The PHG Foundation welcomes this announcement, which accords with much of the vision for using whole genome sequencing in clinical practice that we described in our document Next Steps in the Sequence. The strategy is a very positive development in support of the objectives of global leadership in healthcare genomics and improving health services for NHS patients. The extra resources committed to basic and translational research will act as powerful drivers. In addition, the commitment to build a sustainable multi-sector infrastructure including data linkage to support these activities is vital to future success.
The provision of 100,000 Whole Genome Sequences (WGS) for NHS patients is an important opportunity. These will be of diagnostic quality and will be provided in the next 3-5 years. The initial focus will be on cancer, rare diseases and infectious diseases. Service design for this provision will take place in 2013 and procurement in 2014. This is a very positive development in promoting additional NHS diagnostic capacity, but several questions remain.
The strategy acknowledges that there is much still to be done to make this operational. Sequencing the genome at a cost and speed that allows feasible introduction into routine healthcare is a technological triumph. But it is only part of the challenge.
Most importantly the PHG Foundation notes that NHS preventive and healthcare services must be made ready to receive and embed genomic science. Such readiness has both political and practical dimensions. It is, from a political perspective, unfortunate that, although there is a general commitment to support innovation and translation of scientific developments into benefits for patients there is no, or little, specific mention of genomics within documents published in recent months from the Department of Health, Public Health England or the NHS Commissioning Board. This provides a stark contrast with the high prominence given to genomics in the Life Sciences Strategy published in 2011, and the Strategy for UK Life Sciences One Year On published this Monday. In the current economic climate, where difficult prioritisation decisions have to be made, significant national leadership will be required to ensure that those with responsibilities for commissioning and providing disease prevention, diagnosis and treatment services in the NHS do afford genomics the necessary priority. We believe that it is vital that Government strategy is ‘joined up’; otherwise access to genomic medicine may remain limited to those within easy reach of teaching hospitals and centres of research excellence.
On the practical side we must also work out a number of implementation issues such as when to use genomic testing, how to interpret genomic data and how these data can be used to improve health outcomes or prevent disease in a systematic way across the NHS. This will require a commitment that parallels the scientific work in scale and timing. The continued involvement of regional genetics centres (whether or not they are providing sequencing tests), the UK Genetic Testing Network and clinicians from many other areas of medicine and primary care as important stakeholders, will be vital to implementation. The expertise of clinical geneticists should be embraced while, at the same time, promoting the use of genomics in mainstream medicine, through engagement with professional organisations such as the Royal College of Physicians, the NHS Commissioning Board and Public Health England and, through them to local commissioning organisations. The Academic Health Science Networks will also have an important role to play in coordinating the work of universities, healthcare services, the voluntary sector and industry at both local and national levels. These less glamorous, and more distributed aspects of scientific development and translation must also be recognised and appropriately funded if this initiative is to achieve its full potential.
The PHG Foundation identifies practical elements of implementation work and the wider policy implications, both of which will be vital. We note the importance of using genomic data to improve patient outcomes. This should include prevention and enhanced treatment outcomes for diagnosed disease and requires assessment of clinical utility, effectiveness and cost effectiveness in clinical practice. The relative paucity of professionals, particularly health economists, able to undertake such assessments will be a barrier.
The commitment to improving bioinformatics infrastructure is very helpful. The strategy rightly acknowledges the importance of interpretation and the need to build large population datasets in which genotypic and detailed phenotypic elements are associated whilst maintaining appropriate safeguards for confidentiality and privacy. We believe that the Deciphering Developmental Disorders (DDD) project provides a prototype. To fully utilise the opportunity from the proposed sequencing of 100,000 genomes in a similar way for other rare disorders, it will be necessary to make significant investment in expert work to define agreed/standardised rare inherited phenotypes in clinical areas such as cardiovascular or renal medicine, neurology, ophthalmology and endocrinology and to enable NHS clinicians and scientists to input accurate data and use testing accordingly. Interpretation of such information for clinical purposes will require the on-going development of bioinformatics systems with evidence-based algorithms to facilitate clinical decision-making. We believe that this is a major undertaking that will require significant investment on the NHS side as well as in research.
We must be sure that we use these whole genome tests wisely and with a focus on patient benefit. It is all very well to sequence genomes in research or clinical settings but we must know what will be done with the information so obtained. The PHG Foundation programme Realising Genomics in Clinical Practice will explore many of these issues. As such testing begins to be used in a clinical setting, this will require all stakeholders to agree the scope of whole genome sequencing and develop consensus on how and when it should be used. There will be requirement for guidelines on what genomic information will be deliberately sought and what other information may also inadvertently be revealed and how these will be managed. Finally, the opportunity to deliberately seek other genomic information, such as carrier status or susceptibility to an unrelated late onset disease, as the basis of individualised preventative health initiatives, should receive serious consideration. Most particularly, there will be requirement for multidisciplinary assessment of evidence of benefits against the obligation to protect patients from possible harm from such ‘opportunistic’ screening.
Finally, there are many detailed areas that will require clarification before work on the 100,000 genomes goes ahead. These include: the nature of ‘full and explicit consent’ that patients will need to give before their genetic data are analysed and stored. What happens if they change their minds and what information related to their clinical conditions or otherwise will be provided to them? How will the implications of findings for other family members be handled? What secondary use of data may be allowed and how will public concern related, for example, to insurance or forensic use, be managed? How will public trust in the NHS be maintained in the light of possible commercial gain from the use of valuable data obtained from public services?
The Government announcements in Strategy for UK Life Sciences One Year On are an expression of confidence that genomic science will deliver major boosts to health and to the UK economy. Over the forthcoming months and years the PHG Foundation aims, through its own work programme and in collaboration with key stakeholders, to help steer this investment in directions that will deliver benefits to UK patients and the wider health system.
The PHG Foundation in its comment on the Strategy for UK Life Sciences Update drew attention to the need to engage in a much greater way than hitherto with the NHS and the mechanisms for the delivery of healthcare in the UK. The Ministerial Statement of the Secretary of State for Health published on Monday, announcing that the NHS Commissioning Board would “lead on a delivery framework and service design with an aim to have contracts in place by April 2014 at the latest” is therefore very much welcomed. The mechanisms described in Innovation Health and Wealth. Accelerating Adoption and Diffusion in the NHS, updated on the same day, will also do much to hasten the implementation of the genomics agenda, particularly with its commitment “to embed Innovation Health and Wealth at the heart of the NHS Commissioning Board and the new NHS Architecture” and to establish Academic Health Science Networks across the country.
These initiatives, however, appear to have forgotten the impact of genomics on public health programmes, which can be effected not just through the delivery of health services, but across the other two of its three areas of practice, health improvement and health protection.The UK is already starting to engage with programmes to improve the education of the NHS workforce and with improving the utility and efficiency of research. NICE, through its diagnostic programme, is starting to engage across a range of predictive and diagnostic technologies, while the UK Genetic Testing Network has shown itself to be a world leader in genetic test evaluation.
The involvement of the public health workforce in these exciting developments has, by contrast, been almost non-existent.The recent moves of most public heath practitioners to local authorities will not have aided this genomics agenda. The PHG Foundation apart, there has been next to no interest in the role of genetics and genomics in public health, not by public health colleagues nor by the Faculty of Public Health. We cannot therefore be too strong in urging that in the same way that the NHS Commissioning Board will now be integrally engaged in the impact of genomic science on health service provision, Public Health England will need to take these developments within the central core of their thinking, and the Faculty of Public Health will also need to engage.
The Office of Public Health Genomics at the Centers for Disease Control and Prevention (CDC) has recently identified three priorities for action by public health practitioners. First, "to serve as an honest broker for emerging genomic applications to consumers, providers and policy makers to inform what is ready and what is not". Second, "to implement evidence based genomics applications and discourage use of unvalidated applications". Third, "to evaluate the impact of public health interventions to assess benefits and harms for subsets of the population based on genetic and genomic information" . These priorities have been at the heart of the work of the PHG Foundation for some years now, but they need now to be embraced by Public Health England and by the Faculty.
A significant part of this future agenda will be around what has been variously termed personalised or stratified medicine, the idea that interventions, both clinical and public health, might be more efficiently directed at subgroups of the population rather than across the whole. Public health practitioners must therefore advocate for health policies that can respond responsibly to the personalisation of healthcare by understanding the ethical, legal and social implications of stratification; establish information systems that empower patients, consumers and citizens to take responsibility for their own health; provide to health professionals the evidence base for the efficacy of genome based interventions; ensure the regulation of new technologies that will both encourage innovation yet protect the citizen; and work more closely with industry in the fields of diagnostics, devices and medicines for the benefit of the population’s health.
The field of infectious diseases has started to be revolutionised by the ability to sequence quickly and cheaply a range of pathogens; in time this will be supplemented by a better understanding of host susceptibility. In the very near future it is anticipated that sequencing will be used for certain diagnostics, local infection control, outbreak identification and analysis and in some cases (such as some cases of tuberculosis) to determine antibiotic susceptibilities.
Similarly, the public health domain of screening programmes will need to be reexamined in the light of greater understanding of the molecular basis (and hence heterogeneity) of diseases - both rare and common; and the emerging ability to use genomic and other biomarkers to stratify risk for common diseases such as breast cancer or heart disease and to fine-tune screening programmes accordingly. Genomic sequencing such as that announced in the Strategy for UK Life Sciences update would support an increasing shift towards personalised lifetime prevention based on knowledge of disease susceptibility and risk for heritable disorders in individuals and their offspring. These are new areas with which public health professionals, with their detailed knowledge of prevention from a population perspective, must engage.
The involvement of public health professionals in the commissioning process has been a strength of the UK system of commissioning healthcare over many years. At no other time in its history will that be more needed.Individuals who understand the science and can objectively evaluate it and give objective advice to commissioners (the 'honest broker' role) will be essential. The recent changes in the organisation of public health has made this more difficult but Public Health England with the Commissioning Board must ensure that this input will continue to be available through individuals who understand both genomic science and the principles of population health. The PHG Foundation has in the past suggested that there should be a Consultant in Public Health with special understanding and expertise in genomics and molecular science for every 5 to 8 million population, to provide input into commissioning. The training of 8 to 12 such individuals over the next two to three years to provide this function would appear to us to be an urgent task.
The UK Government has recognised the importance of genomic science to both healthcare and the UK economy. Public health organisations must now do the same. They must ensure that their preoccupation with social models of disease are complemented by a similar understanding of biological determinants, and understand that the two approaches are complementary and necessary for the improvement and protection of population health.