MRC Stratified Medicine Initiative Jonathan Pearce Medical Research Council, Translational Programme Manager Pharmacogenetics and Stratified Medicine Network Conference : 14 th January 2015
Stratified medicine has the potential to deliver improved diagnoses and therapies Input Tools Outputs Value Affected Disease Strata population - Mechanism of disease leading to Clinical new therapies Presentation /Phenotype - Diagnostics to better predict disease state, prognosis, Genetic / Therapeutic response Molecular Response 1
It is moving beyond its historic bases in oncology/infection and genomics/IHC • Current - infectious diseases and oncology • Future - anticoagulants, antipsychotics, Disease area autoimmune diseases, asthma, COPD, diabetes, and pain • Current – genomic and immunohistochemistry Technology • Future – mRNA, proteome, epigenome, metabolome, etc 2
MRC Stratified Medicine Initiative • Set up in 2010/11 and represented a new way of funding from the MRC • Builds on the MRC/ABPI Inflammation and Immunology (I&I) Initiative • £60m initiative to develop disease-specific research consortia, involving industry partners • Consortia exploring predictors of response and mechanisms underpinning disease stratification, where there is evidence that therapeutically relevant strata exist • Currently supporting nine consortia (three I&I and six new), bringing together 30 academic and 41 industrial partners 3
Thoughts on what it takes to build a stratified medicine discovery engine • Partnership and team work – no one group has all the necessary skills • New ways of working able to respond to internal and external advances • Access to patients and patient involvement • Platforms to enable biomarker discovery • Biobanks and Technology • Bio and health informatics system able to integrate multilevel data (omic thru clinical records) • Modelling capacity able to both identify statistically significant biomarkers and develop systems biomedicine models of disease mechanism 4
Molecular pathology review • If the UK is to capture the stratified medicine opportunity, we need to be able to translate both its therapeutic and diagnostic outputs to patient and economic benefit • While much consideration has been given to the challenges faced by those developing new therapies, less work has focused on the needs of diagnostics • MRC has undertaken a review focused on these needs 5
Compared with therapies, the diagnostics path is complex & poorly linked Regulatory Modality Developer Type Evaluation Adoption Approval Yes NICE efficacy Drug All All Mandated (TAP) required Yes NICE Not but efficacy Commercial All (DAP) Mandated not required Not Rare Genetic No UKGTN Mandated Diagnostic Hospital Non-Rare/ No - - Non-Genetic The field would benefit from these gaps being addressed and from clear guidance on the path and required evidence for the discovery, development, regulatory approval and evaluation of molecular pathology tests 6
… and the diagnostic development landscape is fragmented Research and Service base has become separated, to the detriment of both Clinical Pathology Research Service Industry UK IVD companies are not well placed to help bridge the divide There is a critical need to bring these various parties into closer proximity 7
Signatures are the future of diagnostic tests and will require close collaboration Biomarker(s) Time Test Assessed Level of single biomarker, HER2, to Current HercepTest predict response to Herceptin Level of expression of 21 genes, to predict Emerging Oncotype DX response to adjuvant chemotherapy Algorithmic signatures of multiple biomarkers from Future different classes (protein, metabolite, etc) to identify disease strata Managing the development challenges of future tests will require close collaboration between researchers, service providers and industry with access to multi platform, data integration and data analysis capabilities 8
Review recommendations • Path - Produce clear unified guidance setting out the critical path and required evidence for the discovery, development, approval and evaluation of tests. Address the gaps in the UK’s regulatory, evaluation, adoption and delivery system • Proximity - Establish joint research/clinical service ‘nodes’ aligned with industry and complementing NIHR, TSB and other RC and partner investments • People - • Train next generation of research leaders in molecular pathology, potential merit of guaranteed follow through clinical lectureships • Further development of UK capacity in statistics, bioinformatics and health economics • Undergraduate medical curriculum to include molecular pathology, to aid adoption and interpretation 9
MRC and EPSRC molecular pathology nodes call • In an initial response to recommendations, the MRC and EPSRC have launched a joint call to support up to eight molecular pathology nodes • Up to £17.5m (£15m from MRC and £2.5m from EPSRC) • Each node will be a multidisciplinary centre of innovative molecular diagnostic test discovery and development bringing together the research base, pathology/genetic services and industry • Research base to include biomedical, clinical, engineering and physical sciences 10
Initial focus on discovery and validation of novel molecular pathology approaches Regulatory Early Late Discovery Evaluation Adoption Development Development Approval • We anticipate nodes will initially be positioned at discovery/early development boundary working on: • Discovery and validation of biomarkers associated with disease strata • Development of novel sensing and analytical technologies for new diagnostic tools • Application of mathematical and statistical methodologies for the extraction of information from complex datasets. • Longer term, we expect nodes to traverse the path to adoption/delivery, as tests under development mature 11
Nodes as virtuous circles - Population use stimulating and supporting research • Closing the circle by complementing and extending current service could stimulate new research by providing real world population level data combining health records with molecular pathology fingerprints • Skimming of existing tissue flows could support discovery and validation • Use of Diagnostic and Research data bins 12
Network and Complementation • Together the nodes will be expected to • cooperate as a network for UK benefit by, for example, sharing best practice and assisting in evaluating and diffusing next gen tests • complement partner investments Discovery Science Early TRL Late TRL MRC Stratified Medicine NIHR Consortia DECs Science Nodes Catapult NHS base EPSRC Analytical Sciences RC Centres MHRA NICE NIHR BRCs/BRUs NHS Innovation 13 Validation Regulation Evaluation Adoption Discovery 13
Conclusion • Working in partnership, the MRC has established a portfolio of stratified medicine consortia that are attracting significant UK and overseas industrial interest and commitment • The joint MRC EPSRC molecular pathology nodes call and complementary partner initiatives, if consistently and clearly presented and built upon, could make the UK an optimal environment for the discovery, development and adoption of innovative molecular pathology tests, to capture the health and economic benefits of stratification 14
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