BackgroundWe describe and validate a new simulation framework addressing important limitations of the Simulated Allocation Models (SAMs) long used to project population effects of transplant policy changes. MethodsWe developed the Computational Open-source Model for Evaluating Transplantation (COMET), an agent-based model simulating interactions of individual donors and candidates over time to project population outcomes. COMET functionality is organized into interacting modules. Donors and candidates are synthetically generated using data-driven probability models which are adaptable to account for ongoing or hypothetical donor/candidate population trends and evolving disease management. To validate the first implementation of COMET, COMET-Lung, we attempted to reproduce lung transplant outcomes for U.S. adults from 2018-2019 and in the six months following adoption of the Composite Allocation Score (CAS) for lung transplant. ResultsSimulated (median [Interquartile Range, IQR]) versus observed outcomes for 2018-2019 were: 0.162 [0.157, 0.167] versus 0.170 waitlist deaths per waitlist year; 1.25 [1.23, 1.28] versus 1.26 transplants per waitlist year; 0.115 [0.112, 0.118] versus 0.113 post-transplant deaths per patient year; 202 [102, 377] versus 165 nautical miles travel distance. The model accurately predicted the observed precipitous decrease in transplants received by type O lung candidates in the six months following CAS implementation. ConclusionsCOMET-Lung closely reproduced most observed outcomes. The use of synthetic populations in the COMET framework paves the way for examining possible transplant policy and clinical practice changes in populations reflecting realistic future states. Its flexible, modular nature can accelerate development of features to address specific research or policy questions across multiple organs.