The Newborn Genomes Programme: Genomics England answers your questions

At the recent Progress Educational Trust event 'Whole Genome Sequencing at Birth: Workforce Implications for Healthcare Professionals and Beyond' (a film of which can be watched on BioNews), there were many more questions from attendees than could be addressed by speakers during the allotted time.

Genomics England agreed to provide written responses to some of the questions submitted by attendees. These questions, and Genomics England's responses, are given below.

Genomics England is currently seeking views on the principles that might inform its choice of conditions to be looked for, in newborn babies whose whole genomes are sequenced as part of the Newborn Genomes Programme research pilot. Please submit your own views by completing this survey (the survey will close on 14 June).

1. How do we ensure the NHS healthcare workforce is in place before whole genome sequencing (WGS) at birth programme moves ahead?

   We know that workforce issues are right at the top of key issues to understand and address before any family is recruited to the programme. Our public dialogue participants recognised and highlighted this to us right at the beginning of our work. We have dedicated working groups looking at workforce, training and education issues. We're speaking to workforce representatives and groups, and making sure we're putting the right structures and processes in place to support families across the whole journey.

2. Will the current staffing levels and workload within the NHS be sufficient when there isn't currently enough time to train new scientists, particularly with limited training places available each year?

   We recognise the intense pressure the NHS is under, and the workforce and resource issues that come with this. One of the reasons this research programme is 'NHS-embedded' is that we are not just gathering evidence on the clinical and scientific aspects of using WGS in newborns, but on the likely impact of what resources a future service may need – if indeed it can be demonstrated that such a service is the right thing to do. We're working with organisations including NHS England, Health Education England and Royal Colleges, and involving those that have experience of workforce issues in the NHS – such as Sarah-Jane Marsh, chief executive of Birmingham Women's and Children's NHS Trust, who chairs our Steering Group.

3. Upskilling the existing force is really important to include genomics, good clinical practice and research-specific skills.

   We're taking the time to carefully consider what education and training is required by all of the different professional groups that will be involved in this programme. We're working closely with Health Education England and the Genomics Education Programme to develop competency frameworks and training resources, building on existing resources, that will ensure that the workforce is equipped to deliver this research programme.

4. Could the analysis of individual variants by specialist teams with knowledge of the individual genes be implemented? Analysis is currently being performed widely by scientists with less experience of consequences of variants in specific genes which makes classification of variants difficult.

   We are engaging with clinical scientists and NHS Genomic Laboratory Hubs to explore how the variant analysis process will work in the research programme, and will continue to work closely with this important group. We've also already had conversations with over 100 paediatric specialists in the NHS about how best to deliver quick and effective care to children and their families who test positive for the conditions that the programme will look for.

   It's worth noting that, because these conditions are rare, we might only expect 500-1000 babies out of the 100,000 who have WGS to test positive, and so in each specialist area there may only be two to three babies identified in each year of the research pilot. It's also worth remembering that these babies already have the condition – they will be coming to the NHS for treatment at some point in their early lives, and so the conversations focus on what benefit spotting these babies earlier will be, and how we can make sure there is the right treatment and care pathway in place before the programme begins.

5. It currently takes 15-30 minutes to complete the current paperwork required for WGS. Will the newborn WGS programme result be made available to clinical teams if a newborn presents with health problems or will they have to complete the current standard of care test paperwork?

   We are looking carefully at the systems we need to have in place. This includes looking at how, if a baby's genome has been sequenced at birth, their sequence data might be made available to clinical teams in the future to provide clinical support should a child present later on in childhood with medical problems.

6. Will carriers of the conditions being screened for also be reported, and will the consent of both parents be required?

   We still have work to do to understand what conditions, genes and variants would be included in the pilot programme – so it's a bit early to have a complete answer as to what the process might be. However, it's most likely to be the case that further tests would be needed if a child is found to have a significant variant from WGS; this would likely include biochemical testing and further genetic analysis. It may then be appropriate to obtain samples from parents for testing. We are working with genetic counsellors and other professionals who already deal with these kinds of issues to make sure that the right training and support is provided.

7. After two years of the COVID pandemic, NHS services are already struggling to implement WGS testing in diagnostic settings. Do you think it is sustainable to launch this pilot now, considering the amount of resources it will need?

   We absolutely recognise the severe pressure that the NHS currently is under due to the pandemic. And we also know that WGS testing is not yet uniform across the country. But we have an opportunity in this research programme to explore whether or not identifying children with treatable conditions early would save some of the time and cost currently involved in investigating, reviewing and diagnosing children once they have already presented with symptoms or illness. It's also worth pointing out that the funding for this programme is coming from central research sources, and is not being taken from routine service budgets.

8. Will all Genomic Laboratory Hubs (GLHs) be implementing the WGS programme?

   There have been no decisions made yet on how the WGS sequencing will be undertaken, or who will do it. We're taking the time to make an informed decision on the best way that this will work.

9. Given the very significant challenges, what is the time frame for the pilot and then implementation?

   We plan to begin recruiting families to the research pilot in mid-2023, providing that the systems, resources, and support are in place. It is likely to run for two to three years, and once we have the data, there will be a period of evaluation and analysis before decisions are made (not by Genomics England) about whether, where, and how to use WGS in this context.

10. Initiatives like this hold great promise but unfortunately fail to include robust measures to be inclusive to many communities within our population. How will these points be factored in and addressed before implementation?

    We know that we need to proactively make efforts to ensure that underserved communities in the UK aren't further disadvantaged – and this is part of our planning, including for example in the choice of pilot sites. At Genomics England, our Diverse Data initiative aims to reduce health inequalities and improve patient outcomes within genomic medicine – and we are working closely with the team on developing engagement and insights to make sure that this initiative is inclusive as it can be.

11. Who will interpret variants and do we have a robust preventative pathway?

    We are still working on the detail around sequencing and interpretation – but we know that the full pathway from initial conversation to treatment pathway needs to be clear and resourced before we begin. Please also see answer to question 4 regarding our engagement with clinical scientists and paediatric specialists.

12. Timely and widely available next-generation sequencing for symptomatic children should be prioritised, which is currently not universal in UK.

    This is an important point and we continue to work with NHS England through the Genomic Medicine Service and in development and roll-out of the Rare Disease Strategy to achieve this.

13. How will genetic counselling fit in with the future of the NHS, both in terms of potential newborn sequencing and also the wider mainstreaming of genomics?

    As healthcare professionals with specialist training and experience in genomics and the impact on individuals and families, genetic counsellors are integral to the success of mainstreaming genomic medicine. Our public dialogue participants highlighted that genetic counselling must be made available for newborns and families who receive a diagnosis, and we are working with genetic counsellors to incorporate their expertise as we design this research programme. The UK Association of Genetic Nurses and Counsellors have produced a statement about the role of genetic counsellors in mainstreaming genomics.

14. We need huge investment in basic infrastructure across genomic testing in the NHS. Linking up variant interpretation across all GLHs will be invaluable as would a linked laboratory information management system.

    We continue to learn from projects like the 100,000 Genomes Project, both in terms of what worked well and what we could do better, and work with NHS England and other partners to mainstream genomics in the NHS.

15. I understood there would be a limited pilot of around 20,000 trios where some of the hazards and difficulties might manifest and solutions found. I've understood that this is now of much larger size. What numbers are being considered?

    Our current plans are to sequence around 100,000 babies, beginning slowly and carefully to make sure that systems and resources are in place for increasing the volume and ensuring that every family has the right information and support to participate, and that positive results are followed up and every baby put on the right care and treatment pathway. We won't begin the pilot until this is in place.