What areas should research in sepsis focus on?

Key Research Priorities for Sepsis

Research in sepsis should focus on creating large richly phenotyped harmonized knowledge networks of clinical, imaging, and multianalyte molecular data to advance precision medicine approaches that can reduce morbidity and mortality. 1

Priority Research Areas in Sepsis

1. Knowledge Networks and Data Integration

• Create comprehensive, harmonized knowledge networks that integrate clinical, imaging, and molecular data from sepsis patients 1
• Include biospecimen collection (before randomization and longitudinally) in observational studies and RCTs 1
• Modify consent processes to ensure data and biological samples can be widely shared with investigators for collaborative efforts 1

2. Novel Trial Designs

• Implement adaptive platform trial designs to identify precision medicine strategies 1
• Move beyond traditional RCTs to designs that can identify heterogeneity of treatment effect (HTE) 1
• Develop trials that can validate subgroups likely to benefit from specific interventions 1

3. Advanced Data Science and Engineering

• Develop methods to identify responsive patient subgroups using combinations of clinical and molecular markers across multiple omics platforms 1
• Create approaches to modify treatments in response to rapid changes in host immune response 1
• Advance causal modeling techniques when RCT data are sparse 1

4. Real-Time Application Tools

• Develop tools for real-time application of precision medicine in ICU settings 1
• Integrate electronic health records with decision support systems 1
• Create rapid diagnostic and prognostic tools that can be implemented at the bedside 1

5. Inclusive Research Approaches

• Ensure precision medicine strategies are applicable across diverse racial, ethnic, socioeconomic, and demographic groups 1
• Address barriers to implementation in resource-limited settings 2
• Develop context-specific approaches recognizing differences in at-risk populations and infecting pathogens 2

6. Complexity Science Integration

• Apply complexity theory to understand sepsis as a highly complex, non-linear system 3
• Focus on longitudinal, continuous biological data collection 3
• Integrate computational modeling with biological data to identify key pathways for intervention 3

Implementation Challenges and Solutions

Current Limitations

• Fragmented knowledge networks with limited integration across institutions 1
• Insufficient biospecimen collection in many trials 1
• Limited application of novel trial designs in sepsis research 1

Practical Solutions

• Establish collaborative international research networks 1
• Secure sustainable funding mechanisms for precision medicine efforts 1
• Develop standardized protocols for biospecimen collection and data sharing 1
• Create research infrastructure that spans resource-rich and resource-limited settings 2

Pitfalls to Avoid

• Focusing solely on single biomarkers rather than integrated multi-omics approaches
• Neglecting the dynamic nature of sepsis by collecting only static measurements
• Failing to account for heterogeneity in sepsis populations when designing trials
• Overlooking implementation challenges in resource-limited settings where sepsis burden is highest 2
• Applying one-size-fits-all approaches instead of context-specific solutions 2

By prioritizing these research areas, the field can advance toward precision medicine approaches that recognize the complexity of sepsis and develop targeted interventions to improve outcomes across diverse patient populations and healthcare settings.