Delanne J, Nambot S, Chassagne A, Putois O, Pelissier A, Peyron C, Gautier E, Thevenon J, Cretin E, Bruel A L, Goussot V, Ghiringhelli F, Boidot R, Tran Mau-Them F, Philippe C, Vitobello A, Demougeot L, Vernin C, Lapointe A S, Bardou M, Luu M, Binquet C, Lejeune C, Joly L, Juif C, Baurand A, Sawka C, Bertolone G, Duffourd Y, Sanlaville D, Pujol P, Geneviève D, Houdayer F, Thauvin-Robinet C, Faivre L
Centre de Génétique et Centre de Référence Maladies Rares Anomalies du Développement de l'Interrégion Est, Hôpital d'Enfants, CHU, Dijon, France; FHU TRANSLAD, Centre Hospitalier Universitaire et Université de Bourgogne-Franche Comté, Dijon, France; Equipe GAD « Génétique des Anomalies du Développement », UMR INSERM 1231, Université de Bourgogne, Dijon, France.
FHU TRANSLAD, Centre Hospitalier Universitaire et Université de Bourgogne-Franche Comté, Dijon, France; CIC-IT Inserm 808, CHU de Besançon et Université de Bourgogne-Franche Comté, Besançon, France.
Eur J Med Genet. 2019 Jun;62(6):103529. doi: 10.1016/j.ejmg.2018.08.010. Epub 2018 Aug 28.
With the development of next generation sequencing, beyond identifying the cause of manifestations that justified prescription of the test, other information with potential interest for patients and their families, defined as secondary findings (SF), can be provided once patients have given informed consent, in particular when therapeutic and preventive options are available. The disclosure of such findings has caused much debate. The aim of this work was to summarize all opinion-based studies focusing on SF, so as to shed light on the concerns that this question generate. A review of the literature was performed, focusing on all PubMed articles reporting qualitative, quantitative or mixed studies that interviewed healthcare providers, participants, or society regarding this subject. The methodology was carefully analysed, in particular whether or not studies made the distinction between actionable and non-actionable SF, in a clinical or research context. From 2010 to 2016, 39 articles were compiled. A total of 14,868 people were interviewed (1259 participants, 6104 healthcare providers, 7505 representatives of society). When actionable and non-actionable SF were distinguished (20 articles), 92% of respondents were keen to have results regarding actionable SF (participants: 88%, healthcare providers: 86%, society: 97%), against 70% (participants: 83%, healthcare providers: 62%, society: 73%) for non-actionable SF. These percentages were slightly lower in the specific situation of children probands. For respondents, the notion of the «patient's choice» is crucial. For healthcare providers, the importance of defining policies for SF among diagnostic lab, learning societies and/or countries is outlined, in particular regarding the content and extension of the list of actionable genes to propose, the modalities of information, and the access to information about adult-onset diseases in minors. However, the existing literature should be taken with caution, since most articles lack a clear definition of SF and actionability, and referred to hypothetical scenarios with limited information to respondents. Studies conducted by multidisciplinary teams involving patients with access to results are sadly lacking, in particular in the medium term after the results have been given. Such studies would feed the debate and make it possible to measure the impact of such findings and their benefit-risk ratio.
随着下一代测序技术的发展，除了确定证明进行该检测合理的临床表现的病因外，一旦患者给予知情同意，尤其是在有治疗和预防选择的情况下，还可以提供对患者及其家属可能有潜在兴趣的其他信息，即定义为次要发现（SF）的信息。此类发现的披露引发了诸多争论。这项工作的目的是总结所有关注次要发现的基于观点的研究，以阐明这个问题所引发的担忧。我们对文献进行了综述，重点关注所有在PubMed上发表的定性、定量或混合研究，这些研究就该主题采访了医疗保健提供者、参与者或社会各界。我们仔细分析了研究方法，特别是研究在临床或研究背景下是否区分了可采取行动的和不可采取行动的次要发现。从2010年到2016年，共收集了39篇文章。总共采访了14,868人（1259名参与者、6104名医疗保健提供者、7505名社会代表）。当区分可采取行动的和不可采取行动的次要发现时（20篇文章），92%的受访者渴望获得关于可采取行动的次要发现的结果（参与者：88%，医疗保健提供者：86%，社会：97%），而对于不可采取行动的次要发现，这一比例为70%（参与者：83%，医疗保健提供者：62%，社会：73%）。在儿童先证者的特定情况下，这些百分比略低。对受访者而言，“患者选择”的概念至关重要。对医疗保健提供者而言，概述了在诊断实验室、学术团体和/或国家中为次要发现制定政策的重要性，特别是关于可采取行动基因列表的内容和范围、信息模式以及获取关于未成年人成年后发病疾病信息的问题。然而，现有文献应谨慎对待，因为大多数文章对次要发现和可采取行动性缺乏明确的定义，并且向受访者提及的是信息有限的假设情景。令人遗憾的是，缺乏由多学科团队进行的、让患者能够获取结果的研究，特别是在给出结果后的中期。此类研究将为这场争论提供依据，并有可能衡量此类发现的影响及其效益风险比。
