Ethical Approaches to Genotype-Driven Research Recruitment

描述（由申请人提供）： 伦理方法基因型驱动的研究招聘此应用程序解决了广泛的挑战领域（02）生物伦理学和特定的挑战主题，02-RR-101*“在基因型和全基因组关联研究的重新接触问题。“许多基因型和全基因组关联研究（GWAS）是使用表型驱动的方法进行的：根据特定条件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条件相关的基因变异。反过来，基因型驱动的方法作为理解遗传变异影响的另一个有力工具正受到越来越多的关注。基于特定基因型的存在或不存在，在现有的研究人群中定义病例和对照，然后进行深入的表型分析，以了解可观察到的性状和感兴趣的基因变异之间的关系。启用这种“自下而上”的方法来确定和招募参与者进行后续研究，可以通过扩大现有的机制来研究人类遗传变异的功能意义，从而大大推进基因组研究的步伐。然而，这些方法提出了尚未得到充分解决的道德挑战。基因型驱动的招募与披露个人研究结果这一复杂且备受争议的问题密不可分：当个体再次接触时，如果他们被告知导致他们再次接触的基因型，他们应该被告知什么？在避免引入可能不需要和不确定的信息，以及在向潜在参与者解释研究目的和为什么他们被邀请参与时避免欺骗之间存在根本的紧张关系。该项目的目的是制定循证指南，以解决基因型驱动的再接触和研究招募中出现的伦理问题。具体而言，该项目涉及3个临床和转化科学奖（CTSA）研究中心，它们将合作： 探索经历过基因型驱动的再接触的研究参与者对进一步参与研究的看法。 调查IRB主席对基因型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IRB和研究人员确定基因型驱动的再接触和研究招募的平衡方法。该提案解决了2个重大挑战：（a）收集关于基因型驱动的再接触和招募引起的新问题的经验数据;（B）将这些数据转化为指导方针，以帮助研究人员和IRB。我们的项目成果将通过包括CTSA联盟在内的各种机制广泛传播。为了在这些复杂的问题上保持进一步的进展，我们的提案包括一项计划，利用现有的研究网络建立一个强大的未来研究计划，以评估我们关于利益相关者反应的指导方针，以及实施和结果。 以基因型为驱动的方法来识别和招募现有研究中的参与者进行后续研究，可以显著推进基因组发现的步伐，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，重新通知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：在原始研究的招募和同意过程中，在重新联系过程本身，以及在后续研究的招募和同意过程中。我们建议通过从多个利益相关者收集关于基因型驱动的再接触和招募的经验数据来应对这些挑战，并制定基于证据的指南，为研究参与者提供适当的保护，但避免过度限制性政策，这些政策对研究产生寒蝉效应，并限制那些愿意参与的人的机会。

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.