Taking Whole Genome Sequencing Mainstream
In our first Front Line Genomics Roundtable discussion, experts from UK healthcare and research discuss what needs to be done at a practical level to integrate genomics into everyday medical practice.
People in the genomics industry are more aware than ever of Next Generation Sequencing technologies, understanding the benefits it will bring and what it could look like when implemented. What is less clear is how to ensure equitable access for all patients, and what support is required for healthcare professionals to provide this?
Genomics England’s 100,000 Genomes Project is the first large-scale project introducing Whole Genome Sequencing (WGS) into the NHS. There is an initiative within the NHS called ‘Mainstreaming’ seeking to bring genomics into the widespread clinical practice. With this in mind, we are asking: What are the barriers to adoption of comprehensive NGS testing in mainstream specialities?
We have gathered people who have been operationally involved with the implementation of the UK’s 100,000 Genome Project, as well as experts who are deeply engaged with the scientific challenges of genomics, to provide their opinions.
On the Panel:
- Richard Durbin (top left), Group Leader of the Human Genetics Programme, Wellcome Trust Sanger Institute, and Global Alliance for Genomics and Health
- Simon Ramsden (top right), Consultant Clinical Scientist, Central Manchester University Hospitals NHS Foundation Trust
- Chaira Bacchelli (bottom left), Head of Experimental and Personalised Medicine Section, UCL Institute of Child Health (London)
- Tom Weaver (bottom right), CEO, Congenica
Simon Ramsden: I think that there are currently two obstacles to wider mainstreaming of genetic testing. The first is the commissioning of tests. Currently tests are commissioned in a wide variety of ways and there is not always money allocated to genetic testing in the budgets of non-genetic medical practitioners. This can pose a barrier, particularly as WGS can be quite expensive. The commissioning of these tests in England is currently being reviewed by NHS England and hopefully this will be resolved in the next couple of years. However Scotland, Wales and Northern Ireland have different commissioning arrangements and it is less clear to me how this will be resolved in the Devolved Nations.
The second barrier is training. Non-genetic specialists are of course very keen to obtain a genetic diagnosis for their patient, however in my experience they are less confident in some of the other aspects of testing such as providing counselling to family members and dealing with secondary findings.
Chiara Bacchelli: To facilitate a transition of genetics into mainstreaming in the NHS, education of the ‘nongeneticist’ clinicians (clinicians of all specialities working outside the world of genetics) is crucial. In my experience of working with such clinicians at Great Ormond Street Hospital (GOSH), I feel there is the need to demystify the belief that the huge amount of data generated by NGS technologies is overwhelming. We need to make them aware that there are user-friendly tools, like Sapientia, that can be used easily by any clinicians to analyse big data. But first, you need to educate them on the basics of genetics and how to interpret such data. The NHS needs to invest in more specialised genome analysts and bioinformaticians as professional figures to be placed in every department across specialities. This requires funding, which could be an obstacle for the NHS, and a change in culture. The 100,000 Genomes Project has massively pushed the boundaries towards mainstreaming, in this sense, also implementing courses to educate healthcare staff.
Although I can see mainstreaming becoming a reality in the future, I am less optimistic about the timeframe of it. I think we are looking at the next generation of clinicians and healthcare professionals. At UCL we are just starting to introduce NGS and data analysis in the undergraduate medical courses curriculum.
The transition will be successful when every speciality in the hospitals has adopted genetic tools and integrated that into their day-to-day practise. I think that will take a few years still.
Tom Weaver: The path leading towards successful introduction of genomic analysis into the mainstream will require advances in 1) automating variant calling and genome annotation at a patient level; 2) simplification of clinical interpretation and reporting workflows; and 3) integration of diagnosis, treatment choice and outcomes with patient electronic health records. Mainstreaming will be introduced in a phased way over several years, and likely vary between therapeutic areas.
Initially, it is likely to require the participation of domain experts contributing to clinical decisions made in multi-disciplinary team (MDT) meetings. The key will be having all the relevant data (including non-genomic data) seamlessly brought together into a single place where it can be interrogated as a whole by the MDT. With time, this information should be fully automated and presented to the non-specialist as a short report and actionable treatment or next step in the patient care pathway.
Richard Durbin: The aim of mainstreaming is to be able to provide clear and useful genetic information to a wider range of medical practitioners than is easily possible via current clinical genetics routes. Because the recipients will not be trained in interpreting primary data, the route to achieve this is to circumscribe more precisely the questions that are being asked and the possible outcomes. For example, a pharmacogenetic test comes under this category, as does ruling out one of a defined set of possible rare genetic causes for a phenotype. The result does not have to be definitive – it is reasonable for one possible outcome to be to refer the collected data to a genetics specialist for further analysis – but equally there needs to be a clear top level indication of what, if anything, was found and what possible next steps if any might be indicated. The barriers to achieving this are to gain agreement of the specific test and analysis work flows for each application, and achieving confidence in the test and its time- and cost-efficacy for busy professionals. The route is to build research and development relationships with leaders in the field, and then crucially with their professional bodies (e.g. Royal Colleges in the UK), with the ultimate measure of success being practitioners not involved in research are using the tests in standard practice.