Project Summary/Abstract Options to reduce bleeding risk in persons living with hemophilia A are expanding. The issue is important because the expense of factor concentrates, the most expensive drugs per beneficiary under Medicare Part B, account for >80-90% of discounted lifetime hemophilia treatment costs (-$12-18 million per person). Options currently include i) standard half-life factor products, ii) extended half-life factor products, iii) non-factor substitutes, and iv) gene therapy. Analyses of optimal prophylactic strategies for persons living with hemophilia A are complicated by study heterogeneity, a result of different inclusion criteria and disease severity categories. To date, most health economic analyses have been funded by industry. A public-facing, easilyupdatable, transparent, and independent health economic model does not exist for treatment decisions faced by persons living with hemophilia A. Accordingly, the overarching goal of this research is to quantify value- and equity-informed resource allocation thresholds for subpopulations living with hemophilia A. The applicant will achieve the proposed aims of this K01 award under the guidance of established researchers who span health decision science, health policy, hematology, and pharmacoepidemiology. The applicant will create a publicfacing, transparent, and independent microsimulation model to evaluate all existing prophylactic treatment strategies for persons living with hemophilia A. He will use a combination of intermediate and advanced health decision science and pharmacoepidemiologic methodological techniques to derive equity weight thresholds, assess the value of collecting information with future studies, and quantify annualized bleed rates from realworld data. The research will make available needed information on the risks, benefits, and costs of bleed prevention strategies in persons living with hemophilia A. The proposed career development and training goals will provide the applicant with training in microsimulation, budget, and equity impact analyses, value of information research, and pharmacoepidemiology - and lay the groundwork for future research. The proposed training, infrastructure, and Yale institutional support will ensure the applicant's transition to independence.