PHARMACOGENOMICS AND PERSONALIZED DRUG THERAPY: IMPLEMENTATION IN DIVERSE POPULATIONS AND REAL-WORLD EVIDENCE

Pharmacogenomics aims to tailor drug therapy based on an individual’s genetic profile, improving efficacy and reducing adverse drug reactions. While major pharmacogenomic associations have been identified for drug-metabolizing enzymes, transporters, and human leukocyte antigens, clinical implementation has been uneven across healthcare systems and populations. This review critically examines the current state of pharmacogenomic implementation, focusing on diverse ancestral populations and the role of real-world evidence in validating clinical utility. Key implementation examples include HLA-B*57:01 screening for abacavir hypersensitivity, TPMT/NUDT15 testing before thiopurine therapy, and CYP2C19-guided antiplatelet therapy. However, the majority of discovery cohorts remain of European ancestry, leading to reduced predictive accuracy and missed variants in African, Asian, Hispanic, and Indigenous populations. Star allele systems and rare variants vary significantly across populations, and polygenic scores may not transfer across ancestries. Real-world data from electronic health records, biobanks, and pragmatic trials are increasingly used to assess clinical outcomes, cost-effectiveness, and implementation barriers. Challenges include lack of standardized reporting, limited diversity in biobanks, healthcare provider education, and payer reimbursement policies. Future directions include diverse biobank initiatives, population-specific allele definition, pharmacogenomic-guided randomized trials, and integration of genomic data into clinical decision support. Achieving equitable pharmacogenomic implementation requires deliberate inclusion of underrepresented populations and robust real-world evidence generation.