Ethical Legal and Social Implications of Translational Psychiatric Genomics Research

 描述（由申请人提供）：该项目采用了多方法，跨学科的方法，结合民族志参与观察，访谈研究方法，伦理，法律的，和公共政策分析。本项目的两个目标是：1）确定 精神病基因组学领域在试图将大规模GWAS的发现转化为临床有用信息时将面临的伦理、法律的和政策挑战，以及2）就如何应对这些挑战提出基于证据的建议。为了实现这些目标，我将使用，作为一个案例研究，第一次尝试翻译大规模的精神病基因组学GWAS的发现，耐药性精神病（GTRP）研究的基因组学。GTRP将对1,000名患有难治性精神病（TRP）的住院患者进行全外显子组测序（WES）。GTRP的目标是识别与TRP相关的基因组变异，并确定这些基因组测试是否会产生任何临床可操作的信息，这些信息可能有助于改善特定患者参与者的心理健康护理。 我建议研究GTRP的经验，以解决三个研究目标的理解翻译精神病基因组学研究所面临的挑战，严重的精神疾病患者至关重要。目标1将是项目的指导研究阶段，目标2和3将是独立研究阶段。 目的1a采用民族志参与观察和访谈的方法来研究的因素，影响GTRP研究人员的决策过程中，设计和进行WES同意过程和返回的结果（RoR）的组成部分，他们的研究。目标1b采用伦理分析来评价GTRP研究的设计，包括WES同意过程和RoR组件。目标1c采用法律的和政策分析，以审查监管框架，目前到位，以保护制度化的严重精神病患者参加翻译精神病WES研究。 目标2a是根据目标1进行的一项经验性检查，采用访谈方法研究GTRP患者参与者、患者参与者的法律的监护人或授权代表（LG/AR）、患者参与者的心理健康临床医生以及GTRP将在其中进行的心理健康机构的官员的观点和偏好。访谈将评估他们对如何处理WES同意过程、选择返回的结果、RoR同意过程、实际RoR程序以及WES结果的RoR后管理的看法。目标2b采用法律的分析来检查LG/AR、临床医生和精神卫生机构在研究人员返回WES结果后（RoR后管理）承担何种法律的责任（如果有的话）。 目的3采用伦理和法律的分析，探讨应用法律的信托关系模型（FRM）的含义，以确定不同各方对翻译精神病基因组学研究中患者参与者的伦理责任。这项工作将参考在目标1和2中收集的数据。

 DESCRIPTION (provided by applicant): This project employs a multi-method, transdisciplinary approach that combines ethnographic participant- observation, interview research methods, ethical, legal, and public policy analyses. The two goals of the present project are 1) to identify the ethical, legal, and policy challenges that the field of psychiatric genomics will face when trying to translate the findings of large-scale GWAS into clinically useful information, and 2) to make evidence-based recommendations about how to address these challenges. To achieve these goals, I will use, as a case study, one of the first attempts to translate large-scale psychiatric genomics GWAS findings, the Genomics of Treatment-Resistant Psychosis (GTRP) study. GTRP will perform whole exome sequencing (WES) in a sample of 1,000 institutionalized patients who suffer from treatment-resistant psychosis (TRP). GTRP's goals are to identify genomic variants associated with TRP, and ascertain whether any clinically actionable information emerges from these genomic tests that could help improve mental health care for particular patient-participants. I propose to study GTRP's experience to address three research aims critical to understanding the challenges faced in translational psychiatric genomics research with severely mentally ill patients. Aim 1 will be the mentored research phase of the project, and Aims 2 and 3 will be the independent research phases. Aim 1a employs ethnographic participant-observation and interview methods to study the factors that influence GTRP researchers' decision-making process while designing and conducting the WES consent process and the return of results (RoR) components of their study. Aim 1b employs ethical analysis to evaluate the design of the GTRP study, including the WES consent process and RoR components. Aim 1c employs legal and policy analyses to examine the regulatory framework currently in place to protect institutionalized severely mentally ill patients who participate in translational psychiatric WES research. Aim 2a is an empirical examination informed by Aim 1 that employs interview methods to study the views and preferences of GTRP patient-participants, patient-participants' legal guardians or authorized representatives (LG/AR), patient-participants' mental health clinicians, and officials of the mental health institutions in which GTRP will take place. The interviews will assess their perspectives regarding how to handle the WES consent process, selection of results to return, RoR consent process, actual RoR procedure, and the Post-RoR management of WES findings. Aim 2b employs legal analysis to examine what kind of legal responsibility, if any, LG/ARs, clinicians, and mental health institutions, assume regarding the management of WES findings once these are returned by researchers (Post-RoR management). Aim 3 employs ethical and legal analyses to explore the implications of applying a legal Fiduciary Relationship Model (FRM) for defining the ethical responsibilities that different parties hold towards patient- participants in translational psychiaric genomics research. This work will be informed by the data collected in Aims 1 and 2.