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.
Journal
Genome medicine
ISSN: 1756-994X
Titre abrégé: Genome Med
Pays: England
ID NLM: 101475844
Informations de publication
Date de publication:
28 03 2022
28 03 2022
Historique:
received:
14
05
2021
accepted:
14
02
2022
entrez:
29
3
2022
pubmed:
30
3
2022
medline:
5
4
2022
Statut:
epublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 35346344
doi: 10.1186/s13073-022-01031-z
pii: 10.1186/s13073-022-01031-z
pmc: PMC8962531
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
34Subventions
Organisme : NIH HHS
ID : OT2 OD002748
Pays : United States
Organisme : NIH HHS
ID : OT2 OD002750
Pays : United States
Organisme : NIH HHS
ID : OT2 OD002751
Pays : United States
Informations de copyright
© 2022. The Author(s).
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