Analytics of the clinical implementation of pharmacogenomics testing in 12 758 individuals

Dear Editor, Pharmacogenomics (PGx) testing is still not widely accepted in routine medical practice, with one of the major obstacles being the lack of evidence to support its clinical benefit.1,2 In the Chinese population, large-scale comprehensive analytics of clinical PGx testing are still lacking.3,4 Thus, we analysed clinical PGx testing for personalised drug treatment in 12,758 Chinese patients at Xiangya Hospital of Central South University, which is one of the first institutions to conduct clinical PGx testing in China. SEE PDF] TABLE 1 Drug-gene pairs and level of evidence Drug* Genes* Level of evidence# N (%) Clopidogrel CYP2C19 A 3,192 (10.89) Proton pump inhibitor CYP2C19 A 113 (0.39) Warfarin CYP2C9/VKROC1 A 4,106 (14.01) Tacrolimus CYP3A5 A 167 (0.57) Fluorouracil DPYD A 1,053 (3.59) Statins SLCO1B1 A 817 (2.79) Irinotecan UGT1A1 B 113 (0.39) Angiotensin-converting enzyme inhibitor ACE B 2,316 (7.90) Methotrexate MTHFR B 1,081 (3.69) Tamoxifen CYP2D6 B 123 (0.42) Cisplatin TPMT B 5 (0.02) Fluorouracil TYMS B 124 (0.42) Cisplatin GSTP1 C 1,352 (4.61) Statins APOE C 85 (0.29) Beta-blocker ADRB1 C 2,241 (7.65) Gemcitabine CDA C 582 (1.99) Paclitaxel CYP1B1 C 974 (3.32) Sulfonylurea CYP2C9 C 953 (3.25) Angiotensin receptor blocker CYP2C9 C 2,181 (7.44) Paclitaxel MDR1 C 310 (1.06) Pemetrexed MTHFR C 113 (0.39) Calcium channel blocker NPPA C 2,241 (7.65) Diuretic NPPA C 2,241 (7.65) Metformin OCT2 C 970 (3.31) Thiazolidinedione PPAR-γ C 970 (3.31) * The drug-gene variants pairs were determined based on the following considerations: 1. established evidence from published literature, especially in the Chinese population; 2. annotations from FDA, PharmGKB, CPIC and other clinical guidelines (for example, NCCN and ACCP); 3. the existence of functional or tag SNPs for key pharmacogenes; and 4. specific genes or variants under investigating in our institute. # Level of evidence was important for giving drug dosing adjustment recommendations or risk warnings. The patients were most likely to benefit from testing. [...]analysis was conducted in detail. TABLE 2 Results of the base-case analysis Parameters Warfarin* Clopidogrel# Irinotecan$ Genotype-guided dosing Standard dosing Genotype-guided dosing Standard dosing Genotype-guided dosing Standard dosing Cost per patient per year (US$) 466.8713 385.2739 892.9846 350.9054 19 680.8570 19 567.4206 Incremental cost 81.5974 542.0792 113.4364 QALY gained per patient year 0.7133 0.6978 0.6567 0.6383 0.7837 0.7656