Model-based clinical utility of pharmacogenetic testing and its potential population impact on the use of essential medicines in Zimbabwe

Abstract

Introduction Pharmacogenomic-related adverse drug reactions and treatment failure contribute to global morbidity. Evidence for PGx-guided therapy in sub-Saharan Africa remains limited with few implementation studies. This study evaluated the potential clinical utility and projected population-level impact of pharmacogenomic testing in Zimbabwe. Methodology A cross-sectional analysis used the Zimbabwe Essential Medicines List, DPWG guidelines, Zimbabwean genotype/phenotype data, and locally approved Summary of Product Characteristics. For the actionable gene–drug pairs identified, the number needed to genotype values were calculated from DPWG-defined absolute risk reduction and local genotype-phenotype frequencies. Potential clinical utility was assessed using the Clinical Implication Score framework and compared with Dutch population data. Results Among 308 medicines screened, 30 (9.7%) contained actionable pharmacogenomic biomarkers, corresponding to 38 gene–drug pairs, all classified as vital or essential medicines. Lower NNG values were observed for UGT1A1–atazanavir (5), UGT1A1–irinotecan (9), CYP2B6–efavirenz (26), and CYP2C9–phenytoin (25), whereas 61% of gene–drug pairs had NNG values > 1,000 compared with 47% in the Dutch population. Overall, 81.6% of PGx recommendations were concordant across populations, while 21.1% were reclassified, primarily due to differences in local genetic profiles and the limited inclusion of PGx information in the Zimbabwean SmPCs, with 42% lacking PGx information compared with 24% in the Dutch dataset. Conclusion Many essential medicines in Zimbabwe have actionable pharmacogenomic biomarkers, but gaps in local genomic guidance remain. Strengthening local evidence generation and PGx implementation is essential.