Mortality time frame variability in septic shock clinical trials: A systematic review.

Summary

Across 132 septic shock RCTs, mortality endpoints were highly heterogeneous with 15 unique time frames; 28-day mortality was most common (74%), but hospital, ICU, and 90-day mortality were also frequently used. Such variability risks biased effect estimates and complicates meta-analyses, calling for consensus on standardized mortality time frames.

Key Findings

• Among 132 septic shock RCTs, 234 mortality endpoints included 15 unique time frames.
• 28-day mortality was most frequently reported (74%), followed by hospital, ICU, and 90-day mortality.
• Temporal/geographic patterns exist; combined hospital+ICU mortality reporting decreased from 2008–2013 to 2014–2019 (P=0.043).

Clinical Implications

Standardizing mortality time frames (e.g., 28 and 90 days) would improve comparability of septic shock trials, support guideline development, and enhance meta-analytic power.

Limitations

• No meta-analysis; potential selection bias from reported endpoints.
• Does not test how differing endpoints alter treatment effect estimates within specific trials.

Future Directions

Develop and adopt consensus core outcome sets (e.g., 28- and 90-day mortality) and harmonized statistical plans to enable robust comparisons and meta-analyses.