Evaluating the Cost-Effectiveness of Polygenic Risk Score-Guided Breast Cancer Screening Using a Discrete Event Simulation Model
Author(s)
Greg Guzauskas, MSPH, PhD1, John Graves, PhD2, Jing Hao, MPH, MS, PhD, MD3, Shawn Garbett, MS2, Josh Peterson, MD, MPH2, David L. Veenstra, PharmD, PhD4;
1The CHOICE Institute, Senior Research Scientist, Orcas, WA, USA, 2Vanderbilt University, Nashville, TN, USA, 3Geisinger Health, Danville, PA, USA, 4University of Washington, The CHOICE Institute, Seattle, WA, USA
1The CHOICE Institute, Senior Research Scientist, Orcas, WA, USA, 2Vanderbilt University, Nashville, TN, USA, 3Geisinger Health, Danville, PA, USA, 4University of Washington, The CHOICE Institute, Seattle, WA, USA
Presentation Documents
OBJECTIVES: Breast cancer (BrCA) screening is a cornerstone of early detection and prevention, yet current guidelines rely primarily on age-based criteria. Incorporating monogenic risks and polygenic risk scores (PRS) provides an opportunity to personalize screening based on genetic risk, improving efficiency and outcomes. However, the cost-effectiveness of PRS-guided strategies remains unclear. A discrete event simulation (DES) model offers a robust framework to evaluate these strategies by capturing individual variability and probabilistic uncertainty.
METHODS: The DES, developed in Microsoft Excel, simulated time-to-event processes, including time to BrCA, ovarian cancer, risk-reducing mastectomy or salpingo-oophorectomy, cancer-specific mortality, and secular mortality. Cancer incidence was predicted by PRS scores in the screening comparator, with 0.5% of women modeled as hereditary breast and ovarian cancer (HBOC) carriers. Each model run simulated 1,000 women, incorporating health state-specific costs and utilities from published literature. A preliminary probabilistic sensitivity analysis (PSA) of 500 simulations was conducted to validate incremental QALYs and life years by comparing results with the six CISNET models under analogous screening strategies.
RESULTS: Preliminary results showed that the 95% credible intervals for incremental QALYs and life years in our PSA closely overlapped with the CISNET deterministic ranges. For biennial screening (ages 40-74), the RIPS PSA model estimated 135 incremental life years (range: 130-140; CISNET: 120-160) and 115 incremental QALYs (range: 110-120; CISNET: 100-140) per 1,000 women. For biennial screening (ages 50-74), RIPS PSA estimates were 95 incremental life years (range: 90-100; CISNET: 80-120) and 82 incremental QALYs (range: 80-85; CISNET: 70-100).
CONCLUSIONS: These preliminary findings validate the utility of a DES framework for PRS-guided BrCA screening strategies. Future work involves refining outcomes and combining this model with colorectal cancer and cardiovascular disease models to assess the cost-effectiveness of PRS testing across multiple conditions.
METHODS: The DES, developed in Microsoft Excel, simulated time-to-event processes, including time to BrCA, ovarian cancer, risk-reducing mastectomy or salpingo-oophorectomy, cancer-specific mortality, and secular mortality. Cancer incidence was predicted by PRS scores in the screening comparator, with 0.5% of women modeled as hereditary breast and ovarian cancer (HBOC) carriers. Each model run simulated 1,000 women, incorporating health state-specific costs and utilities from published literature. A preliminary probabilistic sensitivity analysis (PSA) of 500 simulations was conducted to validate incremental QALYs and life years by comparing results with the six CISNET models under analogous screening strategies.
RESULTS: Preliminary results showed that the 95% credible intervals for incremental QALYs and life years in our PSA closely overlapped with the CISNET deterministic ranges. For biennial screening (ages 40-74), the RIPS PSA model estimated 135 incremental life years (range: 130-140; CISNET: 120-160) and 115 incremental QALYs (range: 110-120; CISNET: 100-140) per 1,000 women. For biennial screening (ages 50-74), RIPS PSA estimates were 95 incremental life years (range: 90-100; CISNET: 80-120) and 82 incremental QALYs (range: 80-85; CISNET: 70-100).
CONCLUSIONS: These preliminary findings validate the utility of a DES framework for PRS-guided BrCA screening strategies. Future work involves refining outcomes and combining this model with colorectal cancer and cardiovascular disease models to assess the cost-effectiveness of PRS testing across multiple conditions.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
EE142
Topic
Economic Evaluation
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology, STA: Personalized & Precision Medicine