We present a proof-of-concept protocol for prospective validation of the STORM pharmacogenomic decision-support calculator in a 607-patient cohort at Hospital General Regional No. 1, IMSS, Mérida, Yucatán, Mexico. The protocol defines a 30-gene panel (expanding from STORM v3.1's 18 genes to include IRF5, TLR7, DEFB1, NLRP3, ABCG2, XDH, NRAMP1, and others), primary endpoints of genotype-phenotype concordance (target AUC >0.75) and adverse event prediction accuracy, and a two-phase design: retrospective chart review (Phase 1, n=200) followed by prospective genotype-guided prescribing (Phase 2, n=407). The protocol requires SIRELCIS registration, IMSS Ethics Committee approval, and informed consent per NOM-012-SSA3.
STORM (Stochastic Therapy Optimization for Rheumatology in Mexico) v3.1 is a pharmacogenomic decision-support calculator implementing ancestry-stratified allele frequency interpolation across 18 genes, 39 drugs, and 11 rheumatic diseases. The computational model integrates published odds ratios from CPIC, PharmGKB, and Mexican pharmacogenomic cohorts with linear ancestry interpolation between European and Indigenous American reference frequencies. Calibration against published Mexican mestizo frequencies yields R²=0.986. Deployed on RheumaScore.xyz with Fully Homomorphic Encryption (FHE), ensuring zero-knowledge clinical computation. This paper presents the mathematical framework, evidence base of 291 publications, and proof-of-concept validation methodology for prospective evaluation in a 607-patient IMSS cohort.
