 2024 Feb 28.
Consider the choice of outcome for overall treatment benefit in a clinical trial which measures the first time to each of several clinical events. We describe several new variants of the win ratio that incorporate the time spent in each clinical state over the common follow-up, where clinical state means the worst clinical event that has occurred by that time. One version allows restriction so that death during follow-up is most important, while time spent in other clinical states is still accounted for. Three other variants are described; one is based on the average pairwise win time, one creates a continuous outcome for each participant based on expected win times against a reference distribution and another that uses the estimated distributions of clinical state to compare the treatment arms. Finally, a combination testing approach is described to give robust power for detecting treatment benefit across a broad range of alternatives. These new methods are designed to be closer to the overall treatment benefit/harm from a patient's perspective, compared to the ordinary win ratio. The new methods are compared to the composite event approach and the ordinary win ratio. Simulations show that when overall treatment benefit on death is substantial, the variants based on either the participants' expected win times (EWTs) against a reference distribution or estimated clinical state distributions have substantially higher power than either the pairwise comparison or composite event methods. The methods are illustrated by re-analysis of the trial heart failure: a controlled trial investigating outcomes of exercise training.
考虑临床试验中整体治疗效果的结果选择，该试验衡量了几种临床事件的首次发生时间。我们描述了几种新的赢率变体，这些变体将共同随访期间的每个临床状态所花费的时间纳入其中，其中临床状态是指到那时发生的最严重的临床事件。有一种变体允许限制，以便随访期间的死亡是最重要的，而同时仍要考虑其他临床状态所花费的时间。还描述了另外三种变体；一种基于平均成对赢时间，一种为每个参与者创建基于预期赢时间与参考分布的连续结果，另一种则使用临床状态的估计分布来比较治疗臂。最后，描述了一种组合检验方法，以在广泛的替代方案中提供稳健的检测治疗效果的功效。与普通赢率相比，这些新方法旨在更接近患者角度的整体治疗效果/危害。将新方法与复合事件方法和普通赢率进行了比较。模拟结果表明，当死亡的整体治疗效果显著时，基于参与者与参考分布的预期赢时间（EWT）或估计的临床状态分布的变体比两两比较或复合事件方法具有更高的功效。通过对心力衰竭试验的重新分析说明了这些方法：一项控制试验，调查运动训练的结果。
