Returning research results in children: Parental Preferences and Expert Oversight

描述（由申请人提供）：当个人被问及他们是否希望收到在基因组研究过程中发现的关于他们自己的个人研究结果时，大多数人表示他们希望收到所有结果，包括那些有限有效性和可操作性的结果。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造成混淆和直接伤害，因此通常建议只返回高有效性和可操作性的结果。在本项目中，我们将通过实证探索参与者偏好在多大程度上能够可靠地指导个人研究结果的回报，并将其纳入围绕结果回报的治理结构中，从而最大限度地减少伤害，从而寻求解决这种紧张关系。通过波士顿儿童医院的“基因伙伴关系”（TGP），我们可以很好地收集有关这一问题的数据。TGP是一种新型儿科研究登记，结合了基因库、CHB电子医疗记录和可扩展的基于计算机的系统，以确定研究参与者的父母对返回结果的偏好，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个人的研究结果。认识到监督对于将研究成果伦理地返还给参与者至关重要，我们成立了一个医学和伦理专家小组（知情队列监督委员会，ICOB），就哪些结果应该返还、哪些不应该返还向TGP提出建议。当我们开始返回研究结果时，我们建议建立一个证据基础，通过确定是否以及如何将参与者偏好纳入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。在我们的研究中，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，使用结果类型清单，或使用交互式教育工具，然后使用清单）。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，以及是否有一种新的互动教育工具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的组合来研究参与者对ICOB返回个人研究结果的标准的看法。对于从全外显子组测序中获得实际个体结果的参与者，我们将确定对获得实际个体研究结果的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，基因研究库将更好地理解将参与者偏好纳入研究成果回报治理的重要性，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. PUBLIC HEALTH RELEVANCE: It is important that participants in genomic research benefit from the studies that they are participating in, especially if research results pertain to their current or future health, by choosing what types of individual research results they want to receive (setting preferences). On the other hand, experts fear that participants do not truly understand the implications of their choice of individual research results to receive, suggesting that it is unrealistic to incorporate participant preferences in the return of individual research results. In this project, we will explore the extent to which participant preferences can truly be used to guide governance around return of individual research results.