Bonini Katherine E, Smith Hadley Stevens, Bonkowski Emily S, Berkman Benjamin E, Jamal Leila
Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.
Public Health Genomics. 2025;28(1):19-33. doi: 10.1159/000541301. Epub 2024 Nov 9.
Though genomic science has rapidly advanced, efforts to demonstrate the population-level utility of genomics have been slow to follow. It has long been argued that the family is an important unit of significance in genomics, yet it has been challenging to address this in clinical care. This is apparent in how hospital administrators and clinicians in the United States typically approach cascade screening, the process of notifying and offering genetic testing to at-risk relatives of a patient with a hereditary condition. The most common notification approach is proband-led contact, in which the index patient is responsible for communicating a health risk to their relatives. This model has been associated with suboptimal outcomes. In contrast, recent research has shown that system-led contact, in which healthcare or public health institutions initiate communication to relatives with the proband's consent, has been associated with increased clinical utility and acceptability.
With the needs of hospital administrators and clinicians in mind, we revisit normative questions about the appropriate way to notify relatives about their potentially elevated risk of developing an actionable disease. We review evidence demonstrating that system-led direct contact of relatives is feasible and acceptable. We further argue that system-led contact of relatives eligible for cascade screening is ethically justified if these programs are designed with public input, have an opt-out provision, and are implemented for conditions that meet specific criteria which we propose in this article.
In this article, we emphasize the usefulness of public health ethics frameworks to inform the design of system-led contact programs. Beyond this, we make the case that such programs are necessary to realize the population utility of genomic medicine equitably.
尽管基因组科学迅速发展，但证明基因组学在人群层面的实用性的努力却进展缓慢。长期以来，人们一直认为家庭是基因组学中一个重要的有意义的单位，但在临床护理中解决这一问题一直具有挑战性。这在美国医院管理人员和临床医生通常进行级联筛查的方式中很明显，级联筛查是指通知患有遗传病的患者的高危亲属并为其提供基因检测的过程。最常见的通知方式是先证者主导的联系，即索引患者负责将健康风险告知其亲属。这种模式与不理想的结果相关。相比之下，最近的研究表明，系统主导的联系，即医疗保健或公共卫生机构在征得先证者同意后主动与亲属沟通，与更高的临床实用性和可接受性相关。
考虑到医院管理人员和临床医生的需求，我们重新审视关于以适当方式通知亲属其患可采取行动的疾病的潜在风险增加的规范性问题。我们回顾了证据，证明系统主导的亲属直接联系是可行且可接受的。我们进一步认为，如果这些项目在公众参与下设计、有退出条款，并针对本文中我们提出的符合特定标准的疾病实施，那么对符合级联筛查条件的亲属进行系统主导的联系在伦理上是合理的。
在本文中，我们强调公共卫生伦理框架对指导系统主导的联系项目设计的有用性。除此之外，我们认为此类项目对于公平实现基因组医学的人群效用是必要的。
