Randomised clinical trials (RCTs) are the gold standard for providing unbiased evidence of intervention effects. Here, we provide an overview of the history of RCTs and discuss the major challenges and limitations of current critical care RCTs, including overly optimistic effect sizes; unnuanced conclusions based on dichotomization of results; limited focus on patient-centred outcomes other than mortality; lack of flexibility and ability to adapt, increasing the risk of inconclusive results and limiting knowledge gains before trial completion; and inefficiency due to lack of re-use of trial infrastructure. We discuss recent developments in critical care RCTs and novel methods that may provide solutions to some of these challenges, including a research programme approach (consecutive, complementary studies of multiple types rather than individual, independent studies), and novel design and analysis methods. These include standardization of trial protocols; alternative outcome choices and use of core outcome sets; increased acceptance of uncertainty, probabilistic interpretations and use of Bayesian statistics; novel approaches to assessing heterogeneity of treatment effects; adaptation and platform trials; and increased integration between clinical trials and clinical practice. We outline the advantages and discuss the potential methodological and practical disadvantages with these approaches. With this review, we aim to inform clinicians and researchers about conventional and novel RCTs, including the rationale for choosing one or the other methodological approach based on a thorough discussion of pros and cons. Importantly, the most central feature remains the randomisation, which provides unparalleled restriction of confounding compared to non-randomised designs by reducing confounding to chance.

随机临床试验 (RCT) 是提供干预效果的公正证据的金标准。在这里，我们概述了 RCT 的历史，并讨论了当前重症监护 RCT 的主要挑战和局限性，包括过于乐观的效应量；基于结果二分法的不细致的结论；对死亡率以外的以患者为中心的结果的关注有限；缺乏灵活性和适应能力，增加了不确定结果的风险并限制了试验完成前的知识获取；由于缺乏对试验基础设施的重用，效率低下。我们讨论了重症监护 RCT 的最新发展和可能为其中一些挑战提供解决方案的新方法，包括研究计划方法（多种类型而非个体的连续、互补研究，独立研究），以及新颖的设计和分析方法。其中包括试验方案的标准化；替代结果选择和核心结果集的使用；增加对不确定性、概率解释和贝叶斯统计使用的接受度；评估治疗效果异质性的新方法；适配和平台试验；并增加临床试验和临床实践之间的整合。我们概述了这些方法的优点并讨论了这些方法的潜在方法和实际缺点。通过这篇综述，我们旨在让临床医生和研究人员了解传统和新型 RCT，包括基于对利弊的全面讨论选择一种或另一种方法的基本原理。重要的是，最核心的特征仍然是随机化，