Siena Leonardo Maria, Baccolini Valentina, Riccio Marianna, Rosso Annalisa, Migliara Giuseppe, Sciurti Antonio, Isonne Claudia, Iera Jessica, Pierri Francesco, Marzuillo Carolina, De Vito Corrado, La Torre Giuseppe, Villari Paolo
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy; Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Am J Hum Genet. 2025 Aug 7;112(8):1735-1753. doi: 10.1016/j.ajhg.2025.05.012. Epub 2025 Jun 12.
Polygenic risk scores (PRSs) represent a promising innovation in the context of precision health, but their benefits for patients and healthcare systems remain unclear. This systematic review examined the methods used to quantify the costs and benefits of PRS-based approaches across different healthcare contexts, summarizing current evidence and identifying challenges. A systematic search of three databases was conducted, and full economic evaluations related to any intervention based on polygenic risk stratification strategies were included (PROSPERO CRD42023442780). Quality was assessed using the Quality of Health Economic Studies instrument. Studies were grouped into three categories (cancer, cardiovascular disease, and other diseases), and key methodological features and characteristics were extracted. A total of 24 cost-utility analyses of generally high quality were included: 16 studies focused on cancer, five on cardiovascular disease, and three on other diseases. Studies on cancer mainly aimed to optimize screening programs, while in the other fields, PRSs were mostly used to refine eligibility for preventive therapies. Analyses were robust, but they mostly relied on hypothetical cohorts, had limited generalizability, paid insufficient attention to implementation aspects-including the delivery model-and considered only clinical benefits. Despite a positive trend toward cost effectiveness following PRS implementation, several challenges remain. These include the limited use of real-world data, issues of representativeness, and gaps in accounting for implementation costs, as well as long-term health and non-health benefits. Further research and pilot studies are needed to evaluate both the costs and benefits of PRS applications across diverse populations for multiple health outcomes simultaneously.
多基因风险评分（PRSs）在精准健康领域代表着一项颇具前景的创新，但它们对患者和医疗保健系统的益处仍不明确。本系统评价考察了在不同医疗保健背景下用于量化基于PRS方法的成本和效益的方法，总结了当前证据并识别了挑战。对三个数据库进行了系统检索，并纳入了与基于多基因风险分层策略的任何干预措施相关的全面经济评估（PROSPERO CRD42023442780）。使用卫生经济研究质量工具评估质量。研究被分为三类（癌症、心血管疾病和其他疾病），并提取了关键的方法学特征和特点。总共纳入了24项质量普遍较高的成本效用分析：16项研究聚焦于癌症，5项聚焦于心血管疾病，3项聚焦于其他疾病。关于癌症的研究主要旨在优化筛查项目，而在其他领域，PRSs大多用于完善预防性治疗的资格标准。分析较为稳健，但大多依赖于假设队列，普遍性有限，对实施方面（包括交付模式）关注不足，且仅考虑了临床效益。尽管实施PRS后呈现出成本效益的积极趋势，但仍存在一些挑战。这些挑战包括真实世界数据的使用有限、代表性问题、实施成本核算方面的差距，以及长期健康和非健康效益。需要进一步的研究和试点研究来同时评估PRS在不同人群中针对多种健康结局应用的成本和效益。
