EHR-driven therapeutic interchange in value-based oncology.

558 Background: Therapeutic interchange is a core component of value-based care delivery, leveraging biosimilars, 505b(2) products, and new delivery routes to improve outcomes (e.g., biosimilars: 53% market share, 53% cost reduction after 5 years), but operationalization requires technical solutions. In April 2024, the START Center for Cancer Care launched a new Electronic Health Record (EHR) with two features: (1) Substitution Groups: automatically replace biosimilar and 505(b)2 drugs based on practice-defined rules, including default preferences with insurer level overrides; and (2) Flatiron Assist (FA): a clinical decision support (CDS) tool for selecting and documenting National Comprehensive Cancer Network (NCCN)-concordant regimens, customizable with site-level preferences. This retrospective study evaluates how EHR-automated therapeutic interchange reduces manual interventions as part of a comprehensive medication management strategy. Methods: Substitution groups are based on a crosswalk of biosimilars/505(b)2 drugs with Medicare and commercial payer preferences, created by the Director of Pharmacy and revenue cycle management. When a reference product is ordered, it is replaced by payer or practice preference. START has 7 biosimilar and eleven 505(b)2 groups, each with a mix of practice and payer preferences. Preferred regimens are defined by the pharmacy and therapeutics committee based on efficacy, tolerability, availability and reimbursement, then authored into the CDS tool. As providers enter patient characteristics, treatment recommendations filter accordingly, highlighting practice preferences among NCCN-concordant options. START authored 163 preferred regimens across 17 diseases; providers ordered a preferred regimen 92% of the time when available. Orders from April 2024 - May 2025 were compared. Biosimilar substitution was available throughout; 505(b)2 substitution began in September 2024. In the prior EHR, all substitutions were manual. Results: We found automatic substitution replaced manual intervention in 2505 orders. After custom preferences, 83% (95% CI: 79-88%) of orders were for Drug A across 4 disease settings with clinical equipoise. In renal cell carcinoma (RCC), after adding a preference on 1/1/2025, ordering shifted approximately threefold to 71% (95% CI: 57–86%) for Drug A. Conclusions: EHR-automated therapeutic interchange drives measurable quality, efficiency, and financial outcomes. As oncology pharmacy operations grow more complex, automation reduces reliance on manual interventions amid workforce shortages and clinician burnout. Results. Category Time Period Biosimilars 505(b)(2) Total Substitution Groups 4/2/24 - 5/22/25 1965 549 2,505 Preferred Regimens Drug A Drug B Ratio A:B Melanoma, esophageal, gastric, and non-small cell lung cancer 4/2/24 - 5/22/25 213 43 5:1 RCC Pre-Preference 4/2 - 12/31/24 39 36 1:1 RCC Post-Preference 1/1 - 5/22/25 27 11 3:1