临床外显子测序中偶然发现报告标准 - 比利时遗传中心专业实践和观点的焦点小组研究。
Criteria for reporting incidental findings in clinical exome sequencing - a focus group study on professional practices and perspectives in Belgian genetic centres.
机构信息
Department of Public Health and Primary Care, Philosophy of Medicine and Ethics Research Group, Ghent University, Campus Heymans (UZ Gent), Corneel Heymanslaan 10 - Building 6K3, 9000, Ghent, Belgium.
Department of Philosophy and Moral Sciences, Bioethics Institute Ghent, Ghent University, Ghent, Belgium.
出版信息
BMC Med Genomics. 2019 Aug 20;12(1):123. doi: 10.1186/s12920-019-0561-0.
BACKGROUND
Incidental and secondary findings (IFs and SFs) are subject to ongoing discussion as potential consequences of clinical exome sequencing (ES). International policy documents vary on the reporting of these findings. Discussion points include the practice of unintentionally identified IFs versus deliberately pursued SFs, patient opt-out possibilities and the spectrum of reportable findings. The heterogeneity of advice permits a non-standardised disclosure but research is lacking on actual reporting practices. Therefore, this study assessed national reporting practices for IFs and SFs in clinical ES and the underlying professional perspectives.
METHODS
A qualitative focus group study has been undertaken, including professionals from Belgian centres for medical genetics (CMGs). Data were analysed thematically.
RESULTS
All Belgian CMGs participated in this study. Data analysis resulted in six main themes, including one regarding the reporting criteria used for IFs. All CMGs currently use ES-based panel testing. They have limited experience with IFs in clinical ES and are cautious about the pursuit of SFs. Two main reporting criteria for IFs were referred to by all CMGs: the clinical significance of the IF (including pathogenicity and medical actionability) and patient-related factors (including the patient's preference to know and patient characteristics). The consensus over the importance of these criteria contrasted with their challenging interpretation and application. Points of concern included IFs' pathogenicity in non-symptomatic persons, IFs concerning variants of uncertain significance, the requirement and definition of medical actionability and patient opt-out possibilities. Finally, reporting decisions were guided by the interaction between the clinical significance of the IF and patient characteristics. This interaction questions the possible disclosure of findings with context-dependent and personal utility, such as IFs concerning a carrier status. To evaluate the IF's final relevance, a professional and case-by-case deliberation was considered essential.
CONCLUSIONS
The challenging application of reporting criteria for IFs results in diversified practices and policy perspectives within Belgian CMGs. This echoes international concerns and may have consequences for effective policy recommendations.
背景
偶然发现和次要发现（IF 和 SF）是临床外显子组测序（ES）潜在后果的持续讨论主题。国际政策文件对这些发现的报告存在差异。讨论要点包括无意识别的 IF 与有意追求的 SF 之间的区别、患者选择退出的可能性以及可报告发现的范围。建议的多样性允许非标准化的披露，但缺乏关于实际报告实践的研究。因此，本研究评估了临床 ES 中 IF 和 SF 的国家报告实践以及潜在的专业观点。
方法
进行了一项定性焦点小组研究，包括来自比利时医学遗传学中心（CMG）的专业人员。数据进行了主题分析。
结果
所有比利时 CMG 都参与了这项研究。数据分析产生了六个主要主题，包括一个关于 IF 报告标准的主题。所有 CMG 目前都使用基于 ES 的面板测试。他们在临床 ES 中对 IF 经验有限，对 SF 的追求持谨慎态度。所有 CMG 都提到了 IF 的两个主要报告标准：IF 的临床意义（包括致病性和医学可操作性）和患者相关因素（包括患者了解的意愿和患者特征）。所有 CMG 都对这些标准的重要性达成共识，尽管这些标准的解释和应用具有挑战性。关注的问题包括非症状患者 IF 的致病性、涉及意义不明的变异的 IF、医疗可操作性的要求和定义以及患者选择退出的可能性。最后，报告决策受到 IF 的临床意义与患者特征之间相互作用的指导。这种相互作用质疑了可能带有上下文相关和个人效用的发现的披露，例如涉及携带者状态的 IF。为了评估 IF 的最终相关性，被认为需要进行专业的、逐案的审议。
结论
IF 报告标准的挑战性应用导致比利时 CMG 内部存在多样化的实践和政策观点。这反映了国际关注的问题，可能对有效的政策建议产生影响。
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