Hariri Geoffroy, Louie Jacqueline, Khan Aqsa, Tahir Peggy, Martin Guillaume L, Dechartres Agnès, Legrand Matthieu
Department of Anesthesia and Perioperative Care, Division of Critical Care Medicine, University of California, San Francisco, 521 Parnassus Ave, San Francisco, CA, 94143, USA.
Sorbonne Université, GRC 29, Groupe de Recherche Clinique en Anesthésie Réanimation médecine Périopératoire, ARPE, Paris, F-75012, France.
Crit Care. 2025 Jul 24;29(1):323. doi: 10.1186/s13054-025-05480-x.
In critical care randomized controlled trials (RCTs), obtaining informed consent from patients or proxies can be challenging and may delay randomization, potentially affecting intervention efficacy. Research without prior consent (RWPC) procedures are increasingly used to facilitate timely inclusion but their impact on trial outcomes remains uncertain. We aimed to assess whether RWPC procedures are associated with differences in intervention effects on mortality in critical care RCTs.
We searched PubMed and the Cochrane Database of Systematic Reviews from inception to August 1, 2024. We included meta-analyses of RCTs evaluating therapeutic interventions in critically ill adults, reporting mortality as a primary or secondary outcome. We conducted a meta-epidemiological study using a two-step approach. First, we calculated the ratio of odds ratios (ROR) within each meta-analysis to compare the effect of interventions on mortality between RCTs using RWPC and those using standard consent. Second, we pooled these RORs across meta-analyses using a random-effects model. Secondary outcomes included the delay from eligibility to randomization and the recruitment rate.
We included 42 meta-analyses comprising 323 RCTs and 103,011 patients, of which 59 RCTs (18%) used a RWPC procedure. Trials using RWPC were more recent (median year: 2015 [2008-2019] vs. 2012 [2007-2017]; p < 0.01), larger (sample size: 203 [101-605] vs. 72 [40-162]; p < 0.01), more frequently multicenter (80% vs. 43%; p < 0.01), and had lower overall risk of bias. There was no significant difference in intervention effect on mortality between trials with and without RWPC (pooled ROR, 1.05 [95% CI 0.83-1.34]; I²=71.7%). RWPC was associated with shorter time to randomization (3 [1-9] vs. 11 [4-23] hours; p < 0.01) and higher recruitment rates (9.6 [4.7-18.7] vs. 4.5 [1.9-8.6] patients/month; p = 0.01).
In critical care RCTs, RWPC procedures were not associated with differences in intervention effect on mortality but were linked to shorter time to randomization and higher recruitment rates.
在重症监护随机对照试验（RCT）中，从患者或代理人处获得知情同意可能具有挑战性，并且可能会延迟随机分组，这可能会影响干预效果。未经事先同意的研究（RWPC）程序越来越多地被用于促进及时纳入研究对象，但其对试验结果的影响仍不确定。我们旨在评估RWPC程序是否与重症监护RCT中干预措施对死亡率的影响差异相关。
我们检索了从数据库建立至2024年8月1日的PubMed和Cochrane系统评价数据库。我们纳入了对评估成年重症患者治疗性干预措施的RCT进行的荟萃分析，这些分析将死亡率作为主要或次要结局进行报告。我们采用两步法进行了一项荟萃流行病学研究。首先，我们计算每个荟萃分析中的比值比（OR）之比（ROR），以比较使用RWPC的RCT和使用标准同意程序的RCT中干预措施对死亡率的影响。其次，我们使用随机效应模型对这些荟萃分析中的ROR进行汇总。次要结局包括从符合纳入标准到随机分组的延迟时间和招募率。
我们纳入了42项荟萃分析，包括323项RCT和103,011名患者，其中59项RCT（18%）使用了RWPC程序。使用RWPC的试验更近（中位年份：2015年[2008 - 2019年] vs. 2012年[2007 - 2017年]；p < 0.01），规模更大（样本量：203[101 - 605] vs. 72[40 - 162]；p < 0.01），多中心试验更频繁（80% vs. 43%；p < 0.01），且总体偏倚风险更低。使用和未使用RWPC的试验在干预措施对死亡率的影响方面没有显著差异（汇总ROR，1.05[95%CI 0.83 - 1.34]；I² = 71.7%）。RWPC与更短的随机分组时间（3[1 - 9]小时 vs. 11[4 - 23]小时；p < 0.01）和更高的招募率相关（9.6[4.7 - 18.7]名患者/月 vs. 4.5[1.9 - 8.6]名患者/月；p = 0.01）。
在重症监护RCT中，RWPC程序与干预措施对死亡率的影响差异无关，但与更短的随机分组时间和更高的招募率相关。
