Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
Julius Center, Department of Medical Humanities, University Medical Center Utrecht, Utrecht, the Netherlands.
BMC Med Ethics. 2023 Nov 11;24(1):98. doi: 10.1186/s12910-023-00977-y.
Massively parallel sequencing techniques, such as whole exome sequencing (WES) and whole genome sequencing (WGS), may reveal unsolicited findings (UFs) unrelated to the diagnostic aim. Such techniques are frequently used for diagnostic purposes in pediatric cases of developmental delay (DD). Yet policy guidelines for informed consent and return of UFs are not well equipped to address specific moral challenges that may arise in these children's situations.
In previous empirical studies conducted by our research group, we found that it is sometimes uncertain how children with a DD will develop and whether they could come to possess capacities for autonomous decision-making in the future. Parents sometimes felt this brought them into a Catch-22 like situation when confronted with choices about UFs before undergoing WES in trio-analysis (both the parents' and child's DNA are sequenced). An important reason for choosing to consent to WES was to gain more insight into how their child might develop. However, to make responsible choices about receiving or declining knowledge of UFs, some idea of their child's future development of autonomous capacities is needed. This undesirable Catch-22 situation was created by the specific policy configuration in which parents were required to make choices about UFs before being sequencing (trio-analysis). We argue that this finding is relevant for reconfiguring current policies for return of UFs for WES/WGS and propose guidelines that encompass two features. First, the informed consent process ought to be staged. Second, differing guidelines are required for withholding/disclosing a UF in cases of DD appropriate to the level of confidence there is about the child's future developmental of autonomous capacities.
When combined with a dynamic consent procedure, these two features of our guidelines could help overcome significant moral challenges that present themselves in the situations of children undergoing genomic sequencing for clarifying a DD.
大规模平行测序技术，如外显子组测序（WES）和全基因组测序（WGS），可能会揭示与诊断目的无关的意外发现（UFs）。这些技术经常被用于儿科发育迟缓（DD）病例的诊断目的。然而，关于知情同意和意外发现回报的政策指南还没有很好地解决可能在这些儿童情况下出现的具体道德挑战。
在我们研究小组进行的先前实证研究中，我们发现，有时不确定患有 DD 的儿童将如何发展，以及他们将来是否有可能拥有自主决策的能力。当父母在进行三联分析（同时对父母和孩子的 DNA 进行测序）之前面临 UF 选择时，他们有时会感到自己陷入了一个类似“两难”的境地。选择同意 WES 的一个重要原因是为了更深入地了解孩子的发展情况。然而，要对接受或拒绝 UF 知识做出负责任的选择，就需要对孩子未来自主能力的发展有一定的了解。这种不理想的“两难”局面是由父母在进行测序（三联分析）之前就必须对 UF 做出选择的特定政策配置所造成的。我们认为，这一发现与重新配置当前 WES/WGS 意外发现回报政策有关，并提出了包含两个特征的指南。首先，知情同意过程应该分阶段进行。其次，对于 DD 病例中 UF 的隐瞒/披露，需要根据对孩子未来自主能力发展的信心程度，制定不同的准则。
当与动态同意程序相结合时，我们指南的这两个特征可以帮助克服在为澄清 DD 对儿童进行基因组测序的情况下出现的重大道德挑战。
