The Global Compatibility Index (GCI): A Variance-Weighted Pharmacogenomic Scoring System Demonstrates Near-Perfect Cross-Mode Consistency (ICC = 0.994) and Improves Warfarin Dose Prediction Over the CPIC Algorithm in 5,475 Patients Across Four Continents, with Multi-Drug Validation Across 10 Independent Datasets
Abstract
Abstract Background. Adverse drug reactions (ADRs) account for 10–15% of all hospital admissions globally, with the majority attributable to variants in pharmacogenomically actionable genes. Current decision tools require genomic sequencing infrastructure unavailable in over 80% of the world's healthcare settings, creating a profound global equity gap in personalised prescribing. I developed the Global Compatibility Index (GCI), a variance-weighted adaptive scoring formula that integrates genomic, biomarker, epidemiologic, interaction, and family history factors across four data-richness operating modes, from full genomic sequencing to demographics only. Methods. GCI is defined as GCI(d,p) = [Σ i (V i × W i )] × Πⱼ(Cⱼ) × Conf(σ), where five adaptive factors (V_G: genomic activity score; V_P: organ function; V_E: population epidemiologic prior; V_I: drug interaction burden; V_F: family history) are weighted by data availability with weights constrained to sum to 1.0, and Bayesian confidence bands widen proportionally with missing data. Primary validation used the International Warfarin Pharmacogenetics Consortium dataset (IWPC; n = 5,475; CYP2C9 and VKORC1 genotyped). Secondary validations included: FDA FAERS 2019–2025 (n = 589,461 patient-drug episodes; 12 drug classes; Mode 4); ITPC tamoxifen cohort (n = 4,973; CYP2D6); ISPC antidepressant cohort (n = 865); Lancet African warfarin genotype study (n = 658); Translational Pharmacogenetics Project (TPP) clinical decision…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 589,461 participants or records.
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