|Title||Whole-genome sequencing as an investigational device for return of hereditary disease risk and pharmacogenomic results as part of the All of Us Research Program.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Venner, E, Muzny, DM, Smith, JD, Walker, K, Neben, CL, Lockwood, CM, Empey, PE, Metcalf, GA, Kachulis, C, Mian, S, Musick, A, Rehm, HL, Harrison, S, Gabriel, S, Gibbs, RA, Nickerson, D, Zhou, AY, Doheny, K, Ozenberger, B, Topper, SE, Lennon, NJ|
|Corporate Authors||All of Us Research Program Regulatory Working Group|
|Date Published||2022 Mar 28|
|Keywords||Genomics, Humans, Pharmacogenetics, Population Health, United States, Whole Genome Sequencing|
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
|Alternate Journal||Genome Med|
|PubMed Central ID||PMC8962531|
|Grant List||OT2 OD002748 / OD / NIH HHS / United States |
OT2 OD002750 / OD / NIH HHS / United States
OT2 OD002751 / OD / NIH HHS / United States