Developing a National Newborn Genomes Program: An Approach Driven by Ethics, Engagement and Co-design

Abstract

The transformative potential of whole genome sequencing (WGS) as a diagnostic tool in healthcare has been demonstrated by initiatives including the 100,000 Genomes Project and is now offered to certain patients in the National Health Service (NHS) in England. Building on these foundations, the utility of WGS in the newborn period can now be explored. Genomics England is working in partnership with NHS England and NHS Improvement and other healthcare, patient and public interest groups to design a research program embedded in the NHS to explore the potential challenges and implications of offering WGS in all newborns. The program will aim to: 1) evaluate the feasibility, utility and impact on the NHS of screening for childhood-onset rare actionable genetic conditions; 2) understand how, with consent, genomic and healthcare data could be used to enable research to develop new diagnostics and treatments; and 3) explore the implications of storing an individual’s genome for use over their lifetime. Recognizing the important practical, scientific and ethical questions that we must explore in dialogue with the public and experts, we are taking a collaborative, evidence-based and ethically deliberate approach to designing the program. An iterative co-design process including a nationwide public dialogue has identified emergent themes and ethical considerations which are the focus of the program’s design. These themes will be further developed through continued engagement with healthcare professionals, researchers, ethics experts, patient groups and the public, with an ongoing commitment to embedding ongoing ethics research and co-design into the delivery of the program.

A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases

“…Feasibility pilots over the last decade found that many of the initial ethical, legal, and social implications (ELSIs) of genomic NBS were not observed in practice. [23][24][25]46,[63][64][65] Many ELSIs are solved by adherence to the original criteria for NBS disorder selection and requiring informed parental consent. 31,46 Practical concerns, however, will be how to maintain the current 98% participation in NBS despite a requirement for consent and the allowable secondary use of genomic information.…”

“…[7][8][9][10][11][12][13][14][15][16][17][18][19][20] rWGS is attractive for comprehensive NBS because it concomitantly examines almost all genetic diseases with similar time to result as biochemical NBS of DBSs by mass spectrometry (NBS-MS). [21][22][23][24][25] Here, we describe adaptation of Dx-rWGS methods for comprehensive NBS (NBS-rWGS). We detail scalable, feedbackinformed methods for newborn screening, diagnosis, and virtual, acute management guidance for 388 diseases with effective treatments and report analytic performance and clinical utility in large retrospective datasets.…”

Dispatches from Biotech beginning BeginNGS: Rapid newborn genome sequencing to end the diagnostic and therapeutic odyssey

“…For primary immunodeficiencies and DMD, genomic testing is required in NBS-positive subjects to define the specific genetic disorder, and, thereby, appropriate specific treatments. Secondly, there is now greater governmental attention to the unmet burden of childhood orphan genetic diseases, leading to large government funded NBS by genomic sequencing efforts in the United Kingdom, the European Union, and Qatar (Bick et al, 2022;Hopkins, Kinsella, & Evans, 2021;Mbarek et al, 2022;Pichini et al, 2022). Thirdly, there is now a large literature regarding the ELSI of NBS by genomic sequencing, as evidenced by an issue of the Hastings Center Report (Johnston et al, 2018).…”

Whole genome sequencing for newborns—The devil is in the details

“…One of the places that may uncover answers to these and many other questions likely will be from a pilot National Newborn Genomes Program that Genomics England, in partnership with the National Health Service, is launching in 2023. 8 This study is uniquely positioned to address the effects of newborn genome sequencing on a national scale and includes research into aspects such as feasibility, consent procedures, use of data for research in future diagnostics and treatments and the long-term implications of storing and using a genome over an individual's lifetime. As genome sequencing is an extremely private dataset, there is a great need to handle these data correctly with room for stakeholders at the table during the design and pilot phase to ensure that such a programme is rolled out with the full trust and support of the public and with infrastructure and know-how in place.…”

“…At its core is an alignment of expectations of participants and the public. One of the places that may uncover answers to these and many other questions likely will be from a pilot National Newborn Genomes Program that Genomics England, in partnership with the National Health Service, is launching in 2023 8 . This study is uniquely positioned to address the effects of newborn genome sequencing on a national scale and includes research into aspects such as feasibility, consent procedures, use of data for research in future diagnostics and treatments and the long‐term implications of storing and using a genome over an individual's lifetime.…”