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

Abstract 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.