Ethical Approaches to Genotype-Driven Research Recruitment

基因型驱动的研究招募的道德方法

• 批准号: 7945361
• 负责人: LAURA M. BESKOW
• 金额: $ 41.51万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7945361
• 关键词: Address; Area; Attention; Bioethics; Chills; Clinical and Translational Science Awards; Collection; Complex; Consent; Data; Data Set; Databases; Deception; Development; Diagnosis; Disease; Educational workshop; Equilibrium; Ethical Issues; Ethics; Follow-Up Studies; Future; Genetic; Genetic Variation; Genomics; Genotype; Goals; Guidelines; Hand; Human Genetics; Individual; Institution; Internet; Interview; Link; Outcome; Participant; Pathway interactions; Perception; Phenotype; Policies; Population; Process; Protocols documentation; Reaction; Recommendation; Recontacts; Recruitment Activity; Research; Research Ethics Committees; Research Personnel; Review Literature; Risk Reduction; Role; Site; Structure; Surveys; Translations; Variant; base; case control; database of Genotypes and Phenotypes; design; evidence based guidelines; experience; genome wide association study; human subject; improved; interest; novel; population based; programs; prospective; public health relevance; tool; trait

DESCRIPTION (provided by applicant): Ethical Approaches to Genotype-Driven Research Recruitment This application addresses broad Challenge Area (02) Bioethics and specific Challenge Topic, 02-RR-101* "Recontact Issues in Genotype and Genome-Wide Association Studies." Many genotype and genome-wide association studies (GWAS) are conducted using a phenotype-driven approach: cases and controls are identified based on the presence or absence of a particular condition and analyses are undertaken to identify gene variants associated with that condition. The inverse-a genotype- driven approach-is receiving increasing attention as another powerful tool for understanding the impact of genetic variation. Cases and controls are defined among existing study populations based on the presence or absence of a particular genotype, and in-depth phenotyping is then conducted to understand the relationship between observable traits and the gene variant of interest. Enabling such a "bottom-up" approach to identifying and recruiting participants for follow-up studies could significantly advance the pace of genomic research by expanding the existing mechanisms for studying the functional significance of human genetic variation. Such approaches, however, present ethical challenges that have not been fully addressed. Genotype-driven recruitment is inextricably linked to the complex and much-debated issue of disclosing individual research results: when individuals are recontacted, what if anything should they be told about the genotype that led to their being recontacted? There is a fundamental tension between avoiding the introduction of potentially unwanted and uncertain information, and avoiding deception when explaining to prospective participants the purposes of the research and why they are being approached for participation. The purpose of this project is to develop evidence-based guidelines for addressing the ethical issues that arise in genotype-driven recontact and research recruitment. Specifically, this project involves 3 Clinical and Translational Science Award (CTSA) sites that will collaborate to: Explore the perceptions of research participants who have experienced genotype-driven recontact for further research participation. Investigate IRB chairs' experiences, opinions, and concerns about genotype-driven recontact and research recruitment. Formulate guidelines to assist IRBs and researchers in identifying balanced approaches to genotype-driven recontact and research recruitment. This proposal addresses 2 significant challenges: (a) the collection of empirical data on the novel concerns posed by genotype-driven recontact and recruitment; (b) the translation of such data into guidelines to assist researchers and IRBs. The results of our projects will be disseminated widely through a variety of mechanisms, including the CTSA Consortium. To sustain further progress on these complex issues, our proposal includes a plan to build a robust program of future research utilizing existing research networks to assess our guidelines with respect to stakeholder reactions, as well as implementation and outcomes. PUBLIC HEALTH RELEVANCE Genotype-driven approaches to identifying and recruiting participants in existing studies for follow-up research could significantly advance the pace of genomic discovery, thus helping to achieve the ultimate goal of enriched understanding of the role of genetic factors in common, complex diseases and improved pathways to risk reduction, diagnosis, and treatment. Recontacting research participants about additional studies based on genotype, however, involves ethical concerns that arise throughout the research process: during recruitment and consent for the original study, during the recontact process itself, and during recruitment and consent for the follow-up study. We propose to address these challenges through the collection of empirical data from multiple stakeholders about genotype-driven recontact and recruitment, and the development of evidence- based guidelines that provide appropriate protections for research participants, yet avoid overly restrictive policies that have a chilling effect on research and limit opportunities for those who would like to participate.

描述(由申请人提供)： 本申请涉及广泛的挑战领域(02)生物伦理学和具体的挑战主题，02-RR-101*“基因类型和全基因组关联研究中的重新联系问题”。许多基因和全基因组关联研究(GWAS)是使用表型驱动的方法进行的：根据特定疾病的存在或不存在来确定病例和对照，并进行分析以确定与该疾病相关的基因变异。反转--一种由基因决定的方法--正受到越来越多的关注，因为它是理解遗传变异影响的另一个强有力的工具。在现有的研究人群中，根据特定基因的存在与否来定义病例和对照，然后进行深入的表型分析，以了解可观察到的特征和感兴趣的基因变体之间的关系。采用这种“自下而上”的方法来确定和招募参与者进行后续研究，可以通过扩展现有机制来研究人类基因变异的功能意义，从而显著加快基因组研究的步伐。然而，这些方法带来了尚未完全解决的伦理挑战。由基因决定的招聘与披露个人研究结果这一复杂且备受争议的问题有着千丝万缕的联系：当个人被重新联系时，如果他们应该被告知导致他们再次联系的基因的话，那该怎么办？在避免引入潜在的不必要和不确定的信息，以及在向潜在参与者解释研究的目的和为什么与他们接触参与时避免欺骗之间存在根本的紧张关系。这个项目的目的是制定基于证据的指导方针，以解决由基因型驱动的再联系和研究招募中出现的伦理问题。具体地说，该项目涉及三个临床和转化科学奖(CTSA)网站，它们将合作：探索经历过因基因型驱动的重新联系以进一步参与研究的研究参与者的看法。调查IRB主席对基因驱动的再联系和研究招募的经验、意见和担忧。制定指导方针，协助IRBs和研究人员确定以基因为导向的再联系和研究招募的平衡方法。这项建议解决了两个重大挑战：(A)收集关于由基因驱动的重新联系和招募带来的新问题的经验数据；(B)将这种数据转化为指导方针，以帮助研究人员和IRBs。我们项目的成果将通过包括CTSA联盟在内的各种机制广泛传播。为了保持在这些复杂问题上的进一步进展，我们的建议包括一项计划，利用现有的研究网络来评估我们关于利益相关者反应以及实施和结果的指导方针，以建立一个强大的未来研究计划。 公共卫生相关性--在现有研究中确定和招募参与者进行后续研究的基因类型驱动的方法可以显著加快基因组发现的步伐，从而有助于实现最终目标，即丰富对遗传因素在常见、复杂疾病中的作用的理解，并改善降低风险、诊断和治疗的途径。然而，重新联系研究参与者关于基于基因型的额外研究涉及整个研究过程中出现的伦理问题：在招募和同意原始研究期间，在重新联系过程本身，以及在招募和同意后续研究期间。我们建议通过从多个利益相关者那里收集关于基因型驱动的重新联系和招募的经验数据，并制定基于证据的指南来应对这些挑战，这些指南为研究参与者提供适当的保护，同时避免过度限制性的政策，这些政策对研究产生寒蝉效应，限制了愿意参与的人的机会。