Returning research results in children: Parental Preferences and Expert Oversight

描述（由申请人提供）：当被问及是否希望收到在基因组研究过程中发现的关于自己的个人研究结果时，大多数人表示他们更喜欢收到所有结果，包括那些有效性和可操作性有限的结果。这些偏好与专家的建议形成鲜明对比，专家们担心如果返回可疑的结果，可能会造成混乱和直接伤害，因此通常建议只返回高有效性和可操作性的结果。在这个项目中，我们将寻求解决这种紧张关系，通过实证探索参与者的偏好在多大程度上可以可靠地引导个人研究成果的回报，并可以纳入一个治理结构，围绕成果的回报，最大限度地减少伤害。我们有能力通过波士顿儿童医院“基因合作伙伴关系”（TGP）收集关于这个问题的数据，这是一个新颖的儿科研究登记处，结合了基因库，CHB电子病历和可扩展的计算机系统，以确定研究参与者父母返回结果的偏好，并最终返回这些结果。TGP在大规模基因组研究中也是独一无二的，因为参与者同意接受他们的个人研究结果。认识到监督是至关重要的，以便在道德上返回研究结果给参与者，我们已经建立了一个医疗和伦理专家小组（知情队列监督委员会，或ICOB），以建议TGP的结果应该和不应该返回。当我们开始返回研究结果时，我们建议建立一个证据基础，通过确定参与者偏好是否以及如何被纳入ICOB对结果返回的监督来解决参与者偏好和专家意见之间的紧张关系。我们研究的参与者将被随机分配到三种方法中的一种来设置他们的偏好（“全部”或“没有”结果，使用结果类型的检查表，或交互式教育工具，然后使用检查表）。我们将为参与者提供假设的研究结果，以确定他们是否完全理解他们所陈述的偏好对研究结果的影响，以及是否有一种新颖的互动教育工具可以帮助参与者设置更真实地反映他们实际偏好的偏好。我们还将使用假设结果和焦点小组相结合的方法来研究参与者对ICOB的个人研究成果回报标准的看法。对于从全外显子组测序返回实际个人结果的参与者，我们将确定对接受实际个人研究结果的TGP参与者的心理和行为影响，以及设置偏好的方法是否会影响效果。在本研究结束时，遗传研究知识库将更好地理解将参与者偏好纳入研究成果回报管理的重要性，以及实现这一目标的最佳方法。

DESCRIPTION (provided by applicant): When individuals are queried about whether or not they wish to receive individual research results about themselves that are discovered in the course of genomic research, the majority indicate that they prefer receiving all results, including those that are of limited validity and actionability. These preferences are in sharp contrast to the recommendations of experts who are wary of the potential for confusion and outright harm if questionable results are returned, and thus generally recommend returning only results of high validity and actionability. In this project, we will seek to resolve this tension by empirically exploring the extent to which participant preferences can reliably guide the return of individual research results, and can be incorporated into a governance structure around the return of results which minimizes harm. We are well positioned to gather data on this issue through the Children's Hospital Boston "The Gene Partnership" (TGP), a novel pediatric research registry combining genetic banking, access to CHB electronic medical records, and scalable computer-based systems to ascertain preferences for return of results from the parents of research participants and, ultimately, to return those results. TGP is also unique among large-scale genomic studies, as participants have consented to receive their individual research results. Recognizing that oversight is essential in order to ethically return research results to participants, we have established a panel of medical and ethical experts (the Informed Cohort Oversight Board, or ICOB) to advise TGP on which results should and should not be returned. As we begin to return research results, we propose to build an evidence base to resolve the tension between participant preferences and expert opinion by determining if, and how, participant preferences can be incorporated into the ICOB's oversight of return of results. Participants in our study will be randomized to one of three methods to set their preferences ("all" or "no" results, using a checklist of types of results, or an interactive educational tool and then a checklist). We will provide participants with hypothetical research results to determine whether they fully understand the implications of their stated preferences for research results to receive, and if a novel interactive educational tool helps participants set preferences that more truly reflect their actual preferences. We will also use a combination of hypothetical results and focus groups to study participants' views on the ICOB's criteria for return of individual research results. For participants in whom there are actual individual results to return from whole exome sequencing we will determine the psychological and behavioral effects on TGP participants who receive actual individual research results, and if the method of setting preferences impacts on the effects. At the end of this study, genetic research repositories will better understand the importance of incorporating participant preferences into the governance around return of research results, and the best approaches to accomplish this.