Closing the Missing Middle between Pharmacogenomic Association, Functional Evidence, Prescribing Recommendations, and Patient-Level Therapeutic Decisions in Routine Care

Pharmacogenomics has generated clinically relevant gene–drug associations, increasingly standardized variant interpretations, prescribing recommendations, and implementation infrastructures. Nevertheless, a persistent translational discontinuity remains between identifying an association and making a defensible therapeutic decision for an individual patient. This discontinuity arises because association credibility, variant and haplotype resolution, functional interpretation, genotype-to-phenotype translation, recommendation formation, patient-context assessment, and decision delivery answer different scientific and clinical questions. Treating any one of these components as sufficient can obscure uncertainty and overstate decision readiness. This Original Evidence-Translation Framework Article proposes the Pharmacogenomic Evidence Bridge as a conceptual architecture for closing this missing middle. The framework represents translation as a sequence of non-substitutable evidence states connected by explicit transition gates. It distinguishes established pharmacogenomic concepts from proposed relationships governing functional resolvability, recommendation translatability, patient-context compatibility, and decision-use readiness. Cross-cutting mechanisms address evidence provenance, version control, uncertainty documentation, ancestry and sex transferability, evidence updating, and conflict resolution. Clinical decision support is positioned as an evidence-delivery and contextualization layer rather than an autonomous therapeutic authority. The framework generates testable propositions concerning evidentiary concordance, phenoconversion, transferability, workflow conditionality, and the validation requirements of patient-specific computational representations. Its evaluation would require analytical, functional, clinical, informatics, implementation, and equity-focused studies conducted in intended populations and therapeutic settings. The proposed architecture does not establish clinical utility, regulatory acceptance, universal applicability, or deployment readiness. Its original contribution is to make the intermediate evidentiary transitions between pharmacogenomic discovery and patient-level therapeutic use explicit, examinable, and governable.