School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia.
School of Pharmacy, Monash University, Subang Jaya, Malaysia.
Neonatology. 2021;118(3):259-263. doi: 10.1159/000514402. Epub 2021 Mar 29.
Composite outcomes are used to increase the power of a study by combining event rates. Many composite outcomes in adult clinical trials have components that differ substantially in patient importance, event rate, and effect size, making interpretation challenging. Little is known about the use of composite outcomes in neonatal randomized controlled trials (RCTs).
We assessed the use of composite outcomes in neonatal RCTs included in Cochrane Neonatal reviews published till November 2017. Two authors reviewed the components of the composite outcomes to compare their patient importance and computed the ratios of effect sizes and event rates between the components, with an a priori threshold of 1.5, indicating a substantial difference. Descriptive statistics were presented.
We extracted 7,766 outcomes in 2,134 RCTs in 312 systematic reviews. Among them, 55 composite outcomes (0.7%) were identified in 46 RCTs. The vast majority (92.7%) of composite outcomes had 2 components, with death being the most common component (included 51 times [92.7%]). The components in nearly three-quarters of the composite outcomes (n = 40 [72.7%]) had different patient importance, while the effect sizes and event rates differed substantially between the components in 27 (49.1%) and 35 (63.6%) outcomes, respectively, with up to 43-fold difference in the event rates observed.
The majority of composite outcomes in neonatal RCTs had different patient importance with contrasting effect sizes and event rates between the components. In patient communication, clinicians should highlight individual components, rather than the composites, with explanation on the relationship between the components, to avoid misleading impression on the effect of the intervention. Future trials should report the estimates of all individual components alongside the composite outcomes presented.
复合结局用于通过组合事件率来提高研究的效力。许多成人临床试验中的复合结局在患者重要性、事件率和效应大小方面有很大的不同，这使得解释变得具有挑战性。在新生儿随机对照试验（RCT）中使用复合结局的情况知之甚少。
我们评估了截止到 2017 年 11 月发表的 Cochrane 新生儿综述中包含的新生儿 RCT 中复合结局的使用情况。两名作者对复合结局的组成部分进行了回顾，比较了它们在患者重要性方面的差异，并计算了组成部分之间的效应大小和事件率比值，预先设定阈值为 1.5，表示存在显著差异。描述性统计数据。
我们从 312 项系统综述中的 2134 项 RCT 中提取了 7766 项结局。其中，在 46 项 RCT 中发现了 55 个复合结局（0.7%）。绝大多数（92.7%）复合结局有 2 个组成部分，死亡是最常见的组成部分（出现 51 次[92.7%]）。近四分之三（72.7%）的复合结局的组成部分在患者重要性方面存在差异，而在 27 项（49.1%）和 35 项（63.6%）结局中，组成部分之间的效应大小和事件率差异显著，事件率差异最大可达 43 倍。
新生儿 RCT 中大多数复合结局的组成部分在患者重要性方面存在差异，且组成部分之间的效应大小和事件率存在显著差异。在与患者沟通时，临床医生应强调各组成部分，而不是复合结局，并解释各组成部分之间的关系，以避免对干预效果产生误导性印象。未来的试验应报告所有单独组成部分的估计值，以及呈现的复合结局。
