Quantify the current and projected mortality and economic burden of antimicrobial resistance, diagnose the market failure preventing new antibiotic development, and assess the evidence base for policy interventions that could restore the pipeline.

Systematic review of AMR mortality and morbidity studies using GRAM methodology across 204 countries. Economic burden modeled using OECD multi-sector macroeconomic model. gov, and pharmaceutical company R&D disclosures. Market failure analysis using standard public goods framework applied to antibiotic economics.

Policy intervention evidence synthesized from 22 national AMR action plans and 6 natural experiments (Sweden antibiotic stewardship, UK subscription payment model pilot, US GAIN Act).

AMR is responsible for 4.95 million deaths annually (GRAM 2024), making it the third leading cause of death globally — above HIV/AIDS and malaria combined. 70% of deaths occur in LMICs with weakest antibiotic stewardship. By 2050, AMR is projected to cause 10 million deaths/year and $100 trillion in cumulative economic damage if current trends continue.

5B average development cost. Since 2000, 12 of 18 large pharmaceutical companies have exited antibiotic R&D. The current pipeline has 43 antibiotics in clinical development — only 13 targeting WHO priority pathogens, and only 2 with novel mechanisms of action.

At the current attrition rate, we will have no effective treatment for carbapenem-resistant Enterobacterales (CRE) within 15-20 years.

Interventions with evidence: (1) UK subscription payment model pilot — NHS pays a fixed annual fee per antibiotic regardless of volume used, decoupling revenue from sales volume. Early results show 10x improvement in developer ROI projections. (2) BARDA-style push funding for clinical trials — reduces developer risk for late-stage trials.

(3) Coordinated international delinked incentive fund of $1B/antibiotic approval meeting WHO priority criteria — modeled by BCG to restore pipeline viability if adopted by G7.