BioFRAM PGx, an Implementation Proposal for Pharmacogenetics in the Spanish National Health System
Francisco Arias-Aragón, Carmen Mata-Martín, Alba Sánchez-Redondo, Jesús Novalbos, Miguel Ángel Seguido, Francisco Abad-Santos, Mar Hernaez, Mercè Brunet, David Hansoe Heredero-Jung, Alejandro de la Sota-Pérez, María Isidoro-García, Almudena Gil-Rodriguez, Alba Barral-Raña, Olalla Maroñas, Gladys Guadalupe Olivera Pasquini, Enrique G. Zucchet, María José Herrero, José Manuel Dodero-Anillo, Alicia Alba Máñez, María José Pedrosa-Martínez, Adrián Llerena,Background/Objectives: Pharmacogenetics (PGx) may improve drug safety and effectiveness, but its integration into routine care remains heterogeneous across the Spanish National Health System (NHS). This article presents BioFRAM PGx, a multicentre implementation framework that defines the methodological and operational basis for subsequent observational validation in cardiovascular and mental-health care settings. Methods: The framework was developed by healthcare centres from eight Spanish Autonomous Communities through a structured review of PharmGKB/ClinPGx clinical annotations, CPIC and DPWG guidelines, and national regulatory resources. Gene–drug pairs were prioritized according to clinical actionability, therapeutic relevance, applicability to the Spanish population, and analytical feasibility. BioFRAM PGx defines a panel of seven pharmacogenes and 35 drugs, standardized genotyping and phenotype-assignment procedures, pharmacovigilance and clinical variables, healthcare-resource measures, and centralized data management. The proposed non-interventional validation phase includes adults receiving at least one selected drug in hospital or primary-care settings, with a minimum six-month follow-up. PGx results are not returned to clinicians and do not modify treatment. Its primary objective is to assess the predictive value of PGx genotyping for adverse drug reactions (ADRs); secondary objectives include ADR incidence and implementation feasibility. Results: The main outputs are the proposed multicentre observational design, the prioritized gene–drug panel, harmonized analytical and pharmacovigilance workflows, standardized data domains, and a centralized data-management strategy. No patient-level clinical, implementation, or economic outcomes are presented. Conclusions: BioFRAM PGx provides a structured multicentre framework for harmonizing pharmacogenetic procedures across the Spanish NHS. Its clinical effectiveness, influence on prescribing, scalability, and economic outcomes remain to be assessed in subsequent studies.