1. Matthew Watkins YHGMC Informatics Programme Manager mw@nhs.net 07825 781111 http://lnkd.in/mrQT3j 100,000 Genome Project. Yorkshire and Humber Genomics Medicine Centre. YHGMC Informatics Programme and Local Delivery Partners.

2. What is genomics? Genomics is the study of the whole genome and how it works but has also come to have a broader meaning to include the way that the genome is interpreted and the technologies that have been developed to help do this. A genome is an organism’s complete set of DNA, including all of its genes. Each genome contains all of the information needed to build and maintain that organism. In humans, a copy of the entire genome—more than 3 billion DNA base pairs—is contained in all cells that have a nucleus.

3. 2003 Human Genome Project One of the most significant scientific breakthroughs of modern times - the blueprint for building a person The complete genetic code of a human being is published… two years ahead of schedule

4. Cost and time - 1990 to today To get to 2003 the cost has been estimated at $2.3 billion and took 13 years. Commercial companies are now offering $1,000 sequencing and a turnaround of 26 hours. This will only get cheaper and faster.

5. Total cost of sequencing a human genome as calculated by the National Human Genome Research Institute

6. December 2012 - The 100,000 Genomes Project launched David Cameron launches the project to sequence 100,000 Genomes from NHS patients to cement UK as a world-leader in Genomic Medicine Ambition - transform diagnosis and treatment for patients with cancer and rare diseases Genomics England (owned & funded by the Department of Health) is set up to deliver the project.

7. A co-ordinated response across health and care Co-ordinating genomic knowledge to make the UK a world leader Sequencing 100,000 genomes to advance genomic knowledge Turning genomic knowledge into health interventions Ensuring the NHS Workforce is skilled and able to deliver for patient benefit Using genomic knowledge for prevention and health protection

8. Four aims 1.to create an ethical and transparent programme based on consent; 2.to bring benefit to patients and set up a genomic medicine service for the NHS; 3.to enable new scientific discovery and medical insights; 4.to kick start the development of a UK genomics industry. The focus is on patients and families with a rare disease with cancer

9. LEGACY “…a genomics service ready for adoption by the NHS, high ethical standards and public support for genomics, new medicines, treatments and diagnostics and a country which hosts the world’s leading genomic companies.“ The routine use of DNA sequencing in mainstream healthcare

10. Personalised Medicine Strategy 2015 NHS England Board – September 2015 Author - Sir Bruce Keogh, National Medical Director. A Personalised Medicine service in the NHS embracing four overarching principles i. Prediction and prevention of disease. ii. More precise diagnoses. iii. Targeted and personalised interventions. iv. More participatory role for patients. GMCs are a stepping stone towards Personalised Medicine and will inform the development of the NHS England Personalised Medicine strategy

11. 16 December 2015 - Yorkshire & Humber Genomics Medicine Centre is announced. There are now 13 designated Genomic Medicine Centres across England. “New NHS centres add their might to world-leading genomics project Two new NHS Genomic Medicine Centres have today been unveiled as being part of the unique, innovative and world-leading 100,000 Genomes Project.”

12. Professor Sue Hill, the Chief Scientific Officer for England “another step towards NHS transformation. ” “The more people who come forward to participate in the Project, the greater the body of knowledge there will be to inform diagnoses and patient care in the future.”

13. Nationwide network of 13 NHS Genomic Medicine Centres – each serving 3- 5million population Each NHS GMC lead ‘contractual ‘ organisation works with local hospitals as local delivery partners Integrated with existing regional genetic laboratories and clinical genetic services and local pathology laboratories Mapped to Academic Health Science Networks (Y&H AHSN is based in Wakefield) Universities The infrastructure for delivery GEP HEI x9

14. Consent & Sample collection DNA extraction Bio- repository Sequencing Variant Calling Interpretation Feedback to clinician Validation Treatment Clinical Data The Genomic Treatment Cycle GMCs GeCIPs GeCIP - Genomics England Clinical Interpretation Partnership Sequencing Centre Wellcome Trust’s Sanger Institute near Cambridge.

15. Programme legacy will see: High quality sample preparation and use of high throughput and novel genomic technologies Richer phenotypic data linked to genetic abnormalities and markers Strong informatics infrastructure and interoperability Stronger link between clinical practice and applied genomics New multidisciplinary teams – involving many more clinicians Improved clinical leadership and delivery of the clinical change model Improving outcomes for patients and reducing variation in clinical care Staff education in genomics Standard data Recruitment & Consent Integration of IT systems and data capture Clinical Engagement Sample Acquisition Optimised & Standardised Processing including in molecular pathology National Lab QA process Multi-omic pathways DNA Extraction Unique data sets Enhanced data quality Phenotypic Data Enhanced capacity in bioinformatics & diagnostic testing Enhanced clinical interpretation Validation & Reporting Key future benefits which are directly influenced by the NHS GMC sample and data pathway are shown in the diagram below Future benefits for the NHS Workforce education in genomic medicine Collaborative working/ networking across NHS GMCs and LDPs Continuous improvement of data and sample quality/ sharing best practice

16. 16 Genomic Medicine is important in improving outcomes Targeted disease prevention Identification of predisposition markers or underlying processes can predict future disease Early disease detection 2-8 yrs before onset & symptoms become obvious with low cost stratification Accelerated diagnosis based on underlying cause and incidental findings – rather than just grouped symptoms Targeted therapy Identification of effective personalised treatments Improves outcomes Greater efficiency from streamlined care pathways Earlier and more precise diagnosis and treatment Fewer and less complicated surgical interventions Fewer patients getting cancer and other diseases £

17. March 2015: First adults receive diagnoses Dec 2015: First children receive diagnoses Mobilisation across the NHS GMCs has seen significant rise in recruitment & samples 6,351 genomes sequenced by end of 2015 (8469 May 2016) High quality DNA to maximise WGS integrity - 100% pass rate at Biorepository Detailed data models for rare disease and cancer and development of associated informatics & clinical tests Genomics England working together with NHS GMCs have established world-leading approach to cancer tumour processing Significant buy-in from hospital management and senior leaders NHS Achievements to date

18. Lots of engagement with clinical colleagues, true collaborative working. Rare diseases. Processes mapped and current state understood. Web based systems developed and live. Pathways operational with patients being recruited, data collected, samples taken, tracked and sent to the national bio bank. Cancer. Processes mostly mapped. Cancer systems in development and cancer dry run planned for June 2016 with go live June/July 2016. Local Delivery Partner engagement underway. Mid York’s (April 2016) NYHDIF (today ) Y&H GMC Informatics Achievements to Date

19. Success hinges on collaboration & integration of clinical data Personalised medicine requires information to form an integrated clinical picture which can be used to tailor treatment Informatics and shared reporting will play a major role in increasing the impact of care, bringing all the elements together to maximise knowledge about an individual and give the clearest picture of their condition Coordination of data and information analysis will be central to the work of healthcare in the future

20. Patient Participation and Consent Key points Voluntary Informed consent Consent can be withdrawn Rigorous Information Governance “Participant privacy and confidentiality is vital in the 100,000 Genomes Project. A key feature of the Project is that an individual’s data will not be released. Instead, data is analysed within a secure, monitored environment.” The GMC will be the hub for communication, guidance, advice and reassurance on ethical and consent issues

21. Patient pioneers Mary, Kerry and Sandra - three sisters diagnosed with breast cancer within 13 months of each other - are hoping to find out if other family members could be at risk of breast cancer. "Joining the project might provide the answers to help future generations of my family as well as other people." "This project gives us real hope to try and identify new genes and plan treatments based on genetic alterations we find in the patient's blood or tumour."

22. Patient pioneers Clinicians from Great Ormond Street Hospital (GOSH) are able to give them a molecular diagnosis, setting them free to make decisions about the treatment options for their child and how they move forward with future plans for their family. “Now that we have this diagnosis there are things that we can do differently almost straight away. Her condition is one that has a high chance of improvement on a special diet, which means that her medication dose is likely to decrease and her epilepsy may be more easily controlled. Hopefully she might have better balance so she can be more stable and walk more. She’s now four years old still looks like a wobbly toddler trying to move around!”

23. The next 4 years ‘One size fits all’ treatments & intervention ‘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 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 Now 2020 Individually - tailored approach Increasingly precision interventions based upon carefully identified subgroups within the broader population

24. Key factors in delivering the future Effective adoption and delivery of new technologies for patient benefit is both a hearts and minds exercise – it requires a rethinking of ways of working and can’t just be layered on top of existing practice Ensuring the technology is enabled Ensuring existing working practices have been rethought and respecified

25. Y&H GMC Informatics Programme Working with the Local Delivery Partners

26. Working with Local Delivery Partners in the Region The lead organisation is Sheffield Teaching Hospital Leeds Teaching Hospital (which is hosting the informatics component of the YHGMC) and Sheffield Children's Hospital have gone live for rare diseases and will go live for Cancer soon (June/July 2016). LDP’s have an integral role in the success the GMC services in the region Looking for early engagement with local delivery partners now. This will be clinically lead but informatics early engagement is also key to success.

27. * Provide a link between people in the region with the same condition * Encourage local participation - ‘genomics where you live, genomics in your hospital’. * Local identity for a national initiative, harmonising the national and the local. A genomics programme with strong regional links

28. Greater efficiency from streamlined care pathways with genomics embedded as standard. Improved laboratory services Earlier and more precise diagnosis and treatment Fewer patients with cancer and other diseases Higher recovery rates. The right patient gets the right treatment at the right time - regionally improved outcomes Make genomics a reality for the region with high quality, effective and affordable systems

29. A driver of good practice and collaboration Provide regional governance and regional focus Accelerate and increase the power of local networks, technologies and services (e.g. existing Genetics Services in Sheffield and in Leeds). Ensure equality of services across the region (common records, digital, accessible information) Promote standards and support their acceptance and take up (ITIL, GS1, ITK, IG toolkit etc.) Collaborate with, link and assist Local Delivery Partners Good practice finder and collaborator with other GMC’s

30. In 2015 Chief Executives across the region signed statements of intent. Re: Yorkshire and Humber Genomic Medicine Centre – Local Delivery Partner expression of support. We are pleased on behalf of The NNNNNN NHS Foundation Trust to confirm our intention to be an integral part of the Yorkshire and Humber Genomic Medicine Centre (“GMC”) by becoming a local delivery partner in the delivery of the GMC services (“LDP”). We have been engaged in the development of the bid for the Yorkshire & Humber GMC and I know that our clinical teams have been made aware of the purpose and operational processes that will be required from us as an LDP to support our GMC. We are aware that the implementation of the GMC across the region will be progressive and that there will be resources made available to LDPs to ensure our ability to comply with the national and local requirements of appropriate consenting of patients and the management of samples acquired. We understand that the three core partners: Sheffield Teaching Hospitals NHS Foundation Trust, Leeds Teaching Hospitals NHS Trust and Sheffield Children’s NHS Foundation Trust (the “Core Partners”) have developed a partnership agreement setting out the manner in which they will work together to deliver the bid for the GMC services and for the delivery of those services should the bid be successful (the “Partnership Agreement”). We understand that in the event the Core Partners submit a successful bid, Sheffield Teaching Hospitals NHS Foundation Trust will enter into a contract with NHS England for the provision of the GMC services on behalf of the Core Partners. Whilst our organisation will not be a party to that contract, we understand that the level of our input, including volumes, operating procedures and timescales, as well as the resources to be made available to us, will be set out in appropriate commercial arrangements between ourselves and the Core Partners. As an LDP, we will have an integral role in assisting the Core Partners in their delivery of the GMC services in our region. We agree that maintaining a collaborative approach to the bid and to the provision of the GMC services will be essential to the success of the GMC. We look forward to the rapid implementation of the GMC and for the potential transformational benefits across our region to be realised.

32. What’s the impact on clinical services? This detail hasn’t emerged yet. Will be lead by clinical colleagues. Early engagement is the key. Clear understanding needed. Readiness for the short term and preparation for the transformation

33. YHGMC – By December 2017 Cancer – 4700 Rare Diseases – 2599 Cancer – 316 per month Rare Diseases – 130 per month

34. Task Name Doncaster and Bassetlaw (RD4%/C4%) Hull and East Yorkshire (RD3%/C13%) Mid York's (RD1%/C9%) Bradford HFT (RD7%/C8%) Task Name Barnsley (RD2%/C0%) Rotherham (RD2%/C1%) Calderdale and Huddersfield (RD1%/C6%) Harrogate (RD0%/C3%) North Lincs and Goole (RD2%/C8%) Airedale FT (RD1%/C4%) York (RD1%/C6%) LDP Targets

35. What's available now. Process mapping done and shareable. Web based systems developed for rare disease essential data set. Web based systems in development for cancer essential data set and available June/July 2016. Training and support available for colleagues. GMC informatics team available to work with local partners on aligning and improving processes, providing systems, advising on system development and supporting integration. Next few months – tactical Moving to support transformational change

36. Next steps. Identify/volunteer informatics lead in each LDP Link them to emerging LDP clinical leads Share knowledge, process maps and data sets Explore integration with LDP systems if this is the LDP strategy Provide access to the existing systems for patient consent, sample tracking and case note capture as a short term measure if local solutions will eventually perform these functions Provide access to the existing systems for patient consent, sample tracking and case note capture as an on-going solution if that aligns with LDP strategy Create conditions where the technology enables mainstreaming of genomic medicine Project management Service management

37. Thank You