Impact of weighted composite compared to traditional composite endpoints for the design of randomized controlled trials
Impact of weighted composite compared to traditional composite endpoints for the design of randomized controlled trials
复制标题
DOI：
10.1177/0962280211436004
复制
发表时间：
2015-12-01
影响因子：
2.3
通讯作者：
Armstrong, Paul W.
中科院分区：
文献类型：
--
作者：
Bakal, Jeffrey A.;Westerhout, Cynthia M.;Armstrong, Paul W.
复合终点常用于心血管临床试验。当使用复合端点时，当第一个组件端点发生时，主体被认为发生了事件。复合终点的使用提供了合并多个临床重要终点事件的能力，从而提高了事件发生率并提高了给定样本量的统计功效。组合的一个假设是所有组成事件都具有同等的临床重要性。鉴于所包含的组件端点的多样性，这种假设很少实现。调整这种多样性的一种方法是使用先验确定的严重性权重来调整结果。使用加权终点还允许为每个患者合并多个终点。尽管对结果进行加权会降低事件的有效数量，但它提供了减少估计方差的附加信息。我们创建了一系列模拟研究，以检查典型复合材料的各个组件发生变化时对功率的影响。在一项研究中，我们注意到，当组成部分结果改变时，加权综合方法能够提供区分能力，而传统方法则不能。在另一项研究中，我们注意到，当变化是由更严重的终点驱动时，加权复合材料提供了与传统复合材料相似的功效水平。
Composite endpoints are commonly used in cardiovascular clinical trials. When using a composite endpoint a subject is considered to have an event when the first component endpoint has occurred. The use of composite endpoints offers the ability to incorporate several clinically important endpoint events thereby augmenting the event rate and increasing statistical power for a given sample size. One assumption of the composite is that all component events are of equal clinical importance. This assumption is rarely achieved given the diversity of component endpoints included. One means of adjusting for this diversity is to adjust the outcomes using severity weights determined a priori. The use of a weighted endpoint also allows for the incorporation of multiple endpoints per patient. Although weighting the outcomes lowers the effective number of events, it offers additional information that reduces the variance of the estimate. We created a series of simulation studies to examine the effect on power as the individual components of a typical composite were changed. In one study, we noted that the weighted composite was able to offer discriminative power when the component outcomes were altered, while the traditional method was not. In the other study, we noted that the weighted composite offered a similar level of power to the traditional composite when the change was driven by the more severe endpoints.