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：向研究参与者提供基因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，这些决策将导致有针对性的诊断和治疗，降低变异性，最大限度地提高疗效，并将不良反应降至最低。由于基因组研究产生了对健康具有更大意义的信息，因此出现了一种新的共识，即基因组信息的伦理回归将是必要的。这项建议的目的是了解基因组研究参与者对返回研究结果的态度，在参与者是儿童，信息的接受者是父母的情况下。我们将利用我们在波士顿儿童医院(CHB)发起的一个大型基因-表型项目，该项目基于我们开发的一种新的基因组研究范式--知情队列。知情队列是道德招募参与者进入纵向基因-表型注册的模型，并调和了维护参与者隐私但提供结果的“悖论”。我们将在CHB实施知情队列模式称为“基因伙伴计划”(GPP)。GPP是一个纵向的基因-表型登记系统，它通过CHB个人控制的健康记录(PCHR)使用消息传递系统，以促进向参与者披露研究结果。“知情群体监督委员会”(ICOB)将对将结果反馈给参与者进行至关重要的监督。虽然儿童的入学似乎带来了额外的伦理障碍，但我们认为儿科医院发生的“家庭单位”的自然参与对GPP来说是一个优势。虽然我们已经实施了GPP，但我们不知道哪些因素将使其对参与者和家庭的好处和吸引力最大化。因此，我们建议对GPP和报文传送系统进行多步骤评估。我们不知道父母如何看待他们收到关于孩子的研究结果的研究。为了解决这个问题，我们将评估父母参与以他们的孩子为重点的基因-表型研究的兴趣，并确定他们是否希望从研究中获得关于他们孩子的遗传信息。我们也不知道当消息发生时，参与者将如何看待它。因此，我们将评估参加GPP的参与者的家长使用基于PCHR的消息传递系统的情况。最后，一个正常运作的ICOB对于成功地返回研究结果将是至关重要的，但我们不知道ICOB将如何运作。由于需要进一步的工作来确保ICOB成为一个可行的决策模式，我们将建立“知情群体监督委员会”。从拟议的项目中获得的关于研究结果对参与者的伦理回报的知识将是至关重要的，因为我们正在走向一种范式，在这种范式中，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返回给参与基因组研究的儿童的父母有关的伦理问题。基因组研究的参与者从他们所参与的研究中受益是至关重要的，特别是如果有与他们目前或未来健康相关的研究结果。然而，这种研究信息的返还需要以一种确保结果有效性的方式进行，并且是经过深思熟虑和敏感的。这个项目的目标是了解父母对收到关于他们孩子的基因研究结果的态度，并确定一个监督委员会的有效性，该委员会将解决如何将结果返回给参与者的问题。随着基因研究朝着参与者真正认识到他们所参与的研究的好处的方向发展，这项研究将是重要的。

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.