Gammon B L, Kraft S A, Michie M, Allyse M
Biomedical Ethics Program, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Stanford University Center for Biomedical Ethics, 1215 Welch Road, Modular A, Stanford, CA 94305, USA.
Ethics Med Public Health. 2016 Jul-Sep;2(3):334-342. doi: 10.1016/j.jemep.2016.07.006.
The recent introduction of cell-free DNA-based non-invasive prenatal screening (cfDNA screening) into clinical practice was expected to revolutionize prenatal testing. cfDNA screening for fetal aneuploidy has demonstrated higher test sensitivity and specificity for some conditions than conventional serum screening and can be conducted early in the pregnancy. However, it is not clear whether and how clinical practices are assimilating this new type of testing into their informed consent and counselling processes. Since the introduction of cfDNA screening into practice in 2011, the uptake and scope have increased dramatically. Prenatal care providers are under pressure to stay up to date with rapidly changing cfDNA screening panels, manage increasing patient demands, and keep up with changing test costs, all while attempting to use the technology responsibly and ethically. While clinical literature on cfDNA screening has shown benefits for specific patient populations, it has also identified significant misunderstandings among providers and patients alike about the power of the technology. The unique features of cfDNA screening, in comparison to established prenatal testing technologies, have implications for informed decision-making and genetic counselling that must be addressed to ensure ethical practice.
This study explored the experiences of prenatal care providers at the forefront of non-invasive genetic screening in the United States to understand how this testing changes the practice of prenatal medicine. We aimed to learn how the experience of providing and offering this testing differs from established prenatal testing methodologies. These differences may necessitate changes to patient education and consent procedures to maintain ethical practice.
We used the online American Congress of Obstetricians and Gynecologists Physician Directory to identify a systematic sample of five prenatal care providers in each U.S. state and the District of Columbia. Beginning with the lowest zip code in each state, we took every fifth name from the directory, excluding providers who were retired, did not currently practice in the state in which they were listed, or were not involved in a prenatal specialty. After repeating this step twice and sending a total of 461 invitations, 37 providers expressed interest in participating, and we completed telephone interviews with 21 providers (4.6%). We developed a semi-structured interview guide including questions about providers' use of and attitudes toward cfDNA screening. A single interviewer conducted and audio-recorded all interviews by telephone, and the interviews lasted approximately 30 minutes each. We collaboratively developed a codebook through an iterative process of transcript review and code application, and a primary coder coded all transcripts.
Prenatal care providers have varying perspectives on the advantages of cfDNA screening and express a range of concerns regarding the implementation of cfDNA screening in practice. While providers agreed on several advantages of cfDNA, including increased accuracy, earlier return of results, and decreased risk of complications, many expressed concern that there is not enough time to adequately counsel and educate patients on their prenatal screening and testing options. Providers also agreed that demand for cfDNA screening has increased and expressed a desire for more information from professional societies, labs, and publications. Providers disagreed about the healthcare implications and future of cfDNA screening. Some providers anticipated that cfDNA screening would decrease healthcare costs when implemented widely and expressed optimism for expanded cfDNA screening panels. Others were concerned that cfDNA screening would increase costs over time and questioned whether the expansion to include microdeletions could be done ethically.
The perspectives and experiences of the providers in this study allow insight into the clinical benefit, burden on prenatal practice, and potential future of cfDNA screening in clinical practice. Given the likelihood that the scope and uptake of cfDNA screening will continue to increase, it is essential to consider how these changes will affect frontline prenatal care providers and, in turn, patients. Providers' requests for additional guidance and data as well as their concerns with the lack of time available to explain screening and testing options indicate significant potential issues with patient care. It is important to ensure that the clinical integration of cfDNA screening is managed responsibly and ethically before it expands further, exacerbating pre-existing issues. As prenatal screening evolves, so should informed consent and the resources available to women making decisions. The field must take steps to maximize the advantages of cfDNA screening and responsibly manage its ethical issues.
最近基于游离DNA的无创产前筛查（cfDNA筛查）引入临床实践，有望给产前检测带来变革。胎儿非整倍体的cfDNA筛查在某些情况下已显示出比传统血清筛查更高的检测灵敏度和特异性，且可在妊娠早期进行。然而，尚不清楚临床实践是否以及如何将这种新型检测纳入其知情同意和咨询流程。自2011年cfDNA筛查引入实践以来，其应用范围和规模急剧增加。产前护理提供者面临压力，要跟上快速变化的cfDNA筛查项目，满足患者不断增加的需求，并跟上检测成本的变化，同时还要负责任且合乎道德地使用该技术。虽然关于cfDNA筛查的临床文献已表明其对特定患者群体有益，但也指出了提供者和患者对该技术效能存在重大误解。与既定的产前检测技术相比，cfDNA筛查的独特特征对知情决策和遗传咨询有影响，必须加以解决以确保合乎道德的实践。
本研究探讨了美国无创基因筛查前沿的产前护理提供者的经验，以了解这种检测如何改变产前医学实践。我们旨在了解提供和开展这种检测的经验与既定的产前检测方法有何不同。这些差异可能需要改变患者教育和同意程序，以维持合乎道德的实践。
我们使用美国妇产科医师协会在线医师名录，在美国每个州和哥伦比亚特区系统抽取五名产前护理提供者。从每个州邮编最低的开始，我们从名录中每隔五个名字选取一个，排除已退休、不在其列出所在州执业或未从事产前专科的提供者。重复此步骤两次后，共发出461份邀请，37名提供者表示有兴趣参与，我们对21名提供者（4.6%）进行了电话访谈。我们制定了一份半结构化访谈指南，包括关于提供者对cfDNA筛查的使用和态度的问题。由一名访谈者通过电话进行并录音所有访谈，每次访谈持续约30分钟。我们通过对转录本进行反复审查和应用编码的迭代过程共同制定了一个编码手册，由一名主要编码员对所有转录本进行编码。
产前护理提供者对cfDNA筛查的优势有不同看法，并对cfDNA筛查在实践中的实施表达了一系列担忧。虽然提供者认同cfDNA的几个优势，包括准确性提高、结果回报更早以及并发症风险降低，但许多人担心没有足够时间就产前筛查和检测选项对患者进行充分咨询和教育。提供者还一致认为对cfDNA筛查的需求增加，并表示希望从专业协会、实验室和出版物获得更多信息。提供者对cfDNA筛查的医疗影响和未来存在分歧。一些提供者预计广泛实施cfDNA筛查将降低医疗成本，并对扩大cfDNA筛查项目表示乐观。另一些人则担心随着时间推移cfDNA筛查会增加成本，并质疑纳入微缺失检测在伦理上是否可行。
本研究中提供者的观点和经验有助于深入了解cfDNA筛查在临床实践中的临床益处、对产前实践的负担以及潜在的未来。鉴于cfDNA筛查的范围和应用可能会继续增加，必须考虑这些变化将如何影响一线产前护理提供者，进而影响患者。提供者对额外指导和数据的请求以及他们对缺乏时间解释筛查和检测选项的担忧表明在患者护理方面存在重大潜在问题。在cfDNA筛查进一步扩大并加剧现有问题之前，确保其在临床中的整合得到负责任且合乎道德的管理非常重要。随着产前筛查的发展，知情同意以及为做出决策的女性提供的资源也应随之发展。该领域必须采取措施最大限度地发挥cfDNA筛查的优势，并负责任地管理其伦理问题。
