The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Department of Medical Ethics and Health Policy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
JAMA Netw Open. 2022 Aug 1;5(8):e2225980. doi: 10.1001/jamanetworkopen.2022.25980.
Genomic medicine holds promise to revolutionize care for critically ill infants by tailoring treatments for patients and providing additional prognostic information to families. However, measuring the utility of genomic medicine is not straightforward and has important clinical and ethical implications.
To review the ways that researchers measure or neglect to measure the utility of genomic medicine for critically ill infants.
This systematic review included prospective full-text studies of genomic medicine of both whole exome and genome sequencing in critically ill infants younger than 1 year. PubMed, Embase, Scopus, and Cochrane Library databases, the Cochrane Database of Systematic Reviews, and the ClinicalTrials.gov register were searched with an English language restriction for articles published from the inception of each database through May 2022. Search terms included variations of the following: gene, sequencing, intensive care, critical care, and infant. From the included articles, information on how utility was defined and measured was extracted and synthesized. Information was also extracted from patient cases that authors highlighted by providing additional information. Spearman rank-order correlation was used to evaluate the association between study size and utility.
Synthesized data from the 21 included studies reflected results from 1654 patients. A mean of 46% (range, 15%-72%) of patients had a positive genetic test result, and a mean of 37% (range, 13%-61%) met the criteria for experiencing utility. Despite heterogeneity in how studies measured and reported utility, a standardized framework was created with 5 categories of utility: treatment change, redirection of care, prognostic information, reproductive information, and screening or subspecialty referral. Most studies omitted important categories of utility, notably personal utility (patient-reported benefits) (20 studies [95%]), utility of negative or uncertain results (15 [71%]), and disutility (harms) (20 [95%]). Studies disproportionally highlighted patient cases that resulted in treatment change. Larger studies reported substantially lower utility (r = -0.65; P = .002).
This systematic review found that genomic medicine offered various categories of utility for a substantial proportion of critically ill infants. Studies measured utility in heterogeneous ways and focused more on documenting change than assessing meaningful benefit. Authors' decisions about which cases to highlight suggest that some categories of utility may be more important than others. A more complete definition of utility that is used consistently may improve understanding of potential benefits and harms of genetic medicine.
基因组医学有望通过为患者量身定制治疗方案并为家属提供额外的预后信息，从而彻底改变对危重症婴儿的护理方式。然而，衡量基因组医学的效用并不简单，这具有重要的临床和伦理意义。
综述研究人员衡量或忽略衡量基因组医学对危重症婴儿效用的方法。
本系统评价纳入了对年龄小于 1 岁的危重症婴儿进行全外显子组或基因组测序的基因组医学的前瞻性全文研究。对从每个数据库建立开始到 2022 年 5 月发表的文章，在 PubMed、Embase、Scopus 和 Cochrane Library 数据库、Cochrane 系统评价数据库和 ClinicalTrials.gov 注册处进行了英语语言限制的搜索。检索词包括以下内容的变体：基因、测序、重症监护、危重病和婴儿。从纳入的文章中提取并综合了关于效用如何定义和衡量的信息。还从作者通过提供额外信息突出显示的患者病例中提取了信息。使用 Spearman 秩相关评估研究规模与效用之间的关联。
综合来自 21 项纳入研究的数据反映了 1654 名患者的结果。平均有 46%（范围，15%-72%）的患者有阳性基因检测结果，平均有 37%（范围，13%-61%）符合获得效用的标准。尽管研究在衡量和报告效用方面存在异质性，但创建了一个标准化框架，其中包括 5 类效用：治疗改变、护理方向改变、预后信息、生殖信息和筛查或专科转诊。大多数研究遗漏了重要的效用类别，特别是患者报告的益处（个人效用）（20 项研究[95%]）、阴性或不确定结果的效用（15 项[71%]）和不良效应（损害）（20 项[95%]）。研究不成比例地强调了导致治疗改变的患者病例。较大的研究报告的效用明显较低（r=-0.65；P=0.002）。
本系统评价发现，基因组医学为大量危重症婴儿提供了各种类别的效用。研究以不同的方式衡量效用，并且更侧重于记录改变，而不是评估有意义的益处。作者关于突出哪些病例的决定表明，某些类别的效用可能比其他效用更重要。更全面、一致使用的效用定义可能会提高对遗传医学潜在益处和危害的理解。
