Ackerman Sara L, Koenig Barbara A
a Department of Social and Behavioral Sciences , University of California , San Francisco.
b Institute for Health and Aging, University of California , San Francisco.
AJOB Empir Bioeth. 2018 Jan-Mar;9(1):48-57. doi: 10.1080/23294515.2017.1405095. Epub 2017 Dec 21.
Increasingly used for clinical purposes, genome and exome sequencing can generate clinically relevant information that is not directly related to the reason for testing (incidental or secondary findings). Debates about the ethical implications of secondary findings were sparked by the American College of Medical Genetics (ACMG) 2013 policy statement, which recommended that laboratories report pathogenic alterations in 56 genes. Although wide variation in laboratories' secondary findings policies has been reported, little is known about its causes.
We interviewed 18 laboratory directors and genetic counselors at 10 U.S. laboratories to investigate the motivations and interests shaping secondary findings reporting policies for clinical exome sequencing. Analysis of interview transcripts and laboratory documents was informed by sociological theories of standardization.
Laboratories varied widely in terms of the types of secondary findings reported, consent-form language, and choices offered to patients. In explaining their adaptation of the ACMG report, our participants weighed genetic information's clinical, moral, professional, and commercial value in an attempt to maximize benefits for patients and families, minimize the costs of sequencing and analysis, adhere to professional norms, attract customers, and contend with the uncertain clinical implications of much of the genetic information generated.
Nearly all laboratories in our study voluntarily adopted ACMG's recommendations, but their actual practices varied considerably and were informed by laboratory-specific judgments about clinical utility and patient benefit. Our findings offer a compelling example of standardization as a complex process that rarely leads simply to uniformity of practice. As laboratories take on a more prominent role in decisions about the return of genetic information, strategies are needed to inform patients, families, and clinicians about the differences between laboratories' practices and ensure that the consent process prompts a discussion of the value of additional genetic information for patients and their families.
基因组和外显子组测序越来越多地用于临床目的，它能够产生与检测原因无直接关联的临床相关信息（偶然或次要发现）。美国医学遗传学学会（ACMG）2013年的政策声明引发了关于次要发现伦理影响的讨论，该声明建议实验室报告56个基因中的致病性改变。尽管已报道实验室的次要发现政策存在很大差异，但其原因却鲜为人知。
我们采访了美国10家实验室的18位实验室主任和遗传咨询师，以调查影响临床外显子组测序次要发现报告政策的动机和利益因素。访谈记录和实验室文件的分析以标准化的社会学理论为依据。
各实验室在报告的次要发现类型、同意书措辞以及为患者提供的选择方面差异很大。在解释他们对ACMG报告的调整时，我们的受访者权衡了遗传信息的临床、道德、专业和商业价值，试图为患者和家庭最大化利益，最小化测序和分析成本，遵守专业规范，吸引客户，并应对所产生的许多遗传信息不确定的临床意义。
我们研究中的几乎所有实验室都自愿采纳了ACMG的建议，但其实际做法差异很大，并受到实验室对临床效用和患者利益的特定判断的影响。我们的研究结果提供了一个令人信服的例子，说明标准化是一个复杂的过程，很少简单地导致实践的统一。随着实验室在遗传信息反馈决策中发挥更突出的作用，需要采取策略让患者、家庭和临床医生了解各实验室做法的差异，并确保同意过程促使人们讨论额外遗传信息对患者及其家庭的价值。
