Published in:
Open Access 01-12-2018 | Research
Sample size implications of mortality definitions in sepsis: a retrospective cohort study
Published in: Trials | Issue 1/2018
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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.