30 September 2016 1
Genomics and personalised prevention Dr Tom Fowler, Deputy Chief Scientist & Director of Public Health European Health Forum, Gastein 29 September 2016
About me Tom Deputy Chief Scientist & Director of Public Health, 100,000 Genomes Project 100,000 Genomes Project Sequencing 100,000 genomes from around 70,000 people. Participants are NHS patients with a rare disease, plus their families, and patients with cancer. 1. To bring benefit to NHS patients 2. To create an ethical and transparent programme based on consent 3. To enable new scientific discovery and medical insights 4. To kickstart the development of a UK genomics industry 30 September 2016 3
Definition of public health "the science and art of preventing disease, prolonging life and promoting health through organized efforts and informed choices of society, organizations, public and private, communities and individuals." Winslow, Charles-Edward Amory (1920). 30 September 2016 4
New era what is personalised prevention? Takes into account individual susceptibility to disease risk (biological) Individual values (socially and culturally determined) And need for autonomous decision making about the take-up of preventive interventions. Individual response to interventions Personalised prevention = Personalisation of risk assessment and interventions for the individual at any age. PHG Foundation, 2015 30 September 2016 5
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? 6
The four P s of personalised medicine 1. Prediction and prevention of disease 2. More precise diagnosis 3. Targeted and personalised interventions 4. A more participatory role for patients 30 September 2016 7
Improving outcomes through personalisation Improves outcomes Targeted therapy Identification of effective personalised treatments 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 Targeted disease prevention Identification of predisposition markers or underlying processes can predict future disease Delivering the 4 Ps of Personalised Medicine Prediction (& prevention) of disease, More Precise diagnoses, Personalised and targeted interventions More Participatory role for patients 8
The strategic approach - tailoring treatment & management to a patient s individual makeup Now 2020 One size fits all treatment based on symptoms Organ/ speciality organisation of services and professions Limited use of genomic and molecular markers Diagnostic and other clinical data not linked New taxonomy of medicine based on underlying cause and personal response Comprehensive linked diagnostics to give a full picture of patient Tailored, more-effective therapies for better outcomes Integrated clinical services taking a whole body approach One size fits all treatments & intervention Individuallytailored approach Increasingly precision interventions based upon carefully identified subgroups within the broader population https://www.england.nhs.uk/ourwork/qual-clin-lead/personalisedmedicine/ 9
Shaping healthcare through a wealth of new information Technology, Innovation & Knowledge Base Clinical Change Model DNA Genomics Transcriptomics Informatics and digital health Phenotypic characterisation & diagnostics Patient Self-reporting Proteomics Metabolomics Personalised Therapeutics Policy & System Alignment Infrastructure 30 September 2016 10
Exploring the early areas for delivery of personalised medicine Cancer Rare disease Learning Disabilities Mental Health & dementia Introduction of gene panels and where evidence supports use of WGS Use of molecular markers in specific clinical conditions (e.g. CML) Introduction of WGS and rationalisation of current genetic testing Embedding of lessons learnt from DDD project and use of WGS for specific conditions Use of genomics to identify possible adverse drug reactions WGS and other genetic testing for specific conditions Cardiovascular disease Adverse drug reactions Maternity & children Diabetes Specific genomic markers for Familial hypercholesterolemia WGS for inherited cardiac disease Specific genomic markers focusing initially on Warfarin Systematic introduction of Non Invasive Prenatal genetic testing WGS in undiagnosed and failure to thrive neonates in ITU Systematic use of specific genomic markers of different types of diabetes WGS for inherited metabolic disease 30 September 2016
Genomic diagnosis guides clinical management in neonatal diabetes MODY (maturity-onset diabetes of the young) Another more common, form of monogenic diabetes Patients have higher fasting blood glucose which is regulated around a stable set point and so often misdiagnosed with T1D or type 2 diabetes Often identified during routine antenatal screening and misdiagnosed as gestational diabetes No treatment required - stopping therapy reduces costs and improves quality of care Stratified approach to MODY is highly important with new tools available to support KCNJ11 p.v59m Permanent diabetes and developmental delay EIF2AK3 p.e371* Wolcott Rallison Syndrome FOXP3 c.227delt IPEX syndrome GATA6 c.1448-1455del Syndromic pancreatic agenesis STAT3 p.t716m Multi-organ autoimmune disease implementation e.g. DNA sequencing technology - allow a single test to be used for all known genetic subtypes Exemplar Sulphonylurea clinical pathways Liver for a stratified Bone approach Marrow to diabetes, Insulin and Sep exocrine 2016, Academy? STAT3 of Med Sciences therapy Transplant Transplant supplements inhibitor 30 September 2016 Five babies: five different treatments Knowledge from personalised medicine 12
NHS Genomics Medicines Centres: the infrastructure for the future 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 GEP HEI x10 Integrated with workforce development led by HEE Genomics Programme upskilling workforce with access to newly commissioned MSc in Genomic Medicine 12
The vision: A move from illness to health ILLNESS Delayed diagnosis Late stage disease Multiple conditions Restricted treatment & management options Poorer outcomes & patient experience HEALTH 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 14
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 15
Credits Chief Scientific Office for NHS England, Prof Sue Hill PHG Foundation Academy of Medical Sciences 30 September 2016 16
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