From Access to Appropriate Use: Reimbursement Design for Pathogen Nucleic Acid Diagnostics across Six Health Systems, 2014–2026

Background Pathogen nucleic acid diagnostics answer questions that culture, antigen detection and serology cannot answer within the treatment-decision window — slow-growing and fastidious organisms, paucibacillary disease, and genotypic resistance — yet are persistently reimbursed below that value; we ask whether that mismatch is transitional or structural. Methods We compare six health systems (China, the United States, Germany, France, England, Japan) under a most-different-systems design, tracing three index technology classes defined by target scope — single-pathogen detection with or without a resistance-conferring variant; multi-pathogen targeted detection by multiplex or isothermal amplification or panel enrichment with sequencing; and untargeted metagenomic sequencing of the primary specimen — through a three-gates framework (approval, price assignment, coverage) using primary policy documents, 2014–2026, under confidence-tiered verification. Results All six systems impose the same three gates, but the binding gate differs: China's price-item gate is being removed by the 2026 national price-item guideline (trial), which standardises item definitions but not price levels, so the binding constraint migrates to insurance listing rather than disappearing; the United States binds at clinical-utility evidence; Germany at coverage. A "double squeeze" of inpatient diagnosis-related-group bundling and outpatient price compression (Medicare's ratcheted PAMA repricing, repeatedly deferred; China's volume-based procurement cuts of 47–77%; Japan's FY2014 256-item fee cut) suppresses adoption of cost-effective tests. Five innovation carve-outs echoing the coverage-with-evidence-development concept underperform for diagnostics: Germany's inpatient innovation channel (NUB) integrated 105 of more than 3,400 methods into regular payment in 2005–2020 (single peer-reviewed source); Medicare's molecular-panel coverage policy excludes metagenomic sequencing from its scope, with no affirmative coverage elsewhere. Regulatory review itself ranges from months (Japan's targets; US 510(k) goals) to multiple years (China's Class III elapsed times; EU notified-body backlogs). For metagenomic sequencing, Gate 1 is a laboratory-accreditation regime rather than product review, and the longest lags sit at the approval–payment interface (median 5.7 years from FDA authorisation to nominal Medicare coverage in a 2016–2019 cohort; diagnostics' lags were shorter). Conclusion The reimbursement gap is structural and is best explained by the externalisation of diagnostic value across budget silos; closing it requires diagnostic-specific payment design coupled to prescriber competency in test selection.