Ethical Legal and Social Implications of Translational Psychiatric Genomics Research

转化精神病学基因组学研究的伦理法律和社会影响

• 批准号: 8957341
• 负责人: Gabriel Lazaro-Munoz
• 金额: $ 8.51万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8957341
• 关键词: Address; Bipolar Disorder; Caring; Case Study; Communities; Conditioned Reflex; Consensus; Consent; Data; Decision Making; Ethical Analysis; Ethics; Ethnography; Face; Genes; Genomics; Goals; Healthcare; Individual; Information Technology; Institution; Interview; Laws; Legal; Legal Guardians; Medical; Medicine; Mental Health; Mental disorders; Mentally Ill Persons; Mentors; Methods; Modeling; Participant; Patient Care; Patient Representative; Patients; Phase; Play; Policies; Policy Analysis; Population; Prevention; Procedures; Process; Protocols documentation; Psychiatric therapeutic procedure; Psychotic Disorders; Public Policy; Research; Research Methodology; Research Personnel; Resistance; Role; Sampling; Schizophrenia; Scientist; Severities; Techniques; Testing; Translating; Trust; Vulnerable Populations; Work; authority; clinical care; clinically actionable; clinically relevant; decision-making capacity; design; evidence based guidelines; exome sequencing; experience; genetic variant; genome wide association study; improved; informant; interest; legal implication; preference; public health relevance; social implication; volunteer

 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.

 描述(由申请者提供)：该项目采用多方法、跨学科的方法，结合了人种学参与者观察、访谈研究方法、伦理、法律和公共政策分析。本项目的两个目标是：1)确定 精神病学基因组学领域将面临的伦理、法律和政策挑战，当试图将大规模GWAS的发现转化为临床有用的信息时，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精神病学基因组学GWAS的发现之一，基因组学的治疗抵抗型精神病(GTRP)研究。GTRP将对1,000名患有难治性精神病(TRP)的住院患者进行完整的外显子组测序(WES)。GTRP的目标是识别与TRP相关的基因组变异，并确定从这些基因组测试中是否出现了任何临床上可操作的信息，这些信息可能有助于改善特定患者参与者的精神卫生保健。我建议研究GTRP的经验，以解决三个研究目标，这三个研究目标对于理解严重精神病患者在翻译精神病学基因组研究中面临的挑战至关重要。目标1将是项目的指导研究阶段，目标2和目标3将是独立研究阶段。目的1a采用人种学的参与者观察法和访谈法，研究GTRP研究人员在设计和实施WES同意过程和其研究的结果返回(ROR)部分时影响决策过程的因素。目的1b使用伦理分析来评估GTRP研究的设计，包括WES同意程序和ROR部分。Aim 1c使用法律和政策分析来检查目前存在的监管框架，以保护参与翻译精神病学WES研究的住院重症精神病患者。目标2a是一项由目标1提供信息的经验性考试，采用访谈方法研究GTRP患者参与者、患者参与者的法定监护人或授权代表(LG/AR)、患者参与者的心理健康临床医生以及将开展GTRP的精神卫生机构的官员的观点和偏好。访谈将评估他们对如何处理WES同意程序、选择要返回的结果、ROR同意程序、实际ROR程序以及WES结果的ROR后管理的看法。目标2b使用法律分析来检查LG/AR、临床医生和精神卫生机构在研究人员返回WES结果后对这些结果的管理承担何种法律责任(后ROR管理)。目的3使用伦理和法律分析来探索应用法律信托关系模型(FRM)的含义，以定义在翻译精神病学基因组研究中不同各方对患者参与者所承担的伦理责任。这项工作将由目标1和目标2中收集的数据提供信息。