Including Adults with Intellectual Disability in Precision Medicine Research - Project ENGAGE

摘要 精准医学研究（PMR）有可能通过挖掘遗传和非遗传来改变健康 疾病的机制和制定有针对性的预防和治疗。成年人的参与 PMR中的智力残疾为解决他们在健康方面的巨大差距提供了新的机会。然而， 确定他们对PMR的包容和参与的独特需求。尽管 有证据表明，大多数智力残疾的成年人表现出同意能力，精准医学（PM） 研究人员可能会将他们排除在外，在决策过程中无法满足他们的独特需求，或者使用代理 很少有意义的同意。智障成年人同意PMR进一步提高了新的 关注的问题，包括同意的最佳模式，以及如何管理遗传结果的返回， 确保基因组隐私，促进包容和赋权-被认为是成功的关键 PMR。不幸的是，许多PM研究人员感到没有能力做出回应;他们表示希望 目前还没有的教育和实践资源。这些差距导致成年人 对智力残疾的研究不足，并对产生知识以解决其健康问题造成障碍 需求它们还阻碍了赋权，在道德上越来越受到质疑： 残疾人希望被纳入PMR。拟议的研究采用了学术界和社区的伙伴关系， 通过以下方式缩小这些差距：（1）对智障成年人进行一项全国性的、针对残疾人的调查， 确定有关决策角色、结果交流、基因组隐私的偏好，以及 参与PMR;（2）创建PMR研究适应性同意工具包，以支持PM研究人员 包括PMR中有智力残疾的成年人，并通过文本复杂性研究对其进行实证测试， 与智力残疾成年人进行认知访谈，以确保这一人群的理解能力;以及（3） 与PM研究人员一起进行社会有效性研究，以评估工具包的可用性、相关性、可接受性， 和全面性。基于网络的同意PMR工具包将免费提供。我们将传播 我们通过研讨会，网络研讨会，同行评审的出版物和专业演讲的研究结果 会议. PMR激起了人们对一种新的、以科学为基础的、授权的医疗保健模式的希望， 接触到并能够使那些最脆弱和经历巨大健康差距的人受益。这 该项目有可能通过帮助PM研究人员避免偏见的陷阱，维护 社区成员重视的人类主体原则，部署战略以进一步发展和多样化 现有的PMR数据集。随着时间的推移，这项工作将有助于促进PMR的实践， 卫生保健-NIH优先事项。这项研究是第一次多个利益相关者，包括成年人与智力 残疾人将合作使用经验伦理调查，以解决同意和其他挑战，在PMR和 将产生关键的理论和实践见解PMR包括成人智力残疾。

Abstract Precision medicine research (PMR) holds potential to transform health by unearthing genetic and non-genetic mechanisms of disease and developing tailored prevention and treatment. Participation of adults with intellectual disability in PMR offers new opportunities to address their substantial health disparities. Yet efforts to identify their unique needs for inclusion and engagement in PMR have been lacking. Despite evidence that most adults with intellectual disability demonstrate consent capacity, precision medicine (PM) researchers may exclude them, fail to accommodate their unique needs in decision-making, or use proxy consent with little meaningful assent. Consent of adults with intellectual disability to PMR further raises novel concerns, including best models for consent and how to manage the return of genetic results while also assuring genomic privacy and promoting inclusion and empowerment—believed to be critical for successful PMR. Unfortunately, many PM researchers feel ill-equipped to respond; they express desire for educational and practical resources that are not currently available. These gaps contribute to adults with intellectual disability being understudied and create barriers to generating knowledge to address their health needs. They also impede empowerment and are increasingly ethically questionable: adults with intellectual disability want to be included in PMR. The proposed study employs an academic-community partnership to close these gaps by: (1) conducting a national, disability-tailored survey with adults with intellectual disability to identify preferences regarding decision-making role, communication of results, genomic privacy, and needs for engagement in PMR; (2) Creating a PMR study-adaptable consent toolkit to support PM researchers in including adults with intellectual disability in PMR and empirically test it via a text complexity study and cognitive interviews with adults with intellectual disability to ensure understandability to this population; and (3) Conducting a social validity study with PM researchers to assess the toolkit’s usability, relevance, acceptability, and comprehensiveness. The web-based consent to PMR toolkit will be freely available. We will disseminate our findings through workshops, webinars, peer-reviewed publications, and presentations at professional meetings. PMR has stirred hopes for a new, scientifically-based, and empowering healthcare model that reaches, and can benefit, those who are most vulnerable and experience substantial health disparities. This project has the potential to transform PMR by helping PM researchers avoid the pitfalls of bias, uphold principles of human agency valued by community members, deploy strategies to further grow and diversify existing PMR datasets. This work will, over time, help foster practices in PMR that promote equitable healthcare—NIH priorities. This research is the first-time multiple stakeholders including adults with intellectual disability will collaborate to use empirical ethics inquiry to address consent and other challenges in PMR and will yield critical theoretical and practical insights to PMR inclusive of adults with intellectual disability.