Silva José Mário Nunes da, Conceição Juliana Ferreira Souza, Ramírez Paula Camila, Diaz-León Christian Leonardo, Diaz-Quijano Fredi Alexander
Universidade de São Paulo, School of Public Health, Graduate Program in Epidemiology - São Paulo (SP), Brazil.
Universidade de São Paulo, School of Public Health - São Paulo (SP), Brazil.
Rev Bras Epidemiol. 2025 Jun 27;28:e250035. doi: 10.1590/1980-549720250035. eCollection 2025.
The aim of this study was to investigate the prevalence of bias attributable to composite outcome (BACO) in clinical trials.
We searched PubMed for randomized clinical trials where the primary outcome was a binary composite that included all-cause mortality among its components from January 1, 2019, to December 31, 2020. For each trial, the BACO index was calculated to assess the correspondence between effects on the composite outcome and mortality. This systematic review was registered in PROSPERO (CRD42021229554).
After screening 1,076 citations and 171 full-text articles, 91 studies were included from 13 different medical areas. The prevalence of significant or suggestive BACO among the 91 included articles was 25.2% (n=23), including 12 with p<0.005 and 11 with p between 0.005 and <0.05. We observed that in 17 (73.9%) of these 23 studies, the BACO index value was between 0 and <1, indicating an underestimation of the effect. The other six studies showed negative values (26.1%), indicating an inversion of the association with mortality. None of the studies showed significant overestimation of the association attributable to the composite outcome.
These findings highlight the need to predefine guidelines for interpreting effects on composite endpoints based on objective criteria such as the BACO index.
本研究旨在调查临床试验中复合结局所致偏倚（BACO）的发生率。
我们在PubMed中检索了2019年1月1日至2020年12月31日期间以二元复合结局为主要结局且其组成部分包括全因死亡率的随机临床试验。对于每项试验，计算BACO指数以评估对复合结局的效应与死亡率之间的对应关系。该系统评价已在PROSPERO（CRD42021229554）中注册。
在筛选了1076篇引文和171篇全文文章后，纳入了来自13个不同医学领域的91项研究。在纳入的91篇文章中，显著或提示性BACO的发生率为25.2%（n = 23），其中12篇p<0.005，11篇p在0.005至<0.05之间。我们观察到，在这23项研究中的17项（73.9%）中，BACO指数值在0至<1之间，表明效应被低估。其他6项研究显示为负值（26.1%），表明与死亡率的关联发生了反转。没有研究显示因复合结局导致的关联被显著高估。
这些发现凸显了需要基于诸如BACO指数等客观标准预先制定解释对复合终点效应的指南。
