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Table 1 Potential factors contributing to the lack of “bench-to-bedside” translational success of preclinical sepsis research

From: National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research

Domain Preclinical model Human condition
Construct validity
 Patient population Historically male, however more female animals in recent years
Healthy
Young/juvenile
Limited environmental exposure
Genetically homogeneous
Female and male
Medical comorbidities
Old and young
Environmental stressors
Genetically diverse
 Site of infection Non-bacterial surrogates (e.g. endotoxin)
Polymicrobial abdominal/enteric Gram-negative
Pneumonia (rare)
Fungi/protozoa (rare)
Virus (very rare)
Soft tissue Gram-positive
Abdominal Gram-negative, including biliary
Pneumonia (common)
Virus (common)
Fungi/protozoa
 Intercurrent therapy None
Antibiotics (monotherapy)
Fluids
Anesthesia/analgesia
Experimental therapy
Antibiotics (poly-therapy)
Fluids
Blood products
Vasopressors/Inotropes
Sedation/analgesia
Baseline medication regimen
Adjunct therapies (e.g. steroids, heparin)
 Outcomes Non-mortality surrogate
Short term
Organ failure (often single)
Molecular biomarkers (common)
Organ histology
Mortality
Short and long term
ICU/hospital length of stay
Validated multi-organ failure score
Molecular biomarkers (rare)
Organ histology (very rare)
Research methodology
 Biostatistics Lack of sample size calculation Study powered to detect difference in pre-specified outcome
 Reduce bias Randomization rare
Lack of blinding
Randomization
Double-blinded
 Standardization Single centre
Variations in practice
Multicentre
Shared protocol
 Reporting Inconsistent
Incomplete
Difficult to synthesize
Required
Comprehensive
Conducive to systematic review
  1. There are knowledge gaps in construct validity and research methodology between preclinical models and the human condition of sepsis