Marmiere Marilena, D'Amico Filippo, Monti Giacomo, Landoni Giovanni
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Crit Care Med. 2025 May 1;53(5):e1116-e1124. doi: 10.1097/CCM.0000000000006532. Epub 2024 Dec 4.
The Sequential Organ Failure Assessment (SOFA) score originated as a tool for assessing organ dysfunction in critical illness but has expanded to become an outcome measure in clinical trials. We aimed to assess how the SOFA score was used as the primary or secondary endpoint of major randomized controlled trials (RCTs).
Independent reviewers searched MEDLINE/PubMed, Scopus, and Embase databases.
Articles were selected when they fulfilled: 1) RCT; 2) SOFA score was primary or secondary endpoint; and 3) published in the Lancet , New England Journal of Medicine , or Journal of the American Medical Association .
Data collection included study details, outcomes, statistical differences in SOFA score, choice of score statistics, timepoints of SOFA reporting, and how missing data and competing risks analysis were managed.
Twenty-three RCTs had SOFA score as outcome measure, eight used it as primary endpoint. Daily maximum SOFA was the key statistic in 11 RCTs, delta SOFA was used in eight, and mean SOFA in four. Mean SOFA was most frequently chosen as primary endpoint (4/8, 50%). There were 18 different outcome assessment timepoints, ranging from 1 to 28 days. Three RCTs reported statistically significant difference in SOFA between groups. Handling of missing SOFA scores was not described in ten of 23 RCTs. When described, it varied from study to study with variable imputation methods and variable accounting for the competing risk of mortality and ICU discharge.
There is major variability in the choice of summary statistic for SOFA score analysis and assessment timepoints, when using it as outcome measure in RCTs. There was either no information or great variability in the handling of missing values, use of imputation, and accounting for competing risk. The current use of SOFA scores in RCTs lacks sufficient reproducibility and statistical and methodological robustness.
序贯器官衰竭评估（SOFA）评分最初是作为评估危重病患者器官功能障碍的工具，但已扩展成为临床试验中的一项结局指标。我们旨在评估SOFA评分如何被用作主要随机对照试验（RCT）的主要或次要终点。
独立评审员检索了MEDLINE/PubMed、Scopus和Embase数据库。
符合以下条件的文章被选中：1）RCT；2）SOFA评分是主要或次要终点；3）发表于《柳叶刀》《新英格兰医学杂志》或《美国医学会杂志》。
数据收集包括研究细节、结局、SOFA评分的统计学差异、评分统计方法的选择、SOFA报告的时间点，以及如何处理缺失数据和竞争风险分析。
23项RCT将SOFA评分作为结局指标，其中8项将其用作主要终点。每日最高SOFA是11项RCT中的关键统计指标，8项使用SOFA变化值，4项使用平均SOFA。平均SOFA最常被选为主要终点（4/8，50%）。有18个不同的结局评估时间点，从1天到28天不等。3项RCT报告了组间SOFA存在统计学显著差异。23项RCT中有10项未描述对缺失SOFA评分的处理。在进行描述时，不同研究之间存在差异，包括不同的插补方法以及对死亡和重症监护病房出院竞争风险的不同处理方式。
在RCT中将SOFA评分用作结局指标时，用于SOFA评分分析的汇总统计量选择和评估时间点存在很大差异。在缺失值处理、插补方法的使用以及竞争风险的处理方面，要么没有信息，要么存在很大差异。目前RCT中SOFA评分的使用缺乏足够的可重复性以及统计和方法学稳健性。
