Korngiebel Diane M, McMullen Carmit K, Amendola Laura M, Berg Jonathan S, Davis James V, Gilmore Marian J, Harding Cary O, Himes Patricia, Jarvik Gail P, Kauffman Tia L, Kennedy Kathleen A, Simpson Dana Kostiner, Leo Michael C, Lynch Frances L, Quigley Denise I, Reiss Jacob A, Richards C Sue, Rope Alan F, Schneider Jennifer L, Goddard Katrina A B, Wilfond Benjamin S
Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, Washington.
Kaiser Permanente Northwest Center for Health Research, Portland, Oregon.
Am J Med Genet A. 2016 Mar;170(3):565-73. doi: 10.1002/ajmg.a.37513.
As genome or exome sequencing (hereafter genome-scale sequencing) becomes more integrated into standard care, carrier testing is an important possible application. Carrier testing using genome-scale sequencing can identify a large number of conditions, but choosing which conditions/genes to evaluate as well as which results to disclose can be complicated. Carrier testing generally occurs in the context of reproductive decision-making and involves patient values in a way that other types of genetic testing may not. The Kaiser Permanente Clinical Sequencing Exploratory Research program is conducting a randomized clinical trial of preconception carrier testing that allows participants to select their preferences for results from among broad descriptive categories rather than selecting individual conditions. This paper describes (1) the criteria developed by the research team, the return of results committee (RORC), and stakeholders for defining the categories; (2) the process of refining the categories based on input from patient focus groups and validation through a patient survey; and (3) how the RORC then assigned specific gene-condition pairs to taxonomy categories being piloted in the trial. The development of four categories (serious, moderate/mild, unpredictable, late onset) for sharing results allows patients to select results based on their values without separately deciding their interest in knowing their carrier status for hundreds of conditions. A fifth category, lifespan limiting, was always shared. The lessons learned may be applicable in other results disclosure situations, such as incidental findings.
随着基因组或外显子组测序（以下简称基因组规模测序）越来越多地融入标准医疗中，携带者检测成为一项重要的潜在应用。使用基因组规模测序进行携带者检测可以识别大量病症，但选择评估哪些病症/基因以及披露哪些结果可能会很复杂。携带者检测通常发生在生殖决策的背景下，并且以其他类型的基因检测可能不会涉及的方式涉及患者价值观。凯撒医疗集团临床测序探索性研究项目正在进行一项孕前携带者检测的随机临床试验，该试验允许参与者从广泛的描述性类别中选择他们对结果的偏好，而不是选择个别病症。本文描述了：（1）研究团队、结果反馈委员会（RORC）和利益相关者为定义类别所制定的标准；（2）根据患者焦点小组的意见完善类别以及通过患者调查进行验证的过程；（3）RORC随后如何将特定的基因-病症对分配到试验中正在试点的分类类别。用于结果共享的四个类别（严重、中度/轻度、不可预测、迟发性）的制定使患者能够根据自己的价值观选择结果，而无需分别决定他们对了解自己针对数百种病症的携带者状态的兴趣。第五个类别，寿命受限，总是会被共享。所吸取的经验教训可能适用于其他结果披露情况，例如偶然发现。
