Department of Intensive Care, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Centre for Anaesthesiological Research, Department of Anaesthesiology, Zealand University Hospital, Køge, Denmark.
Crit Care Med. 2022 Oct 1;50(10):e759-e771. doi: 10.1097/CCM.0000000000005637. Epub 2022 Jul 27.
Randomized clinical trials (RCTs) conducted in adult ICU patients increasingly include patient-important outcomes other than mortality. This comes with challenges regarding outcome choices/definitions, handling of deceased patients and missing data in analyses, and choices of effect measures and statistical methods due to complex distributions. This scoping review aimed to characterize how these challenges are handled in relevant contemporary RCTs.
We systematically searched 10 selected journals for RCTs conducted primarily in adult ICU patients published between 1 January 2018 and 5 May 2022 reporting at least one patient-important outcome other than mortality, including "days alive without"…-type outcomes, functional/cognitive/neurologic outcomes, health-related quality of life (HRQoL) outcomes, and ordinal/other outcomes.
Abstracts and full-texts were assessed independently and in duplicate by two reviewers.
Data were extracted independently and in duplicate by two reviewers using predefined and pilot-tested extraction forms and subsequently categorized to facilitate analysis.
We included 687 outcomes from 167 RCTs, with 32% of RCTs using a patient-important outcome other than mortality as a (co-)primary outcome, most frequently "days alive without"…-type outcomes. Many different functional/cognitive/neurologic (103) and HRQoL (29) outcomes were reported. Handling of deceased patients varied, with analyses frequently restricted to survivors only for functional/cognitive/neurologic (62%) and HRQoL (89%) outcomes. Follow-up was generally longer and missing data proportions higher for functional/cognitive/neurologic and HRQoL outcomes. Most outcomes were analyzed using nonparametric tests (31%), linear regression/ t tests (27%), chi-square-like tests (12%), and proportional odds logistic regression (9%), often without presentation of actual treatment effects estimates (38%).
In this sample of RCTs, substantial variation in practice and suboptimal methodological choices were observed. This calls for increased focus on standardizing outcome choices and definitions, adequate handling of missing data and deceased patients in analyses, and use of statistical methods quantifying effect sizes.
越来越多的成人 ICU 患者随机临床试验（RCT）纳入了除死亡率以外的患者重要结局。这带来了一些挑战，包括结局选择/定义、分析中处理死亡患者和缺失数据的方法，以及由于复杂分布而选择效应测量和统计方法。本范围综述旨在描述这些挑战在相关当代 RCT 中是如何处理的。
我们系统地在 10 种选定的期刊中搜索了 2018 年 1 月 1 日至 2022 年 5 月 5 日期间发表的主要在成人 ICU 患者中进行的 RCT，这些 RCT 报告了除死亡率以外的至少一种患者重要结局，包括“无……天存活”……型结局、功能/认知/神经结局、健康相关生活质量（HRQoL）结局以及序贯/其他结局。
两名评审员分别独立评估摘要和全文。
两名评审员使用预定义和经过试点测试的提取表格独立提取数据，然后对数据进行分类，以便于分析。
我们纳入了 167 项 RCT 的 687 项结局，其中 32%的 RCT 将患者重要结局以外的死亡率作为（共同）主要结局，最常见的是“无……天存活”……型结局。报告了许多不同的功能/认知/神经（103）和 HRQoL（29）结局。处理死亡患者的方法各不相同，分析通常仅限于幸存者，仅用于功能/认知/神经（62%）和 HRQoL（89%）结局。功能/认知/神经和 HRQoL 结局的随访时间通常更长，缺失数据比例更高。大多数结局使用非参数检验（31%）、线性回归/ t 检验（27%）、类似卡方检验（12%）和比例优势逻辑回归（9%）进行分析，而没有报告实际治疗效果估计值（38%）。
在本 RCT 样本中，观察到实践中的大量差异和不理想的方法选择。这需要更加关注标准化结局选择和定义、分析中缺失数据和死亡患者的处理以及量化效应大小的统计方法的使用。
