Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Genome Med. 2022 Mar 28;14(1):34. doi: 10.1186/s13073-022-01031-z.
The All of Us Research Program (AoURP, "the program") is an initiative, sponsored by the National Institutes of Health (NIH), that aims to enroll one million people (or more) across the USA. Through repeated engagement of participants, a research resource is being created to enable a variety of future observational and interventional studies. The program has also committed to genomic data generation and returning important health-related information to participants.
Whole-genome sequencing (WGS), variant calling processes, data interpretation, and return-of-results procedures had to be created and receive an Investigational Device Exemption (IDE) from the United States Food and Drug Administration (FDA). The performance of the entire workflow was assessed through the largest known cross-center, WGS-based, validation activity that was refined iteratively through interactions with the FDA over many months.
The accuracy and precision of the WGS process as a device for the return of certain health-related genomic results was determined to be sufficient, and an IDE was granted.
We present here both the process of navigating the IDE application process with the FDA and the results of the validation study as a guide to future projects which may need to follow a similar path. Changes to the program in the future will be covered in supplementary submissions to the IDE and will support additional variant classes, sample types, and any expansion to the reportable regions.
美国“全民研究计划”（AoURP，“该计划”）是由美国国立卫生研究院（NIH）发起的一项倡议，旨在招募全美 100 万人（或更多）参与。通过参与者的反复参与，正在创建一个研究资源，以支持各种未来的观察性和干预性研究。该计划还承诺生成基因组数据，并向参与者返还与健康相关的重要信息。
全基因组测序（WGS）、变异调用流程、数据解释和结果返还程序必须经过创建，并获得美国食品和药物管理局（FDA）的调查性器械豁免（IDE）。整个工作流程的性能是通过最大的已知跨中心、基于 WGS 的验证活动来评估的，该活动通过与 FDA 的多次互动，经过数月的迭代进行了改进。
WGS 过程作为返回某些与健康相关的基因组结果的设备的准确性和精密度被确定为足够的，并获得了 IDE。
我们在这里介绍与 FDA 一起进行 IDE 申请流程的过程以及验证研究的结果，作为未来可能需要遵循类似路径的项目的指南。未来对该计划的更改将在 IDE 的补充提交中涵盖，并将支持额外的变异类别、样本类型以及报告区域的任何扩展。
