Returning Individual Genetic Research Results to Parents and Children

描述（由申请人提供）：本申请涉及广泛的挑战领域（02）生物伦理学，02-HL-101：向研究参与者提供遗传研究结果的伦理和实践指南。人类基因组图谱使研究人员能够发现基因型和表型之间的新关系，并为基因组知情的医疗决策提供了基础，这将导致有针对性的诊断和治疗，减少变异性，最大限度地提高疗效，并最大限度地减少不良反应。由于基因组研究产生的信息对健康具有更大的意义，人们正在形成一种共识，即需要从伦理上恢复基因组信息。本提案的目的是了解基因组研究参与者在参与者是儿童而信息接收者是父母的情况下对返回研究结果的态度。我们将利用我们在波士顿儿童医院（CHB）的小组发起的一个大型基因型-表型项目，该项目基于我们开发的基因组研究的新范式-知情队列。知情队列是一个模型，参与者的道德招募到一个纵向的基因型-表型登记和调和的“悖论”，维护参与者的隐私，但提供的结果。我们将CHB知情队列模型的实施称为"基因合作项目"（GPP）。GPP是一项纵向基因型-表型登记研究，其通过CHB个人控制健康记录（PCHR）使用消息传递系统，以促进将研究结果披露给参与者。"知情队列监督委员会"（ICOB）将对将结果反馈给参与者进行关键监督。虽然儿童的入学似乎存在额外的伦理障碍，但我们认为儿科医院中发生的“家庭单位”的自然参与是GPP的优势。虽然我们已经实施了GPP，但我们不知道什么因素会最大限度地提高参与者和家庭的利益和吸引力。因此，我们提出了GPP和消息传递系统的多步骤评估。我们不知道父母如何看待他们收到的关于他们孩子的研究结果的研究。为了解决这个问题，我们将评估父母是否有兴趣参与针对其子女的基因型-表型研究，并确定他们是否希望从研究中获得有关其子女的遗传信息。我们也不知道参与者在消息传递发生时会如何感知。因此，我们将评估参加GPP的参与者的父母使用基于PCHR的消息传递系统的情况。最后，一个运作良好的ICOB对于成功返回研究结果的过程至关重要，但我们不知道ICOB将如何运作。由于需要进一步开展工作，以确保ICOB是一个可行的决策模式，我们将建立"知情队列监督委员会"。从拟议的项目中获得的关于将研究结果道德地返还给参与者的知识将是至关重要的，因为我们正在走向一种模式，即个人直接受益于他们参与的基因组研究，并最终受益于基因组医学。该项目解决了与将遗传信息归还给参与基因组研究的儿童的父母有关的伦理问题。至关重要的是，基因组研究的参与者从他们参与的研究中受益，特别是如果研究结果与他们目前或未来的健康有关。然而，这种研究信息的返回需要以确保结果有效性的方式进行，并且是深思熟虑和敏感的。该项目的目标是了解父母对接受遗传研究结果的态度，并确定监督委员会的有效性，该委员会将解决如何道德地将结果返还给参与者的问题。这项研究将是重要的遗传研究走向参与者真正意识到他们是研究的一部分的好处。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (02) Bioethics, 02-HL-101: Informing the ethical and practical guidelines for providing genetic research results to study participants. The mapping of the human genome has allowed researchers to discover new relationships between genotype and phenotype, and has provided the basis for genome-informed medical decision-making that will lead to diagnoses and therapies that are targeted, have reduced variability, maximize efficacy, and minimize adverse effects. As information of greater health significance is generated by genomic research, there is an emerging consensus that the ethical return of genomic information will be needed. The goal of this proposal is to understand the attitudes of participants in genomic research towards the return of research results in the setting where the participant is a child and the receiver of the information is the parent. We will take advantage of a large genotype-phenotype project initiated by our group at Children's Hospital Boston (CHB) based on the Informed Cohort, a new paradigm for genomic research that we developed. The Informed Cohort is a model for the ethical recruitment of participants into a longitudinal genotype-phenotype registry and reconciles the "paradox" of maintaining participant privacy, yet providing results. We call the implementation of the Informed Cohort model at CHB the "Gene Partnership Project" (GPP). GPP is a longitudinal genotype-phenotype registry that uses a messaging system through the CHB personally- controlled health record (PCHR) to facilitate the disclosure of research results back to the participants. The "Informed Cohort Oversight Board" (ICOB) will provide the crucial oversight of the communication of results back to participants. While the enrollment of children might seem to present additional ethical obstacles, we see the natural participation of the "family unit" that occurs in pediatric hospital as an advantage for GPP. While we have implemented GPP, we do not know what factors will maximize its benefit and appeal for participants and families. We therefore propose a multi-step evaluation of the GPP and the messaging system. We do not know how parents view studies where they receive research results back on their children. To address this issue we will assess the interest of parents to participate in a genotype-phenotype study focused on their children, and determine if they would want to receive genetic information back from the study about their child. We also do not know how participants will perceive the messaging when it occurs. Thus, we will assess the use of the PCHR-based messaging system by parents of participants enrolled in GPP. Finally, a functioning ICOB will be paramount for the process of returning research results to be successful, yet we do not know how the ICOB will function. Since further work is required to ensure that the ICOB is a workable model for decision-making, we will develop the "Informed Cohort Oversight Board". The knowledge gained from the proposed project on the ethical return of research results to participants will be critical as we move towards a paradigm where individuals directly benefit from the genomic research they participate in, and eventually from genomic medicine. This project addresses the ethical issues associated with the return of genetic information to the parents of children participating in genomic research. It is critical that participants in genomic research benefit from the studies that they are participating in, especially if there are research results that pertain to their current or future health. Yet the return of such research information needs to be done in a manner that assures validity of the results, and is thoughtful and sensitive. The goals of this project are to understand parental attitudes toward receiving genetic research results back on their children, and to determine the effectiveness of an oversight board that will address the questions of how to ethical return results to participants. This study will be important as genetic research moves towards participants truely realizing the benefits of the research they are a part of.