Ring in genomic medicineFebruary 7, 2020
The GenomeAsia project has demonstrated the potential of large-scale genome sequencing. However, if we are to reap the benefits of such initiatives, there is a need for concerted efforts across the healthcare ecosystem. Just a few years back, genome sequencing was restricted to research laboratories that could afford the cost. Now, genome sequencing has become the talk of the town due to the fact that costs have come down and its integration into clinical practice has started in western countries. The important question to ask at this juncture is: Are our health systems ready for complex, large-volume data and the personalisation of healthcare? Genomic sequencing is a transformative technology and effective only if we integrate into our clinical practices by inducing system-wide changes. This requires us to go beyond the mere technical requirements of establishing sequencing and bioinformatics capacity to process samples. The real barriers are data integration, interpretation, workforce capacity/capability, public acceptability, government engagement, evidence of clinical utility and cost effectiveness.
In countries such as the UK, France, Australia, Turkey and Saudi Arabia, infrastructure and workforce development were conducted together with genetic testing of a large number of patients for rare diseases and cancer, the two important applications of genomic sequencing expected to have immediate clinical benefits. These “proof-of-principle” programmes conducted by governments are driving change and fostering adoption among stakeholders under real-life conditions, while simultaneously gathering evidence for wider implementations. In countries such as the US, Estonia, Denmark, Japan and Qatar, governments have invested in population-based sequencing projects with a return of results to participants. However, the national initiatives in Switzerland, the Netherlands, Brazil and Finland primarily focus on the development of infrastructure, such as common standards and data-sharing policies and platforms.
In the UK, the National Health Services established Genomics England (GEL) in 2013 with a mandate to sequence 100,000 genomes from patients with over 100 rare diseases and seven common cancers. GEL has established centralized infrastructure for the delivery of diagnostic whole-genome sequencing (WGS) services. In France, where the healthcare system is dependent on government-funded national health insurance, the French Plan for Genomic Medicine 2025 was commissioned. It aims to integrate genomic medicine into healthcare by establishing national genomic-medicine industry. In Australia, the national health system is the major stakeholder, but clinical and laboratory genetics services are funded by the six state and two territory governments. Thereby, a “federal” approach was implemented to enable genomic medicine with the engagement of state and federal governments in the development of a National Health Genomics Policy Framework.
A network of 78 organizations, including diagnostic laboratories, clinical genetic service organizations and hospitals, established Australian Genomics in 2014 as a research partnership. This consortium has four programmes: (a) national diagnostic and research network; (b) national approach to data federation and analysis; (c) evaluation, policy, and ethics; and (d) workforce and education. Using experimental learning methodology, over 40 flagship projects across rare diseases and cancer at 30 clinical sites have been started to prospectively evaluate diagnostic and clinical utility, cost effectiveness and new approaches to service delivery. They will also help in comparing different sequencing modalities, including WGS, whole-exome sequencing (WES), RNA sequencing, and large capture panels. Even though the sequencing, bioinformatic analysis, data interpretation, reporting and storage remain the responsibility of diagnostic laboratories, Australian Genomics follows Global Alliance for Genomics and Health (GA4GH) standards in developing frameworks for ordering tests, acquiring consent and capturing phenotypes. Patient advocacy groups and policy makers have established Australian Digital Health Agency to integrate genomic test results into electronic health records. There is already evidence that genomic sequencing not only increases diagnostic yield, but can also reduce costs and improve patient management and clinical outcomes.
In the US, there is a mixed private and public healthcare system. The country has invested in genomic-medicine implementation since 2011, starting with the launch of the National Human Genome Research Institute (NHGRI). NHGRI aims to identify barriers to the implementation of genomics in clinical care and to develop solutions and best practices for widespread dissemination. NHGRI is also addressing specific evidence gaps in the clinical delivery of genomic testing, such as the return of secondary findings, inter-laboratory consistency in variant interpretation, integration of genomic resources with electronic records, and sharing implementation and evaluation experience more broadly. The Precision Medicine Initiative, All of Us, established in 2016–2017, has now launched throughout the US. All of US is engaging 1,000,000 volunteers of all life stages, health statuses, races and ethnicities, and geographic regions to reflect the human diversity of the US. Mobilizing rich and constantly evolving data—from electronic health records, biospecimens and questionnaires to physical evaluations, sensors, and other technologies—the programme will support research at the intersection of lifestyle, environment and genetics to produce new knowledge and lead to the development of innovative prevention strategies and treatments. Both genotyping and WGS are being evaluated as testing modalities initially.
The above-mentioned implementation methods of genomic-medicine initiatives in high-income countries might not necessarily be applicable to low and middle-income countries. However, a broad implementation will be crucial in building representative population reference datasets, such as the one by GenomeAsia, that improve variant interpretation globally. It will also help in accelerating the discovery of genes associated with diseases. Implementation — by forming a network mode — and data sharing for faster and lower costs can help. It is also important to understand and prioritise diseases by evaluating the economic and social context, which can also help address health priority areas such as host-pathogen interactions in infectious diseases; common monogenic disorders, such as sickle cell disease and thalassemias; and complex conditions, including hypertension, dyslipidemia, diabetes, stroke, and kidney disease. The collaboration and open mindedness of clinicians, along with national initiatives for creating a framework of guidelines, can make initiatives like GenomeAsia successful in integrating into clinical practices.
The author is medical scientist and former director of SGRF, Bangalore