Orchestrating a National Translational Research Strategy

1. Orchestrating a National Translational Research Strategy John Bell

2. O.S.C.H.R. UK Health Research Analysis • Published May 2006 • First ever comprehensive national analysis of health research funding • 11 largest Government and charity funders of health related research in the UK • Collected peer-reviewed research funded 2004/2005 – £950m/9500 awards • All types of research activity and all areas of health and disease

3. O.S.C.H.R. UK Health Research Analysis

4. O.S.C.H.R. UK Health Research Analysis

6. O.S.C.H.R. Drivers for Change

7. O.S.C.H.R. O.S.C.H.R. Key Findings UK Health research system has many strengths But: • Risk of failing to meet full economic, health and social benefits of UK public investment; • No overarching health research strategy; • Key gaps in the translation of health research; • Funding of health research from concept to practice could be more coherent; • Cultural, institutional and financial barriers to translating research.

8. O.S.C.H.R. O.S.C.H.R. A Single Health Research Strategy • A new, sustainable, strategic framework for health research and cultural change • Continued investment in basic biomedical science • A ‘Health Research Ring-fence’ • Commitment and engagement across all four UK Administrations • New investment targeted in key strategic areas

9. Government Investment in Health Research Millions GBP

10. OSCHR Partners developing a single UK Health Research Vision UK Health Research Vision

11. OSCHR Public Health Board Translational Medicine Board E-Health Records Research Board Human Capital Infrastructure

12. O.S.C.H.R. UK Health Research Priorities Survey of unmet medical need Evaluation of Scientific Opportunity Health economic impact

14. England – Forecast Increase in Diabetes Prevalence by Local Authority District, 2001-2020 The Burden of Disease and Illness in the UK: S. Green, R Miles. April 2007 Source: Yorkshire & Humber Public Health Observatory 2007

15. The Burden of Disease and Illness in the UK: S. Green, R Miles. April 2007

16. England and Wales – Age-standardised rates for three major causes of death (per million population), 1971-2005 The Burden of Disease and Illness in the UK: S. Green, R Miles. April 2007 Source: Office for National Statistics 2007

17. England and Wales – Cancer Mortality Trends – Age-standardised Mortality rates per Million Population, 1991-2005 The Burden of Disease and Illness in the UK: S. Green, R Miles. April 2007 Source: Office for National Statistics 2007

18. Health Research Opportunities 2 Stratification of phenotype Regeneration and replacement Tracking response to intervention Measure, understand and modify environmental and inherited influences on health Exploitation of world leading position in hypothesis-generating science to deliver improved health Early detection of the opportunity for effective intervention Primary prevention Behaviour modification Understanding the burden of illness Development of new interventions

19. O.S.C.H.R. National Institutes for Medical Research, Mill Hill Rebuilding Basic Science Infrastructure MRC Laboratory for Molecular Biology, Cambridge

20. Translational Pipeline

22. O.S.C.H.R. Translational Medicine • Experimental Medicine and Exploratory Development, including imaging, biomarkers: MRC • Methodology for large and small clinical trials: MRC • Large trials and evaluations of therapeutics, devices, diagnostics, and other interventions (overlapping with public health): NIHR • Clinical training: NIHR

23. The complex environment of translational medicine Molecular pathology High throughput screening NIHR, WORD, Scotland DA HTA BRUs BRCs Stem cells Chemistry Cohorts Biobank RNAi Biomarkers Regulation Biologics MRC CRFs Imaging Training Large trials GMP facilities Stratification Cyclotrons AHSCs Genetics Trial Methodology Preclinical models Technology transfer Enabling technology Charities

24. Translational Medicine: Enabling Technology • Imaging • Biomarkers • Drug Safety • Experimental Medicine • Genotype:Phenotype

25. O.S.C.H.R. Large Scale Evaluation Discovery Target identification Phase II and III Trials Developmental Pathway funding Scheme (MRC) Phase I HTS L.I.  L.O. Pre- clinical models Biologics P.o.C. Regulatory Support Safety and Toxicology Manufacturing and Formulation

26. O.S.C.H.R. Biomedical Research Centres (NIHR) • 5 Centres selected in competition • £100 million p.a. support for infrastructure and personnel • Increase capacity in experimental medicine and exploratory development

27. O.S.C.H.R. Well-characterised Small Cohorts (MRC & NIHR) • Common disease cohorts (e.g. COPD, osteoarthritis, heart failure, stroke, hepatitis C, HIV, Alzheimer’s disease) • Phenotyping using imaging, physiology, genetics and genomics • Disease progression monitoring • Maintained for experimental medicine and exploratory development

28. Molecular Diagnostics: The new genetics in clinical practice

29. Translational GeneticsBridging the Gap Translational Funding Research Labs Diagnostic Labs Proof of Concept Clinical Practice Clinical Trials Basic Science

30. Next Generation Sequencing Oxford Nanopore 454 Life Sciences SOLEXA / ILLUMINA

31. Sequencing Projects PROJECTS • Sudden Cardiac Death • Retinal Degeneration • Mental Retardation • Pathogens • HNPCC cancer • CHD • Type 2 diabetes • Renal cancer • Melanoma POTENTIAL TLN OUTCOMES • Improved test for 5-10 genes • New UK /European test • New UK /European test • Infection surveillance in hospitals • Improved test & novel application • New UK /European test • Identification common variants • Pharmacogenetics tests • Signal transduction pathways, Stratified medicine

32. Sudden Cardiac Death Syndromes • Hypertrophic and dilated cardiomyopathies, long QT syndrome • Heterogeneous single gene conditions - autosomal dominant • Incidence 1:500-1:1000 • Condition treatable once diagnosed – lifestyle, beta blockers, defribillators • Oxford GKP programme • Up to 5 genes currently tested for HCM, DCM or LQT • Potential to increase referrals (cardiologists, coroners) & expand genes tested (10) • Technology upgrades required to support this • Once validated can be applied to other established NHS genetic tests (eg BRCA1/2)

33. Retinal Degeneration • Inherited eye conditions • Defects in photoreceptors and retina leading to progressive visual loss • Genes known, but currently lack of comprehensive testing • 25-30 genes known for autosomal recessive retinitis pigmentosa • 200-300 genes for ARRP, ADRP, XLRP and other relevant eye disorders

34. Pathogen Surveillance Clinical applications: Novo virus, MRSA, C difficile, TB • At national level: identify new epidemic strains • At local level: identify endemic outbreaks • Individually: identify pathogen to inform clinical intervention

35. Array CGH-NHS Potential • Develop as first line test for chromosomal anomalies • Multi-sample formats and high density • Cost implications and commissioning (>50% cost efficiency) • Extend Applications • Speech and language / autism • Congenital heart disease • Leukaemia • Pre-implantation genetic diagnosis • Cancer • Diagnosis, prognosis, treatment selection

36. Xp22.11 Father Male proband Male sib (affected) SLI037: ~456kb 3p26.3 loss, ~607kb Xp22.11 gain 3p26.3 Male Proband Father Male sib (affected)

37. Large Scale Evaluation • Therapeutics • Diagnostics • Devices • Other interventions

38. O.S.C.H.R. E-Health • Contribute to developing Connecting for Health for research purposes (Research Capability Program) • Pilot studies with databases in UK (GPRD), Scotland and Wales • Federate databases across UK

40. Benefits - Research • Epidemiology scale follow up of patient cohorts. • Content rich databases allowing integration of data • Evaluation of efficacy and toxicity of therapeutics in real populations • Rapid ascertainment for clinical trials • Novel cohort methodology for evaluations of all forms of interventions

41. Integration of patient data Laboratory data Genomic data E-Health Record Imaging GP record Hospital admission

43. E-Health • Effective systems of record linkage in Scotland, Wales and parts of England (North west and Birmingham) but international competition is growing • Research capability program is delivering tools for research purposes that will work in most systems • CfH is unlikely to be the platform in its current form but multiple exisiting record systems will work together • Governance of data could be limiting factor • We have lost the international lead

44. Why have we lacked in Public Health Research? • Multiple disciplines (epidemiology, infectious disease, modelling, behavioural psychology) • Much is outside the health system and Department (education, transport, workplace environment) • Multiple disease areas (cardiovascular, cancer, infectious disease, mental health, diabetes) • Inconsistent and sparse funding • No career track for professionals

45. Public Health Infectious DISEASE Infectious Disease Infectious Disease Chronic Disease Discovery Discovery Surveillance Evaluation Evaluation

47. Going Global with Public Health

48. Can we do better in Public Health? • Multi-agency/multi-departmental funding • Leadership in a few major areas (addictions and mental health, infections, obesity, ageing) • Obtain national experiments from others (transport, education) • Work with industry

49. The Economy….

50. Maintaining a Competitive Commercial Health Sciences Sector • Pharma pipelines are poor and late stage failures are frequent • Efficacy is low in unstratified populations • Marketing exceeds innovation • Clinical Trials are too slow and expensive • Biotech business model is broken. Gestation is too long and Venture Capital is scarce • Not enough partnerships