OBJECTIVES: 

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.

DATA SOURCES: 

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.

STUDY SELECTION: 

Abstracts and full-texts were assessed independently and in duplicate by two reviewers.

DATA EXTRACTION: 

Data were extracted independently and in duplicate by two reviewers using predefined and pilot-tested extraction forms and subsequently categorized to facilitate analysis.

DATA SYNTHESIS: 

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%).

CONCLUSIONS: 

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.

中文翻译：

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当代 ICU 试验中除死亡率以外对患者重要的结果：范围界定审查

目标： 

在成人 ICU 患者中进行的随机临床试验 (RCT) 越来越多地包括除死亡率以外的患者重要结局。这带来了以下方面的挑战：结果选择/定义、已故患者的处理和分析中缺失的数据，以及由于复杂的分布而导致的效果测量和统计方法的选择。本次范围界定审查旨在描述相关当代随机对照试验如何应对这些挑战。

数据源： 

我们系统地检索了 10 种精选期刊，主要针对 ICU 成年患者，发表时间为 2018 年 1 月 1 日至 2022 年 5 月 5 日，报告至少一项除死亡率以外的患者重要结局，包括“没有生存的日子”……类型的结局、功能/认知/神经系统结果、健康相关生活质量 (HRQoL) 结果以及序数/其他结果。

研究选择： 

摘要和全文由两名审稿人独立评估，一式两份。

数据提取： 

两名评审员使用预定义和试点测试的提取表格独立且重复地提取数据，并随后进行分类以方便分析。

数据综合： 

我们纳入了 167 项随机对照试验中的 687 项结果，其中 32% 的随机对照试验使用死亡率以外的患者重要结果作为（共同）主要结果，最常见的是“没有生存的日子”……类型的结果。报告了许多不同的功能/认知/神经学 (103) 和 HRQoL (29) 结果。对已故患者的处理各不相同，分析通常仅限于幸存者，仅针对功能/认知/神经系统 (62%) 和 HRQoL (89%) 结果。功能/认知/神经系统和 HRQoL 结果的随访时间通常较长，缺失数据比例较高。大多数结果是使用非参数检验（31％）、线性回归/ t检验（27％）、卡方检验（12％）和比例优势逻辑回归（9％）进行分析，通常没有呈现实际的治疗效果估计（38%）。

结论： 

在这个随机对照试验样本中，观察到实践的巨大差异和次优的方法选择。这要求更多地关注标准化结果选择和定义，在分析中充分处理缺失数据和已故患者，以及使用量化效应大小的统计方法。