Coming of Age? Translating Generation into mainstream clinical practice #RocheGenomics #2030Health

Date of Preparation: October 2019 Job number: RXUKCOMM01989j Contents

Acknowledgements 1

Executive Summary 2

Roche in Genomics 3

Foreword 4

Introduction 6

Why does this matter to the UK? 9

Chapter One 10 Accelerating the broad use of advanced genomic profiling

Chapter Two 14 Putting the right structures in place

Chapter Three 20 Securing engagement and trust with patients, the public and the system

Policy Recommendations 23

Conclusion 24

References 26

For more information 28 Coming of Age? Translating Generation Genome into mainstream clinical practice

Acknowledgements

Roche would like to thank the following for taking part in the research, either through an individual interview or attending the roundtable meeting discussion. The report’s content and recommendations are informed by but should not be taken to represent the views of those listed:

Dr Thomas Barlow Professor Jane Maher The recommendations within this report Garvan Institute of Medical Research Macmillan Cancer Support are specific to England, although the principles around ensuring standards and Dr Laura Blackburn Dr Nirupa Murugeasu equity will be equally important for the PHG Foundation Guy’s and St Thomas’ Hospital broader trajectory of genomic medicine Dr Sarion Bowers Professor Sir Munir Pirmohamed across the whole of the UK. Wellcome Sanger Institute University of Liverpool

Dr Hayley Clissold Professor Anna Schuh Wellcome Sanger Institute University of Oxford

Dr Helen Firth Duncan Sim University of Cambridge Cancer Research UK

Dr Tom Fowler Roger Spencer Genomics England The Christie NHS Foundation Trust

Professor Joanne Hackett Dr Jayne Spink Genomics England Genetic Alliance

Dr Steven Hardy Professor Charles Swanton Francis Crick Institute

Jane Hughes Francis Crick Institute

Dr Kevin Litchfield The Francis Crick Institute

Professor Anneke Lucassen University of Southampton

1 Executive Summary

The mainstreaming of genomics in the NHS has As well as the benefits to patients, there are potentially significant benefits to the the potential to be genuinely game changing in economy from investing in genomics. improving patient care. The UK is well placed to become the world leader in genomic medicine. With a vibrant As the frontiers of scientific discovery have moved life sciences industry, heritage in genomics forward, we are now able to explore the genetic drivers research and a single payer healthcare of a person’s disease, and then the possibility of identifying service, the UK has all the necessary ingredients to deliver a first-class national a treatment that has a much higher likelihood of achieving service, and in doing so support the aims a positive response. The fact that some patients are already of the Life Sciences Industrial Strategy. experiencing benefits from this technology demonstrates The NHS in England has begun to 1 how far we have progressed in a short space of time. bring these elements together, first with the 100,000 Project and now the Successful delivery of genomics • We need to move beyond genomics Genomics Medicine Service, making whole won’t just benefit a small number research. Genomic research (including genome sequencing routinely available of patients. It has the potential to ) has provided to certain NHS patients for the first time. extend its reach into almost all rich research insights – drastically But there remains more to do: ensuring aspects of modern medicine – improving how we diagnose rarer diseases. the right funding is available, investing in and when paired with high quality This research must continue as there is expanding and upskilling the workforce, data, it can act as the vanguard still much that we do not know about the and finding a way to ensure equitable to shift services from a ‘one size value of genomics. But at the same time, access across the country without stifling fits all’ approach toward truly we should extend our focus to where innovation. The solution to these cannot be personalised healthcare. genomics research (and the technology delivered by the NHS alone – and the role that underpins it) shows clear clinical of collaborative working with the research Roche undertook primary and secondary benefit for the patient. We are witnessing community, third sector and industry research to better understand what a blurring of the lines between clinical partners must be prominent. was required for genomics to become a genomics and research genomics; and mainstream part of clinical care, looking The NHS Long Term Plan sets out a bold the NHS, regulators and payer bodies specifically at the NHS in England. Our prospectus for improving the health of the must recognise this and adapt accordingly research, presented in this final report, nation over the coming decade. The extent choosing the right genomics technology to finds that: to which genomic medicine is deployed deliver the right outcome at the right time. to help achieve this objective must be the • The introduction of genomics is seismic. • Governments and healthcare systems litmus test for the service in England. It is likely to transform how we currently will face challenging questions. Justifying assess, reimburse and regulate medicines. and articulating the value of data sharing Regulatory and bodies which assess the for both individual and societal benefit value of new treatments need to catch up will require brave policymaking – and to this new reality to ensure the patients refreshing of the social contract between do not lose out on the potential afforded the public and the NHS. Alongside by genomic medicine. this, the UK Government needs to be leading the conversation around ethical challenges posed by genomics; setting clear guidelines for industry involvement, investing in the clinical geneticists, genomic counsellors, bioinformaticians and therapy area expertise that will be required to roll out this technology in an equitable, ethical and proportionate way.

2 Coming of Age? Translating Generation Genome into mainstream clinical practice

Roche in Genomics

Roche is keen to support the successful delivery of genomic medicine in the UK. We are a committed partner for the NHS – investing £388 million in UK R&D in 2017 and registering the third most clinical trials of any company in the same year.2 In 2018, we worked together with NICE and NHS England to ensure eight of our new treatments were made available on the NHS, and we are bringing forward new medicines which can harness genomics for greater patient benefit.

Our vision for How can Roche help deliver personalised healthcare genomics in the NHS? For Roche, genomics is just one element In the UK context, PHC is central to of a broader shift we are witnessing the shift from illness to wellness that is in modern medicine, which we term needed across the NHS, and emerging personalised healthcare (PHC). Roche technologies and techniques are making seeks to bring together new diagnostics, personalisation much more deliverable in advanced data analytics and cutting edge practice. Genomics is one such technology, treatments to drive improvements in and we have an established role as a patient outcomes. PHC is being enabled provider of genomics services. Roche by advances in this technology and, at Foundation Medicine (RFM) services use scale, will unlock significant value for comprehensive genomic profiling (CGP) UK patients and the healthcare system. assays to identify molecular alterations in a patient’s cancer and enables doctors to PHC uses information from a wide match them with relevant targeted therapies, range of data sets and applies advanced immunotherapies and clinical trials. analytics to derive meaningful insights into patients and disease. These insights Our ambition is to support the health can be used to discover, develop and service to ensure genomic testing is deliver highly personalised treatment plans a routine part of NHS care. Roche is that have the potential to significantly establishing a number of partnerships improve patient outcomes. PHC has with NHS organisations, as part of efforts been brought about by an unprecedented from the health service to mainstream convergence of medical knowledge, genomic testing services in England. technology and data science; the likes A focus of these partnerships is to build of which we have not seen before. understanding and experience of CGP among clinicians in the NHS, and ensure that our lifesaving medicines can reach the patients who can benefit most.

3 The science behind As new therapeutic targets are matched with innovative drugs, people with poor the study of how genes Foreword prognosis and metastatic disease are influence the working particularly likely to benefit. The rollout of our bodies and the of the Genomic Medicine Service (GMS) development of illnesses offers a real opportunity to deliver equitable access to genomic testing across has moved on by leaps England, as long as the system is both and bounds over the sufficiently well-resourced and performs last decade – not least well for patients. At Macmillan, we see thanks to the availability huge implications for how these advances will affect how we deliver personalised Professor Jane Maher of next-generation care for people living with cancer. Consultant adviser, Macmillan sequencing. But some concerns remain. Cancer Support As this report highlights, Any system for identifying underlying interactions between conditions must be evidence-based and “Effective partnerships subject to the same criteria as any other individuals and clinicians screening programme. Many tests show between NHS England, are becoming increasingly great promise, but not all the potentially patient groups, cancer informed by a convergence actionable genetic risk scores for cancers of advanced diagnostics are sufficiently precise and consistent registries, research bodies, yet to reliably inform health and care charities and pharma and more high-quality decisions outside a research setting. can ensure a balance data. There are also In addition, support pathways are essential to help people to interpret results. is maintained.” now ambitious targets for expanded molecular Without these, vulnerable people may take measures that are not necessary and/ diagnostic services over or potentially detrimental, in response to the next decade, with the a risk score. Effective partnerships between NHS in England aiming to NHS England, patient groups, cancer “routinely” offer genome registries, research bodies, charities and pharma can ensure a balance is maintained testing to all people with between timely access to innovation cancer “where there is and robust evaluation. clinical benefit”.

4 Coming of Age? Translating Generation Genome into mainstream clinical practice

It’s helpful to remember that some The recent publication of the Topol The GMS is working to map resources “actionable” tests have been available review highlighted a widespread need for patients and ensure information for over 20 years, e.g. for BRCA 1/2 for upskilling the workforce around the is complete and consistent across all mutations, complete with evidenced-based topic of genomics and the associated channels of support. It is creating diagnostic and management pathways data management challenges. There is training and education resources for leading to clinical benefit – yet there is not only the need to increase the number the workforce and working with patients still work to be done to embed their of specialist roles such as genetic to co-produce information materials routine use. There are useful lessons in counsellors, but also a recognition that including those for the consent process. the reports of the early roll-out projects. other members of the health and social It is also working with Health Education Tests were initially very expensive and care workforce will need to be able to England to help upskill existing staff throughput slow, so services were only answer questions that patients may have and support ongoing professional available for those with the highest and support their treatment choices. engagement to enable appropriate likelihood of carrying an actionable Those accessing private genomic testing access to genomic testing. All of these mutation. The cost and timescales have will also require support to understand are vital to produce a service that changed significantly. In 2005, BRCA1/2 and respond to results and their first can deliver high-quality care. testing cost over £1,500 and took six port of call is likely to include online While public and professional months – now it can cost less than £20 resources, GPs and other primary care expectations rise rapidly, much of the and take a matter of days. But while NHS staff, as well as NHS oncologists. work for the GMS to deliver a quality laboratory costs of genetic testing The widespread commercialisation of service is yet to be done. This includes plummeted, dramatic expansion even genomic testing requires a sufficiently developing reliable online information of such well-understood tests was skilled and resourced workforce to and support, upskilling the workforce, restricted by a lack of infrastructure, support patients to understand and finalising consent processes and including the absence of clear respond to the results. supporting sufficient patient engagement commissioned care pathways and staff The increasing availability of genetic to ensure people are well supported. needed to explain complex results, testing offers a further challenge to a The scale of this work should not combined with public distrust in stretched NHS. While there is merit be underestimated. relation to data storage and sharing. in expanding the amount of genetic The latter point is a vital one. It is information available to the NHS and increasingly important to understand other organisations, if the data source “Much of the work the views and concerns of both patients for research is increasingly those for the GMS to deliver and the public around commercialisation who can pay for testing, the lack of of genomic testing, including the ethical representation of those who cannot a quality service is implications of the use and sharing of may lead to further inequality. yet to be done.” associated data, as without this there is a risk that trust in the NHS as a service and as a data handler could be eroded.

Disclaimer Neither this foreword nor this publication constitute the views of Macmillan Cancer Support nor does Macmillan Cancer Support endorse this publication or any product or service of Roche. The foreword is designed to provide information and is not intended to constitute or to be used or relied upon as medical or other professional advice. Macmillan Cancer Support does not accept liability in relation to the use of or reliance upon, nor any errors or omissions contained in, any information contained in this foreword or publication or third-party information included or referred to in either of them.

5 6 Coming of Age? Translating Generation Genome into mainstream clinical practice

Introduction The potential and the pitfalls: Assessing the status of genomic medicine in the UK

Advances in science and technology have rapidly transformed the way healthcare is delivered to patients. Interactions between an individual and their clinician are increasingly informed by a convergence of advanced diagnostics and higher quality data. These give us a clearer picture of a patient’s physiology, enabling the targeting and treatment of diseases in new ways, ultimately achieving better results. Roche refers to these new forms of patient stratification and treatment personalisation as personalised healthcare – a concept at the core of our vision for improving the health of the globe’s population.

Genomics is “It is like a voyage of discovery into unknown not tomorrow. lands, seeking not for It’s here today. new territory but for new knowledge. It should “I believe genomic services appeal to those with a should be available to good sense of adventure.” more patients, whilst Frederick Sanger being a cost-effective Nobel Prize Winner service in the NHS.” for Chemistry, 1980 3 Dame Chief Medical Officer, Generation Genome, 2017 1

7 Introduction

The UK has begun to lay the ground work So how can this ambition set out in for personalised healthcare by adopting the NHS Long Term Plan be realised? Ahead of these important policies and making investments which The formation of the NHS Genomic milestones, Roche took a critical look aim to strengthen data infrastructure, Medicine Service (GMS) has been an at the rollout of genomic medicine protect patient privacy, spur innovation important step on this process as genomic in England, and has developed this and encourage the use of new types of medicine matures in the UK. The GMS report which aims to answer three data within regulatory decision making was launched in Autumn 2018, and seeks fundamental questions: (often referred to as Real World Data). to provide genomic testing through a • What changes are required to single national testing network, One of the key tools in achieving match patients with the right consolidating and formalising existing personalised healthcare is genomics – medicines, so that the insights laboratory provision.6 The Government the study of how genes influence the generated from genomic profiling has now set an objective for the GMS growth, development and workings of can be acted upon and deliver to sequence 500,000 whole genomes our bodies. We have come a long way clinical improvement to NHS by 2023/24, as part of a broader ambition since Frederick Sanger developed some patients as soon as possible? to reach five million genetic tests and of the earliest sequencing technologies analysis over the same timeframe.5 • How can we design the system in the late 1970s. The UK is now an Whilst the formalising of the Genomic in a way that ensures equitable international leader in research in this Laboratory Hubs has been encouraging, access, so that patients can expect field – driven by the 100,000 Genomes there remains more to do to prioritise the same standard of genomic Project which celebrated reaching its the right technology to deliver against testing, irrespective of where sequencing target in December 2018.3 the right objective. they live? With a strong research footing, the UK is well-placed to take this forward by As the Government sets out this wider • How can we bring the public, extending the reach and use of genomics strategy for genomic healthcare, there is patients and people working in into mainstream clinical care. an opportunity for the Government the NHS with us on the journey, to update on the rollout of the GMS, and ensure any possible concerns The NHS Long Term Plan builds and clarify the immediate priorities about genomic data and ethics upon the ambition set out in the Chief for genomics in the UK.7 In particular, are addressed and fundamentally Medical Officer’s landmark 2016 Roche want to see how testing can be build trust in the system? Generation Genome report,4 and has viewed holistically alongside ensuring set the overall ambition for expanded These questions have been explored patients are able to access newer, and more molecular diagnostic services over the by other organisations and groups transformative treatments – whether these next decade, with the NHS able to with an interest in genomics. This are new medicines or existing ones for “routinely offer” genomic testing to report therefore looks to build upon new indications. The next Comprehensive all people with cancer where there existing literature and sets out the Spending Review is also a critical moment is clinical benefit.5 steps required for ‘generation genome’ during which spending outside of the NHS to truly come of age in a way that England budget (such as NHS workforce benefits patients, the NHS and and capital investment) will be finalised broader society. – which could determine the pace of genomic medicine being rolled out.

8 Coming of Age? Translating Generation Genome into mainstream clinical practice

Continued efforts to cultivate and There are other benefits, including Why does this maintain the UK’s leading position in for the UK to retain its reputation for matter to the UK? genomics is also likely to bring a wider innovation in clinical trials. Whilst range of benefits. If the most effective Britain’s departure from the EU brings The expectation forms of genomic testing can be accredited clear challenges, there is also an option and the opportunity and linked to clinical guidelines, they can for the MHRA (which is expected to take inform decisions on patient eligibility on responsibility for the regulation of The introduction of genomic medicine is for targeted treatments – expanding the medicines) to adopt a sensible approach to seismic. For those developing treatments, range of therapeutic options available,10 regulation which balances opportunities it offers possibilities to match these with including from innovative clinical trials. for alignment with those to innovate.12 patients in a way that has not been possible The UK needs to ensure it has the best This will not just benefit the individual before. Previously, we could not predict technology in place to enable further patient receiving a life changing medicine. how they would interact with the biological placement of clinical trials – given the It will also stimulate the growth of the life process in the body – meaning that only increasing role of genomic profiling to science sector in Britain – ensuring one medicine in 5,000 pass clinical trials help stratify patients into clinical studies, it remains one of the best places in the and reach market authorisation.8 Genomics particularly in oncology. There needs to be world to undertake biomedical research.11 presents the opportunity to deepen our widespread use of high quality profiling, TheNHS Long Term Plan makes explicit understanding, allowing us to identify the which is validated for use in clinical trials, mention of this, with NHS England right target for a new treatment based upon as well stratified datasets to assist with confirming it would “play its full part” in an individual’s genomic profile and direct finding trial participants. the recently announced Life Sciences sector our research efforts accordingly. deal.5 There is already a strong basis to Methodology This does not mean we can rely on work from, with a series of organisations In this report Roche sets out a series of genomics to ‘go it alone’. In order for us including Genomics England, the UK practical insights and recommendations to maximise the benefits, we need to see Biobank and leading centres of excellence which have considered how the enormous how this data compares to information such as the potential of genomic medicine can be and symptoms observed about a patient and the Sanger Institute. realised for patients in the NHS. in a clinic – known as phenotyping.9 The The ongoing work to set out a government science of genomics relies upon accurate strategy for genomics should establish a Roche undertook significant primary phenotypic information and when prospectus for the UK as a low risk and research to inform this report. This harnessed together it can form a powerful efficient market for inward genomics included organising one-on-one tool for understanding what drives investment. There is now an opportunity interviews with several experts, and different illnesses and conditions. for the UK to be a pre-eminent leader in subsequently convening a roundtable genomic driven healthcare and research. discussion hosted at the Francis Crick Genomic medicine in the NHS needs Institute in March 2019 to discuss to be focused on areas with most the findings with a wider group of immediate benefit, such as rare diseases stakeholders. The expert insight and cancer. However, in the longer term gained from this was supplemented there is potential for genomics to shape by a review of current policy and how we think about wider issues such external literature. as early detection, prevention and risk, and how society responds to viruses and pathological diseases. Genomics will also probably have other applications which we are not yet aware of.4 Achieving this will require a responsible approach that balances ambition with realism and avoids creating unrealistic expectations with the public.

9 Chapter One Matching patients with the right treatments

“If there is any area that is going to benefit from genomics, it is oncology where we can see the actionability already” 13

10 Coming of Age? Translating Generation Genome into mainstream clinical practice

Chapter One Accelerating the broad use of advanced genomic profiling

Genomic testing provides opportunities to target treatments in a more effective manner and improve patient outcomes. But the sheer scale and breadth of different options available can make it challenging to identify the best routes to accelerate genomic medicine in England. In order for this to be achieved, it will be important to employ a series of core principles. These are:

Have clear guidelines in place Figure 1: The four broad types of genomic testing currently in use which set out the right test at the right time to achieve the Test Description right patient outcome. Scientific advancements have provided Hotspot testing Interrogates mutational “hotspots” in 50-200 cancer us with a repertoire of different genetic (small panel) related genes. and genomic testing technologies – with Test results potentially received in less than seven days. four main types of testing currently in use [see fig 1]. Each of these carry specific advantages and disadvantages – explored Large panel testing Interrogates all genes known to be drivers of tumours. (also known as broad in greater detail in this chapter. Test results potentially received in less that 14 days. panel or comprehensive Alongside appraising different genomic genomic profiling) testing technologies, greater clarity is required around where genomic testing Whole exome Interrogates the coding region (exons) of all genes fits into the current clinical pathway. sequencing (WES) (>20,000 genes). Those interviewed for this report Test results potentially received in weeks. highlighted that the most significant benefit would be derived from an accurate genomic diagnosis as early Whole genome Interrogates non-coding regions (intergenic, in the patient’s journey as possible. sequencing (WGS) repetitive elements and introns) alongside all coding regions (exons).

Test results potentially received in weeks.

11 Chapter One

“Much of the testing is with a treatment as quickly as possible, it and immediate application, but potentially would be sensible to prioritise the profiling misses actionable mutations, by not currently reactive. But in of all those with metastatic cancer, with covering the whole of the gene sequence. a specific focus on tumour types where a the next five years I imagine Broad panel testing, meanwhile, can in targeted therapy has been approved or is some cases offer a goldilocks option – it being mainly used in in the process of being assessed by NICE. homing in on the most clinically important the advanced, metastatic There is already established research genes, and providing a level of information which points to the value of genomic data setting where operating is which can be analysed more quickly than in assisting with the use of personalising in WGS – whilst presenting up to three not an option. We’d like to therapeutic regimens in advanced forms of times as many actionable alterations than the disease (where it is no longer operable) see this delivered via a the most comprehensive ‘hotspot’ tests.18 – particularly breast cancer.16 In the report 13 A broad panel also leaves the option to large panel” Genomics in mainstream clinical pathways, return to the test result at a later date, the PHG Foundation set out some of the should a novel or existing molecule key questions that we must answer at However, views on the appropriate become licenced for treating a mutation different points of the pathway is set criteria for a patient to receive a test where currently there may be no out on the next page [fig 2].14 (and which organisation would establish treatment options available. these) were conflicted. As has been Consider the value of each highlighted elsewhere, there is further test and their application. Several participants in our research uncertainty about which clinician is best emphasised that actionability must be the Whole Genome Sequencing (WGS) placed to make this decision to recommend central consideration when assessing the has provided rich insights for research, a patient for a test, and then analyse the appropriateness of different tests to be particularly within rare diseases. Several results.14 The workforce implications are used in the NHS in England. Some tests participants in our research outlined explored in the context of the Genomic are especially effective in helping clinicians how the use of WGS has reduced the Medicine Service in England in the identify and ‘pair’ patients with treatments. ‘diagnostic odyssey’ that many patients next chapter. Moving forward it is important to ensure experience as they wait years before that clinicians (and those commissioning When it comes to decisions on the right receiving a diagnosis. This point was services) are provided with a range of point in the pathway for genomic testing, emphasised by the patient advocates who different testing options, and then feel NHS England must rapidly arrive at participated in our research, who spoke empowered to adopt the right test for the a consensus to ensure patients do not of the reassurance that many patients right patient outcome at the right time. lose out. In 2014, Cancer Research UK experience when being told of their test estimated that 16,000 patients with non- results – even if this does not result in There is a lot to be excited about in the small cell lung or colorectal cancer did not clinical decisions being taken based mainstreaming of different genomic testing. receive molecular testing, which meant upon this new information. To fully realise the potential this needs to that around 3,500 patients who could have be accompanied by reforms to medicine WGS may not always be the most benefitted from a more targeted medicine regulation and assessment. appropriate test. Research participants did not receive one.15 There is anecdotal explained that other tests, such as large/ As our understanding of disease becomes evidence to suggest that the situation has broad panel testing can deliver more more stratified – with breast cancer now improved since the publication of the immediate and actionable clinical results. characterised as ten different diseases rather Cancer Strategy for England in 2015, but As highlighted by the House of Commons than one – the patient populations receiving as explored in Chapter Two, the lack of Science and Technology Select Committee a treatment are becoming smaller.19 We are central funding for many different forms in its report looking at genomic medicine in a world of ‘malignant snowflakes’ where of testing is hampering progress. in the NHS, WGS at present can bring each tumour is different and requires a Many of those who participated in our additional infrastructure burden compared bespoke response.20 This creates challenges roundtable argued that genomic testing to other tests, with increased storage around recruiting patients to take part in should be introduced as early as possible costs, stricter demands on the collection relevant trials, and thereby demonstrate the into the pathway, as this would therefore of patient samples and is potentially less sufficient evidence required for regulatory present the widest breadth of opportunity sensitive to specific genetic targets.17 The approval and reimbursement. Equally, a for both clinical activity and research. inquiry concluded that there was not yet growing number of medicines will target Given wider resource constraints, research sufficient evidence to demonstrate the genomic mutations rather than where they participants also suggested that it would benefit for routine care, in particular for originate in the body. As such, genomic be important to stratify patients and then common cancers.17 At the other end of the testing will become integral in determining direct testing accordingly. If the primary spectrum, ‘hotspot’ testing delivers clear a patient’s eligibility for a treatment. objective is to link prospective patients

12 Coming of Age? Translating Generation Genome into mainstream clinical practice

Regulators and reimbursement bodies As a guiding principle, our research will need to evaluate how to respond to has concluded that medicines appraisal What recommendations precision medicine. Our research has must evolve to account for evidence from does this section link to? found wide recognition of this looming disparate and new sources, including the Recommendation four challenge from key stakeholders. Moving lifetime or wider benefits that a medicine Reforms to how new medicines are forward, medicines may be more commonly might deliver – and eventually by the assessed, to enable faster access to approved on a conditional basis, with outcome it achieves in practice for the most promising treatments recognition that evidence on its clinical patients.16 This is explored in greater effectiveness will need to be gathered over detail during the policy recommendations Recommendation five time as part of an iterative process. This on page 23. A clear roadmap for the use of will in turn increase the role for real world pooled data in genomic research data (RWD) – with assessment bodies Figure 2: The genomics referral pathway. Recommendation six (such as NICE in England) having to Source: PHG Foundation, 2018 Introduce clear targets for the accept novel clinical endpoints. number of patients to benefit Similarly, the appraisal of new medicines from the new GMS service, currently accounts for the cost of genomic Identifying with a particular focus on cancer testing (as the diagnostic companion). patients Recommendation eleven This is a limitation in the current system NICE should update its approach for health technology assessment (HTA) to the appraisal of precision in England – as such, tests should be medicine molecules provided as part of mainstream clinical Criteria for care in order to comply with the ambitions deciding whom Recommendation twelve set out in the NHS Long Term Plan. Under to test As part of regular agreed reviews, the current HTA design, patients may be NICE should undertake a methods deprived access to the latest treatments assessment in 2020 of how new based on how the genomic test is and emerging genomic technologies characterised and reimbursed. are assessed There is a requirement for the system Who should set to view next generation diagnostic the criteria? tools such as genomics and medicines assessment holistically.

There will always be a tension between ensuring the fastest patient access to Overseeing innovations and maintaining safety application standards and access in an environment of criteria of finite resources. During our roundtable, one attendee raised the challenges around relying on RWD as part of new medicine approvals. It was underlined that RWD Clinical & needs to be supported by clinical trial data, non-clinical and “could not go it alone”. It is clear that factors in the future a mix of different data sets – including both traditional double-blind clinical trials and data from routine care – will be required. Achieving this will require Which clinicians systemic reforms to the current approaches should order of the majority of HTA bodies and how genomic tests health bodies use data more broadly.

13 Chapter Two Making the Genomic Medicine Service work for everyone

Chapter Two Putting the right structures in place

We have considered the potential for new genomic technologies, and where they might sit in the pathway. But how will this interrelate with the NHS in England? As a single payer service, the NHS is held up as a healthcare system well- suited for the rapid update of technological change at scale.

The legacy of the 100,000 Genomes Figure 3: The different elements of the Genomic Medicine Service. Project, along with the establishment Source: NHS England of the GMS and the ongoing activities from Genomics England have provided What does the current NHS Genomic Medicine Service involve? impetus to this agenda. However, recent evidence suggests that delivering integrated • A national genomic laboratory network made up of seven Genomic and significant service change on the scale Laboratory Hubs (GLHs), which have evolved from the original set out by the Government is not always 13 Genomic Medicine Centres straightforward.22 • A national Genomic Test Directory (Test Directory) to underpin the Our research found recognition genomic laboratory network covering rare and inherited disorders from the expert community about and cancer and from single genes to whole genome sequencing; the challenges facing the GMS which is • A national whole genome sequencing provision and the data still in its infancy. A set of areas emerged and informatics infrastructure, including a Clinical Interpretation as requiring significant investment in Pipeline secured through a partnership with Genomics England; order to mainstream services in the NHS in England. • Integrated clinical service (built by restructuring the existing clinical genetics service) and an evolved role of the NHS Genomic Medicine “There are severe shortages Centre infrastructure; and for certain specialities. • A national coordinating and oversight function within NHS England Bioinformaticians are so (the Genomics Unit) in demand now within the NHS, you really struggle to find them.” 13

14 Coming of Age? Translating Generation Genome into mainstream clinical practice

15 Chapter Two

Figure 4: The national infrastructure for genomic medicine. Source: NHS England, 2019

Political oversight: DHSC & Ministerial Board NHS Genomic Medicine Service

Genomic Medicine Centres National Network of National Test Directory & Genomic Clinical Services Genomic Laboratories Strategic Oversight

Informatics systems National Whole Genome Genomic Data & data store Sequencing Provision Interpretation

Industry/academic/ with HEE GEP Workforce development international partnerships

Built on existing provision developing capacity to deliver future technologies + Strong ethical framework & effective consent + Reflecting diversity of the population

System design must embrace services, but that this is ongoing rather During our roundtable meeting, it was expertise, but also avoid unequal than complete. This has been recognised therefore agreed that equity (rather than access to genomic profiling. by the previous CMO. Giving evidence to equality) of access should be a defining the same Science and Technology Select principle, but that should not mean that When giving evidence to the House Committee in June 2019, Professor Dame the same service would be provided in all of Commons Science and Technology Sally Davies admitted that “achieving centres. Centres with specific specialisms, Select Committee in early 2018, the then change in the NHS is never fast”.23 for example with heritage in target hotspot Chief Medical Officer (CMO) Professor testing or broad panel, should be allowed Dame Sally Davies said that NHS England Interviewees also highlighted that each of to continue and extend their expertise. would seek to ‘mainstream’ the GMS in the 13 Genomic Medicine Centre (GMC) There was agreement that a set of principles the second quarter of 2019.23 Our research areas possessed different expertise and (to be developed by the National Genomics found that whilst NHS England has were at different levels of maturity [a map Board) would be a sensible step to give sought to set out the different elements showing the different areas is shown in sufficient guidance and structure to the of the new structure [see fig 4], it is fig 5]. As a result, there were conflicting 13 GMCs and seven GLHs. evident that more needs to be done to views on whether the GMS should be communicate this with clarity. directive, with control over service design resting with NHS England, or whether the There is limited evidence to suggest that 13 GMCs should be given the autonomy the official ‘launch’ of the GMS in October to choose the services more suitable for 2018 has resulted in a step change for their patient population. Similarly, there patients. Some interviewees admitted was a lack of clarity on whether the GLH that the new Genomic Laboratory Hubs model would eventually subsume, or exist (GLHs), which were allocated under tender alongside the current GMC structure. and are intended to exist alongside the 13 Several participants concluded that the Genomic Medicine Centres, are currently form should follow function: with areas transitioning to full implementation of empowered to make choices in the best interests of patients.

16 Coming of Age? Translating Generation Genome into mainstream clinical practice

“When it comes to the Figure 5: The 13 Genomic Medicine Centres in England. Source: NHS England Genomic Laboratory Hubs, you can’t have all of these labs doing different things, even if people are doing different tests. If you do a test in centre X, you should still receive similar tests in centre

Y. If you can offer a more Lead organisation consistent testing landscape, then you can see how the North East and North UK would become a more Cumbria NHS GMC attractive proposition.” 13 Greater Manchester NHS GMC Yorkshire and Alongside this, it has been acknowledged Humber NHS GMC that the NHS currently needs to rapidly improve its digital infrastructure in order to support implementation of the GMS.11 East of England This has been recognised by various North West Coast NHS GMC other bodies and organisations – who NHS GMC have highlighted key communication and engagement gaps.39 During our roundtable meeting, several attendees commented that West Midlands centres must be allowed to progress with NHS GMC their own “agile” solutions regarding data infrastructure rather than waiting for help from central Government. Oxford NHS GMC

From a national perspective, the role of West of England the National Genomic Informatics Service NHS GMC (NGIS) was identified as being of critical importance – given that it is designed to act as the interface with the network of North Thames Genomic Laboratory Hubs – to ensure NHS GMC clear common standards and protocols. Wessex NHS GMC The recent formation of NHSX is a South positive signal which suggests the South West NHS GMC West London NHS GMC Government is focussed on accelerating NHS GMC digital transformation at scale.24

17 Chapter Two

Alongside this, there is a growing need Figure 6: The Genomics Test Directory. Upskilling the workforce and to establish and embed a clear framework Source: NHS England growing particular specialisms are for patient consent in genomic data. “no-brainer” policies that need to The activities of ‘The Patient Consent What is the Genomic Test Directory? be pursued with real impetus. in Mainstreaming Genomic Medicine Working Group’, convened by NHS • Covers the full spectrum of Simply put, the ability to develop genomic England and Genomics England, has been genomics, from single gene to gene medicine in the NHS will depend on the a welcome move. An initial framework was panels to whole genome sequencing ability and expertise of the people working presented in February 2019, with feedback in the NHS to deliver it.39 Whilst the pace of • invited by Health Education England until Became operational in October 2018 change will differ, our research found that every specialist, including general practice, last April, prior to the final framework • Initial directory was developed with 25 will need to gain an understanding of being published in the coming months. input from two expert groups It is hoped that the final framework will be genomics and its application to their role.34 adopted and be used widely by healthcare • Sets out the different tests available The recent Topol Review underlined the professionals in genomics as a guide for in the NHS for rare and inherited urgent necessity of expanding genomic best practice. The challenges around disorders, and cancer literacy in the NHS.42 Reading and the securing agreement from patients and • Covers England only interpretation of the genome was listed wider public reassurance about genomic fourth out of the top ten digital healthcare medicine are explored in Chapter Three. • Currently updated on an annual basis technologies identified by the Review team, Reimbursement flows need • Future technology to be appraised ranked in order of their projected impact to be transparent, coordinated, with support from Clinical and on the NHS workforce from 2020 to 2040 and consistent with clear Scientific Expert Panel (see fig 7). Pools of expertise are relatively consent frameworks. concentrated and shallow – and this was a unanimous conclusion from those who There is also a need to ensure the design As alluded to in Chapter One, there is participated in our research. Certain of the new GMS will ensure transparent no central funding support for any panel specialists – specifically bioinformaticians and consistent access across different tests – meaning that individual areas are – were highlighted as being in exceptionally areas and groups. The current guidance required to identify resource for this activity, high demand. Once analysis of the genome for the use of testing within the GMS drawing on the 2019/20 National Tariff has been undertaken, it will be critical structure is provided by the Genomic Payment System to help inform spending to recruit and train sufficient genomic Test Directory – which specifies which decisions.28 Our research finds this is a counsellors (experts in managing the genomic tests are commissioned by the major barrier preventing the widespread communication of genomic results).10 NHS in England.26 The Directory is a adoption of genomic profiling services welcome move towards ensuring equity in England. Several participants in our The challenge therefore is twofold: rapidly of access to genomic testing. It is however research highlighted the problems that increase the number of genomic specialists, a new resource – and some have already have arisen from the lack of central NHS whilst simultaneously putting in processes highlighted how its design could be England funding for molecular testing and training that all those working in the improved [more information about the beyond WGS, which have been further health service can benefit from. test is included in fig 6]. supported by research from the patient and The absence of clear routes into specialist 29 Concerns have also been raised previously advocacy community. For example, there is careers was identified, whereas one research that inflexibility in the design of the anecdotal evidence that suggested that participant said that the training programme directory could impact on its effectiveness. many organisations are struggling to afford present in many of the Royal Colleges was For example, NHS England has confirmed simple single gene tests such as fluorescence “around ten years behind” where it needed that the directory will only be updated in situ hybridization (FISH) due to to be. Several participants said this could be annually – which means that technological pressures on local funds which can in turn explained by immediate workforce pressures or scientific developments will not be compromise the ability to proceed with a – which have become the most pressing 27 incorporated on a timely basis. Further trial or match patients to the right trial. issue facing the health service with around to this, the process of compiling the Test one in ten posts currently vacant – Directory needs to be more responsive totalling more than 100,000.30 to expert input. An open and interactive Genomic Test Directory, with regular engagement opportunities for external input via the expert groups and clear lines of communications with the GLHs, would better reflect the fast-moving landscape which it is seeking to monitor.

18 Coming of Age? Translating Generation Genome into mainstream clinical practice

Nonetheless, there are signs of progress. Figure 7: Top 10 digital healthcare technologies and their projected impact Health Education England (HEE) has onTechnological the NHS workforce advances to impacting2040. Source: healthca The Topolre and Review, the magnitude 2019 of disruption. commissioned seven UK universities to run a Master’s level qualification in Technology Digital Medicine, Genomics, AI & Robotics Proportion of workforce affected genomic medicine, with a syllabus 2020 2025 2030 2035 2040 designed for NHS professionals that Telemedicine can be explored in a range of depths 1. ranging from a certificate to a full master’s degree.31 Smartphone apps 2. The Interim NHS People Plan provides Sensors and wearables for diagnostics and remote monitoring further clues as to how NHS England 3. and NHS Improvement are beginning Reading the genome 32 to prioritise this area. Genomics is a 4. prominent feature of the report, being Speech recognition and natural mentioned 11 times. Of particular note, 5. language processing NLP it states that there will be a “critical irtual and augmented reality relationship” between the real-world 6. clinical evidence and insights from Automated image aligned industry and research 7. interpretation using AI collaboration for enhanced clinical Interventional and interpretation of genomic information. rehabilitative robotics 8. There was a recognition that investment Predictive analytics using AI in the workforce would require significant 9. resource, but participants also suggested Writing the genome that this could be justified, given that 10. the trajectory for the increased use of genomic medicine in the NHS is very clear. <20% 20% 50% >=80% Arrow heat map represents the perceived magnitude of impact on current models of care and, by inference, on the proportion of workforce affected

What recommendations does this section link to? Recommendation one Recommendation nine A clear genomics workforce plan as Undertake independent assessment of part of the next spending review the value of different tests, based upon clinical effectiveness, data sharing, Recommendation six quality standards and suitability Announce a new £30 million Genomic Cancer Medicine Transformation Fund, Recommendation ten to accelerate the deployment of genomic Introduce reforms to make the testing into mainstream cancer care Genomic Test Directory more responsive and transparent Recommendation seven Introduce clear targets for the number Recommendation eleven of patients to benefit from the new GMS Address disincentives for the most service, with a particular focus on cancer innovative tumour agnostic medicines, by removing additional costs associated Recommendation eight with testing from the assessment criteria NHS England should operate the new Genomic Cancer Medicine Recommendation twelve Transformation Fund, with funds As part of regular agreed reviews, NICE distributed through the current national should undertake a methods assessment structure of Hubs and Centres in 2020 of how new and emerging genomic technologies are assessed

19 Chapter Three Bringing everyone on this journey

20 Coming of Age? Translating Generation Genome into mainstream clinical practice

Chapter Three Securing engagement and trust with patients, the public and the system

Proper engagement on genomics with all elements of the healthcare community, and the public, is vital. We have already seen concern from elements of the medical community regarding genomics policy – specifically in relation to ‘genomic volunteering’.35 It has therefore been welcome to see the UK Government listen to stakeholders and revise its proposals for a genomic volunteer service, which is to be incorporated within the Accelerated Detection of Disease Challenge and will be free to participants.33 Our research has also found that: • There is a need to win over hearts who might immediately come forward “Before genomic testing and minds. Securing engagement and to contribute towards this agenda. trust with patients, the public and the When it comes to data access and was about familial risk, system will not be straightforward industry involvement, transparency but now we’re seeing but is a necessary endeavour. Genomics is paramount.39 One of the easiest exists at the confluence of multiple ways to capture the interest and support the data informing patients’ 13 trade-offs: between public and private, of the public, and wider NHS, will current treatment plans.” between the state and the individual, and be to demonstrate the value that between research that benefits society genomics is delivering right now for compared to immediate clinical utility. the patient and the role it can play It is essential to engage with diverse in accelerating the wider agenda in groups of the public – not just those the NHS around personalised care.

21 Chapter Three

This new reality, whilst exciting, needs Clinical leadership must feel empowered “Every speciality, including to overcome the current clear separation to make decisions on what the priorities in general practice will need between clinical data and research data genomic medicine must be. This is driven by to gain fluency in genomics in terms of their legal and information the need to avoid a situation whereby testing governance frameworks. becomes uncontrolled and the NHS system and what it means to is unable to cope with increased pressure • There are challenges in how to best from those who have undergone tests to them. But what do I see communicate this to the public. expose higher (but still not actionable) risk On one hand, we need to show that in practice? People have factors. The benefits of heightened public genomics is ambitious and potentially awareness of risk factors – and their impact completely unrealistic ground-breaking. But at the same on preventative behaviours – are still being time, we need to avoid exaggerating its expectations about understood, whilst concerns about the 13 capabilities, especially if other elements what it can achieve.” impact of the ‘worried well’ in inundating of the healthcare system cannot adapt the healthcare system has already been • Access must be equitable, even if to take advantage of the potential that raised in Parliament.41 this slows progress temporarily. genomics provides. Proposals to offer WGS to the wider • More information is not necessarily “There’s always this public for a fee were first reported in the the answer. Research has shown that media during our research stage and danger of making genomics the 100,000 Genomes Project appeared to raise widespread concern participants did not always read the an exceptional thing. across the sector.35 There is concern that information given to them – providing genomic volunteering may increase the When in reality it is just more may only confuse further.37 risk of a two-tiered service. As set out by In many instances, it will be about a big technology, and the the Academy of Medical Royal Colleges, presenting information in a way that is access to testing must be aligned with NHS has a long history correct for the intended audience – and the basic principles of the NHS – with of introducing new building up and maintaining public decisions made on clinical need rather 13 trust in official sources of information, technologies.” than ability to pay.39 There is a clear such as the resources developed by moral and ethical obligation for such HEE as part of the Genomics an approach – and the temptation to What recommendations Education Programme.38 water-down such principles in order does this section link to? to mainstream genomic medicine Most importantly, there is a need to Recommendation six must be resisted. balance hope and honesty over what Undertake a widespread genomics genomic medicine can realistically deliver.39 • The public don’t understand how engagement programme across The positive expectations of genomics the research ecosystem feeds clinical the NHS and public, led by Health need to be balanced by the limitations of care. This has been supported by the Education England our current knowledge, and the realities of work undertaken by IPSOS Mori – existing pressures on the healthcare system. which found that the public often Recommendation seven We must also recognise public concern conflate genomics with services like Introduce clear targets for the number around the involvement of industry. blood or organ donation. Instead, the of patients to benefit from the new Recent research discovered that only research called for genomics to be GMS service, with a particular focus 15 percent of the UK public are willing characterised as a form of ‘national on cancer to share their data with pharmaceutical moonshot’ or shared endeavour, linked Recommendation thirteen companies but were more than three times to a wider programme of UK science more likely to share it with the NHS.40 Introduce clear principles for innovation. As highlighted by Lord The only way to tackle this is through an standardised genomic data collection, James O’Shaughnessy during his period linked to the national policy as Minister for Innovation, genomics absolute commitment to transparency – both in explaining how we partner with framework, led by the Office for “breaks down the barrier between Life Sciences and NHSX research and direct care” – because the NHS and in demonstrating how this patient data can be inputted immediately is directly benefitting patients. into research development and deliver a return to the same individual patient which participated in the first place.36

22 Coming of Age? Translating Generation Genome into mainstream clinical practice

Policy Recommendations

As priority actions to be taken forward in the next 18 months, Roche calls for a series of actions to be taken by different stakeholders:

For the Government: 8. NHS England should support, manage and operate the Genomic Cancer Medicine Transformation Fund, ensuring 1. The next Government Spending Review should include a clear that all 13 GMC footprints are able to access proportionate financial commitment towards training the NHS workforce funding, thereby helping to deliver equitable access for the future. Genomic literacy must sit at the heart of future planning, with all healthcare professionals receiving core 9. Genomic tests listed on the Genomic Test Directory and training as outlined in the Topol Review 42 provided through the GMS should receive independent assessment to confirm clinical effectiveness, data sharing 2. The Prime Minister should reaffirm a commitment and quality standards and overall suitability. The assessment to meeting the pledges on genomic medicine set out in the will need to be rolled out nationally to ensure that testing is NHS Long Term Plan and recognise the value of genomics consistent across England. All tests which meet this benchmark to government industrial strategy should be highlighted with recognisable branding (such as is 3. The Budget should announce a new Genomic Cancer seen with the CE marked tests) Medicine Transformation Fund. The Fund will provide 10. Reforms to enable timely updates to the Genomic Test centralised funding for next generation genomic testing, Directory should be announced as part of the new National recognising that the existing tariff system is unlikely to support Genomics Strategy. The Directory should be designed in a rapid rollout of this technology. Funding will be contingent way to allow flexibility as new gene targets are identified from on compelling evidence that each form of genomic test can research and clinical trials, alongside other technological assist with matching NHS patients to a currently reimbursed improvements to genomic testing. There should be clear and cancer medicine in England. Roche calls for the fund to total transparent routes for consulting with expert clinicians £30 million, replicating the same investment made in 2018 in the UK BioBank. To encourage inward investment, the For regulatory and assessment bodies: Government and the Office for Life Sciences should call for 11. As a matter of priority, NICE must update its approach for this figure to be matched with investments from industrial the appraisal of precision medicine molecules – so they do partners in genomic medicine by 2020/21 not factor in the costs of genomic profiling when conducting 4. The National Genomics Strategy must also consider how cost effectiveness analysis. This should be followed by an genomic testing can go hand in hand with reforms to enable expanded role for the MHRA Innovation Office – which faster access to new rare disease and genomically guided should take advantage of Britain’s planned departure from medicines with greater use of conditional funding for these the European Union to adopt innovative approaches to the products to explore the value they bring regulation of new medicines

5. The Strategy should also set out a clear plan for how researchers 12. As part of the regular review of methods and processes and those developing new treatments can use and access announced alongside the Voluntary Scheme for Branded pooled genomic data, with an immediate focus on cancer Medicines Pricing and Access, NICE should undertake a review of how new and emerging genomic technologies are For the NHS: assessed. The review should take place next year, rather 43 6. The benefits of genomics should be communicated to those than post 2020 as currently scheduled working in the NHS, patients and the wider public, with an 13. When the full policy framework for data sharing being emphasis on patient case studies, particularly in areas such as developed by NHSX and the Office for Life Sciences breast cancer where genomic testing has helped match patients (OLS) is published later this year, it must incorporate clear with new treatments.16 This activity should be led by Health rules for standardised genomic data collection. NHSX Education England, continuing activity from its Genomics should be responsible for setting the ‘rules of engagement’, Education Programme but on a larger scale and with increased communicating these across the NHS in England and resource and collaboration with leading third sector partners ensuring adherence – this should in turn feed into any 7. The National Genomic Medicine Service should set clear certification method for appraising different tests targets for the number of patients to benefit from the service, with an intention to demonstrate improved outcomes in clinical priority areas such as cancer

23 Conclusion Coming of age? The next steps for genomic medicine

This report, drawn on a range of expert insights, has set out some of the considerations and questions we must grapple with as genomic services mature in the UK. How will we know when genomics has ‘come of age’? If the recommendations contained within this report are met, then it is likely that by 2021 we may see an established genomic medicine service as part of mainstream NHS clinical care.

This will not be the end of the story. One other well-deserving healthcare priorities.45 of the biggest challenges facing genomics Failure to recognise the impact of molecular is its breadth. It has the potential to touch developments on patient outcomes is so many different aspects of medicine, understandable and common. But it is the which in turn can make it challenging to responsibility of all those with an interest prioritise and direct resources accordingly. in this area to argue with passion and the There is also a need to overcome cynicism necessary enthusiasm for what genomic over whether efforts to embed genomic medicine can – and must – achieve. medicine should be pursued now, ahead of

24 Coming of Age? Translating Generation Genome into mainstream clinical practice

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