Growing efforts have focused on uncovering pharmacogenetic contributors that heighten the likelihood of clozapine-associated agranulocytosis or granulocytopenia (CIAG). Three markers—the SLCO1B3-SCLO1B7 polymorphism (rs149104283) and specific single–residue substitutions in the human leukocyte antigen (HLA) region, HLA-DQB1 (126Q) and HLA-B (158T)—have been linked to elevated CIAG risk. In this analysis, we examined both the clinical impact and economic implications of supplementing existing HLA-based screening with the SLCO1B3-SCLO1B7 variant as an expanded pharmacogenomic (PGx) approach, and assessed outcomes in a population of individuals with schizophrenia using clozapine as a third-line therapy. The decision framework incorporated deterministic and probabilistic sensitivity assessments to estimate total costs and quality-adjusted life-years (QALYs). Over a 10-year period, the current monitoring program was evaluated against a PGx-based pathway in which all patients receive genetic testing before beginning clozapine. Incorporating the SLCO1B3-SCLO1B7 variant increased CIAG detection sensitivity from 36.0% to 43.0%, reduced specificity from 89.0% to 86.9%, and raised the probability of being cost-effective from 74.1% to 87.8%. The incremental cost-effectiveness ratio was £16,215 per QALY, staying underneath the conventional threshold (£30,000 or US$50,000 per QALY). These findings indicate that adding the SLCO1B3-SCLO1B7 marker to HLA alleles improves pre-emptive test performance and enhances both the clinical and economic utility of PGx-guided clozapine treatment.
