Clinical Scorecard: Biomarker-Based Predictive Enrichment in Research Involving Critically Ill Sepsis Patients: A Systematic Review

At a Glance

Key Highlights

• Sepsis mortality remains high (30–50%) despite advances in supportive care and numerous RCTs.
• Heterogeneity of treatment effect (HTE) in sepsis populations dilutes therapeutic efficacy signals in trials.
• Predictive enrichment using biomarkers (genomic, transcriptomic, proteomic, metabolomic) can identify subgroups more likely to benefit from targeted interventions.

Guideline-Based Recommendations

Diagnosis

• Use blood-based biomarkers measured at enrollment to identify biologically distinct sepsis subphenotypes.
• Apply Sepsis II or III criteria to define eligible critically ill adult patients.

Management

• Incorporate predictive enrichment strategies in clinical trials to selectively randomize patients likely to respond to specific therapies.
• Leverage biomarker profiles aligned with sepsis pathobiology to guide intervention selection.

Monitoring & Follow-up

• Monitor biomarker levels at trial enrollment to confirm eligibility and stratify patients.
• Assess primary outcomes within enriched subgroups to evaluate treatment efficacy.

Risks

• Failure to account for heterogeneity of treatment effect may lead to negative trial results and missed therapeutic benefits.
• Limited adoption of predictive enrichment may perpetuate ineffective broad-spectrum sepsis therapies.

Patient & Prescribing Data

Critically ill adult patients with sepsis or septic shock enrolled in RCTs using biomarker-based predictive enrichment

Targeted therapies may demonstrate improved efficacy when administered to biomarker-enriched subgroups, as evidenced by analogous successes in oncology and other fields.

Clinical Best Practices

• Design RCTs incorporating biomarker-based predictive enrichment to address heterogeneity in sepsis treatment response.
• Select biomarkers that reflect underlying sepsis pathobiology and have validated measurement methods.
• Use standardized sepsis definitions and rigorous trial methodologies including randomization and blinding.
• Engage multidisciplinary teams including health information specialists for comprehensive literature searches and data extraction.
• Report biomarker thresholds and rationale transparently to facilitate reproducibility and clinical translation.

References

• Surviving Sepsis Campaign
• PRISMA Statement
• PROSPERO Registration CRD420250653215
• Cochrane Risk of Bias Tool Version 2.0