脓毒症中死亡率定义对样本量的影响：一项回顾性队列研究。

Sample size implications of mortality definitions in sepsis: a retrospective cohort study.

作者信息

Govindan Sushant, Prescott Hallie C, Chopra Vineet, Iwashyna Theodore J

机构信息

Department of Medicine, University of Michigan Health System, Ann Arbor, MI, USA.

Patient Safety Enhancement Program, Ann Arbor VA Healthcare System, Ann Arbor, MI, USA.

出版信息

Trials. 2018 Mar 27;19(1):198. doi: 10.1186/s13063-018-2570-2.

DOI:10.1186/s13063-018-2570-2

PMID:29587803

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5870299/

Abstract

BACKGROUND

Many randomized controlled trials (RCTs) employ mortality at a given time as a primary outcome. There are at least three common ways to measure 90-day mortality: first, all-location mortality, that is, all-cause mortality within 90 days of randomization at any location. Second, ARDSnet mortality is death in a healthcare facility of greater intensity than the patient was in prior to the hospitalization during which they were randomized. Finally, in-hospital mortality is death prior to discharge from the primary hospitalization of randomization. Data comparing the impact of these different measurements on sample size are lacking. We evaluated the extent to which event rates vary by mortality definition.

METHODS

This was a retrospective cohort study of 30,691 patients hospitalized at Veterans Affairs (VA) hospitals for sepsis during 2009. 12,727 (41.5%) received care in an ICU setting. For each patient, we measured event rates for three different 90-day mortality outcomes: all-location mortality, ARDSnet mortality, and in-hospital mortality. We also calculated sample sizes necessary to power an example RCT given those event rates.

RESULTS

At 90 days, all-location mortality was 26.4% (95% CI 25.9-26.9%), ARDSnet mortality was 19.2% (95% CI 18.8-19.7%), and in-hospital mortality was 13.4% (95% CI 13.0-13.8%) (p < 0.01 all comparisons). These respective event rates result in different required sample sizes to achieve a 20% relative reduction in mortality with 80% power and a 5% false positive rate. Such a trial of VA sepsis patients would require 2080 patients for all-location mortality, 3080 for ARDSnet mortality, and 4796 for in-hospital mortality. Among sepsis patients mechanically ventilated in an ICU, 2438 experienced all-location mortality (46.2% [95% CI 44.8-47.5%]), 2181 experienced ARDSnet mortality (41.3% [95% CI 40.0-42.6%]), and 1894 experienced in-hospital mortality (36.0% [95% CI 34.7-37.3%]).

CONCLUSIONS

Event rates vary substantially in sepsis patients based on the chosen 90-day mortality definition. This could have important implications for RCT design trade-offs.

摘要

背景

许多随机对照试验（RCT）将特定时间的死亡率作为主要结局。测量90天死亡率至少有三种常见方法：第一，全地点死亡率，即随机分组后90天内在任何地点的全因死亡率。第二，急性呼吸窘迫综合征网络（ARDSnet）死亡率，是指在比患者随机分组前住院时更高强度的医疗机构中死亡。最后，住院死亡率是指在随机分组后的首次住院期间出院前死亡。缺乏比较这些不同测量方法对样本量影响的数据。我们评估了事件发生率因死亡率定义而异的程度。

方法

这是一项对2009年在退伍军人事务部（VA）医院因脓毒症住院的30691例患者进行的回顾性队列研究。12727例（41.5%）在重症监护病房（ICU）接受治疗。对于每例患者，我们测量了三种不同的90天死亡率结局的事件发生率：全地点死亡率、ARDSnet死亡率和住院死亡率。我们还计算了在这些事件发生率下为一个示例RCT提供足够检验效能所需的样本量。

结果

在90天时，全地点死亡率为26.4%（95%置信区间25.9 - 26.9%），ARDSnet死亡率为19.2%（95%置信区间18.8 - 19.7%），住院死亡率为13.4%（95%置信区间13.0 - 13.8%）（所有比较p < 0.01）。这些各自的事件发生率导致为实现死亡率相对降低20%、检验效能为80%和假阳性率为5%所需的不同样本量。这样一项针对VA脓毒症患者的试验，全地点死亡率需要2080例患者，ARDSnet死亡率需要3080例，住院死亡率需要4796例。在ICU接受机械通气的脓毒症患者中，2438例发生全地点死亡（46.2% [95%置信区间44.8 - 47.5%]），2181例发生ARDSnet死亡（41.3% [95%置信区间40.0 - 42.6%]），1894例发生住院死亡（36.0% [95%置信区间34.7 - 37.3%]）。