Introducing Polygenic Risk Scores In Clinical Practice: A Systematic Review of Economic Evaluations

Abstract Background Polygenic Risk Scores (PRS) represent a promising innovation in the context of precision health and have been studied across various settings, but their clinical utility and benefits for healthcare systems remain under debate. This systematic review examines the cost-effectiveness of PRS-based approaches across different healthcare contexts, summarizing current evidence, evaluating methodologies for costs and benefit estimation, identifying challenges in assessment models, and suggesting directions for future research. Methods A systematic search of PubMed, Scopus, and Web of Science identified all economic evaluations related to interventions based on polygenic risk stratification strategies. The quality of included studies was assessed using the Quality of Health Economic Studies (QHES) instrument. This study was supported by the EC and MUR- PNRR-M4C2-I1.3 Project PE_00000019 ‘HEAL ITALIA’. Results A total of 2,183 records were identified, of which 24 were included in the review. Among these, 16 studies focused on cancer (prostate, colorectal, breast, lung, nasopharyngeal carcinoma, and multiple tumors), five on cardiovascular diseases, two on type 2 diabetes, and one on primary open-angle glaucoma. The economic evaluations, primarily cost-utility analyses, assessed the use of PRS in screening and treatment, with variable findings on their cost-effectiveness. PRS-based strategies demonstrated higher cost-effectiveness in certain oncological, cardiovascular, and diabetes-related applications, but results were mixed for specific cancer types. Study quality ranged from 62/100 to 100/100. Conclusions Despite a positive trend in cost-effectiveness of PRS implementation, several challenges remain. These include limited real-world data, issues of representativeness, and gaps in accounting for implementation costs. Further research and pilot studies are needed to evaluate PRS applications across diverse populations and multiple health outcomes. Key messages • PRS show cost-effectiveness potential, but limited real-world validation hinders adoption. • Cost-effectiveness of PRS varies; further context- and population- specific studies are needed.