PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：大规模平行测序技术，如全外显子组测序（WES）和全基因组测序（WGS），可能会发现与诊断目的无关的未经请求的发现（UF）。这种技术经常用于小儿发育迟缓（DD）病例的诊断目的。然而，知情同意和归还UF的政策指南并没有很好地解决这些儿童处境中可能出现的具体道德挑战。
结论：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，以及他们将来是否可以拥有自主决策的能力。在进行三重奏分析（父母和孩子的DNA都被测序）之前，父母有时会觉得在面对UF的选择时，这让他们陷入了Catch-22的境地。选择同意WES的一个重要原因是为了更深入地了解他们的孩子可能会如何发展。然而,对接收或拒绝UF知识做出负责任的选择，需要一些关于他们孩子未来自主能力发展的想法。这种不希望的Catch-22情况是由特定的策略配置造成的，在该策略配置中，要求父母在进行测序（三重分析）之前对UF进行选择。我们认为，这一发现与重新配置当前WES/WGS的UF返回政策有关，并提出包含两个功能的指南。首先,知情同意过程应该分阶段进行。第二,在DD适合儿童未来自主能力发展的信心水平的情况下，扣留/披露UF需要不同的指导方针。
结论：当与动态同意程序结合使用时，我们指南的这两个特点可以帮助克服在接受基因组测序以澄清DD的儿童中出现的重大道德挑战.
结论：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，以及他们将来是否可以拥有自主决策的能力。在进行三重奏分析（父母和孩子的DNA都被测序）之前，父母有时会觉得在面对UF的选择时，这让他们陷入了Catch-22的境地。选择同意WES的一个重要原因是为了更深入地了解他们的孩子可能会如何发展。然而,对接收或拒绝UF知识做出负责任的选择，需要一些关于他们孩子未来自主能力发展的想法。这种不希望的Catch-22情况是由特定的策略配置造成的，在该策略配置中，要求父母在进行测序（三重分析）之前对UF进行选择。我们认为，这一发现与重新配置当前WES/WGS的UF返回政策有关，并提出包含两个功能的指南。首先,知情同意过程应该分阶段进行。第二,在DD适合儿童未来自主能力发展的信心水平的情况下，扣留/披露UF需要不同的指导方针。
结论：当与动态同意程序结合使用时，我们指南的这两个特点可以帮助克服在接受基因组测序以澄清DD的儿童中出现的重大道德挑战.
