The national context: The NHS Personalised Medicine Strategy Professor Sue Hill OBE @CSOsue Chief Scientific Officer for England 16th June 2016

Requirements for the future NHS - Forward View Improved Prevention Better integration Data to link everything together New models of delivery (& improvement of old) Need to address ‘big three gaps’ Health & wellbeing Finance & Efficiency Care & Quality Places emphasis on disruptive technology & scientific advances – Forward View recognises that its aims won’t come through gradual evolution

Addressing the gaps to deliver the future NHS Care & quality gap Health & wellbeing gap Finance & efficiency gap The NHS as a social movement with a new relationship with patients and communities, and a focus on prevention New models of care Multispeciality providers Primary and Acute care systems 7 day services Testbeds & Vanguards Improving existing models Challenging variation Standardisation& networks Strategic programmes (eg cancer) Enhanced health in care homes Utilising technology & information Data,informatics & connectivity Large scale initiatives (eg genomics) Telehealth, monitoring Accelerated access Sustainable resourcing, prototyping and assessment

Utilising technology and information 100,000 Genomes Project In 2012 PM David Cameron launches 100,000 Genomes Project made possible due to the decreasing cost of sequencing and developments in computational power and data analytics “By unlocking the power of DNA data, the NHS will lead the global race for better tests, better drugs and above all better care. Utilising technology and information 100,000 Genomes Project Major legacies for patients, the NHS and the UK economy by 2017 Increased discovery of pathogenic variants leading to new treatments, devices and diagnostics Key Principles A focus on rare inherited diseases and common cancers Patients to be drawn from routine care and treated through routine channels All participants to provide a fully informed consent providing for a wide range of data and tissue capture and broad categories of use including research and industry However neither data nor tissues to go outside NHS-controlled ‘safe havens’ and all users to be properly authorised and monitored A separate (government owned) company – Genomics England – formed to coordinate the project under an independent board, providing a ‘start-up’ mentality and drive Accelerate uptake with advanced genomic medicine practice integrated into the NHS Increase public understanding & support for genomic medicine Stimulate and advance UK life sciences industry and commercial activity in genomics Whole genome sequencing is providing a step change in the NHS diagnostic repertoire

Scope of the 100,000 Genomes Project 170+ rare diseases currently in scope with more under consideration with a clear process for assessing new conditions. Aims of RD Programme include: To add value with additional biological insights from WGS To develop a programme of functional multiomics pathways & biomarkers To create a unique dataset for rare diseases that may enable therapeutic innovation 7 common cancers currently in main 100,000 Genomes project ( Breast, Colorectal, Lung, Ovarian, Prostate, Renal, Sarcoma,) with 7 more being added Aims of Cancer Programme include To identify novel driver mutations of common cancers Identify value of WGS in predicting response to therapy To identify new pathways for therapies Aligns with the broader strategy for these areas set out in the Cancer Taskforce report and the UK strategy for Rare Diseases 9

NHS Genomics Medicines Centres: the infrastructure for the future GEP HEI x10 Nationwide network of 13 NHS Genomic Medicine Centres (GMCs) for populations of ~3- 5million with multiple local hospital trusts in their area as delivery partners (~80-100 hospitals in total) NHS GMCs provide: Identification of suitable patients from routine care Involvement of patients in ethics, data & consent issues Supply of high-quality processed samples Collection of linked phenotypic and clinical data Validation of WGS findings and feedback to patients Established operating models for the future across key areas of delivery driven by focus on innovation including: Ethics, consent & patient participation Standardisation and streaming models of care Data collation and handling Partnership and network working, inc new Genomic MDTs Clinical Leadership for change Integrated with workforce development led by HEE Genomics Programme upskilling workforce with access to newly commissioned MSc in Genomic Medicine 12

13 NHS Genomic Medicine Centres working in a national network How the elements of the Project fit together Fire wall 13 NHS Genomic Medicine Centres working in a national network Clinical samples and patient data ( diagnostic and clinical) Laboratory processing including molecular pathology Broad consent for research and re-contact Validation and feedback to participants/clinical teams Biorepository Sequencing DNA & samples for multi-omics Clinical Data Identifiable clinical data Longitudinal Linked to genomic data Research Data Deidentified GeCIP and industry partners work within data centre Participants Data Existing Clinical Data Cancer & RD registries, HES, Mortality data, etc Data and Analysis Improvement Annotation & QC Scientists/SMEs Product comparison Oversight: Funding: Other countries of UK and other international collaborators working to specification set down by NHS England Clinicians & Academics Training Industry

Building the future of genomic medicine within the NHS Develop structures for collection in NHS of consistent, high-quality consent, data and samples (for clinical AND research usage) Develop and deliver a legacy of infrastructure: sequencing centre, sample pipeline, biorepository and large-scale data store, for sustainable use by the NHS. Human capacity and capability Concentrating the UK Genomics Knowledge base (clinical and research) in a single location – with informatics to support access & use in frontline services NHS England to embed Whole Genome Sequencing into routine commissioning of clinical pathways with sharing of all genomic molecular data NHS, academics and industry partnerships working together at the outset to drive Genomic Medicine into the NHS

The vision: A move from illness to health Delayed diagnosis Late stage disease Multiple conditions Restricted treatment & management options Poorer outcomes & patient experience Using science and technology to improve outcomes and health through Prognosis Earlier disease stages offering more treatment options Influencing lifestyle factors Stratified medicine This will deliver the 4 Ps of Prediction (& prevention) of disease, more Precise diagnoses, Personalised and targeted interventions with a more Participatory role for patients

Building the personalised medicine strategy The NHS England Personalised Medicine Strategy will build on: the knowledge & transformation of the 100,000 Genomes Project & the expectations for the future the existing specialist laboratory infrastructure and its reprocurement the other cutting-edge diagnostics available the wealth of patient and clinical data produced through the NHS’s unique integrated operation. The strategy will define personalised medicine as: a move away from a ‘one size fits all’ approach to the treatment and care of patients with a particular condition, to one which uses emergent approaches in areas such as diagnostic tests, functional genomic technologies, molecular pathway, data analytics and real time monitoring of conditions to better manage patients’ health and to target therapies to achieve the best outcomes in the management of a patient’s disease or predisposition to disease. Diagnostics cost NHS £10bn per year Drugs cost NHS £13bn per year. Rise of non-communicable disease + recognition in pharma industry that blockbuster ‘one size fits all’ drugs are only effective in 30-60% of patients

Benefits of personalised medicine: Improving efficiency and outcomes £ Improves outcomes Targeted therapy Identification of effective personalised treatments & adverse drug reactions Accelerated diagnosis based on underlying cause and incidental findings – rather than just grouped symptoms Early disease detection 2-8 yrs before onset & symptoms become obvious with low cost stratification and intervention Targeted disease prevention Identification of predisposition markers or underlying processes to predict future disease & enable integrated approach with PH Delivering the 4 Ps of Personalised Medicine Prediction (& prevention) of disease, More Precise diagnoses, Personalised and targeted interventions More Participatory role for patients .

Building from a genomic base to developing personalisation of care Technology, Innovation & Knowledge Base DNA Genomics Metabolomics Personalised Interventions & Therapeutics Clinical Change Model Infrastructure Policy & System Alignment Transcriptomics Proteomics Patient generated data & self-reporting Integrated phenotypic characterisation Functional diagnostics Informatics and digital health

Medicines & other interventions Delivering Personalised Medicine - tailoring treatment & management to a patient’s individual makeup Providing effective coupling of diagnosis and treatment Diagnostics (inc WGS) Data and analytics Medicines & other interventions Existing and repurposed drugs Targeted medicines Non-pharma New discoveries ‘One size fits all’ treatments & intervention Individually-tailored approach Increasingly precision interventions based upon carefully identified subgroups within the broader population

Early opportunities for personalised medicine underpinned by genomics PM Where significant variation in patient response evident eg Diabetes Where familial links poorly identified Where variation in access exists Where new diagnostics can be applied eg Cancer Where adverse drug reactions significant Eg Warfarin therapy Where important to support a population-based approach eg FH Development of personalised medicine is a multi-dimensional activity: Evidence base for utility/cost effectiveness Responsiveness & turnaround time for results Evolution of Informatics and analytical platforms Integrated and coordinated diagnostics Whole pathway approach Rapid near patient testing Robotic molecular platforms Locally-organised care spectrum of locations

Academic partnerships at the forefront of discovery & innovation Invention Evaluation Adoption Diffusion Research councils/ funders NIHR Innovate UK (Technology Strategy Board) NHS Regional Innovation Hubs NHS England Innovation Initiatives AHSNs NHS Supply Chain Local Commissioning (CCGs) NICE (Medical Technologies Advisory Committee & Implementation Collaborative) Rapid Review Panel (DH) Exemplar clinical pathways (AcMedSci) UK Pharmacogenetic & Strat. Medicine Network UK Clinical Research Collaboration (UKCRC) GeCIP – bringing 2400 researchers from 300 institutions in 24 countries in 39 domains across cancer, rare disease and cross-cutting issues 2014 Government agencies and Non departmental public bodies Shaded are support infrastructure ?3 yrs

The ethical frontline of scientific advance Many new technologies are bringing with them ethical challenges - such as the use & handling of data, or if they have predictive ability – but issues can occur if science is felt to move too fast…. or too slowly How far should the science go? Are the public ready?

Steps towards a better future National approach to commissioning of tests and clinical pathways to ensure equity of access Adopting a systematic way of stratifying patients with standardisation of tests & thresholds and use of risk calculators Functional genomic pathway fully deployed (in real time care and also for monitoring) Medicines and other therapeutic interventions optimised Closer alignment between clinical practice & research for mutual benefit and improved outcomes for patients New partnerships with industry Patients empowered to create truly participatory environment Validating & communicating the economic argument Building capability capacity and engagement Shift in mindset associated with a new taxonomy of medicine Recognising iterative & developing nature of this process

Hold & deliver the vision – the time has never been more right The New Frontier is here whether we seek it or not. Beyond that frontier are uncharted areas of science and space… unsolved problems…. unanswered questions… It would be easier to shrink from that new frontier, to look to the safe mediocrity of the past… But I believe that the times require imagination and courage and perseverance John F Kennedy, 1960