Area of investment and support

Area of investment and support: Precision medicine

The aim of this programme is to support and fund research that will identify patients or subgroups of patients with distinct mechanisms of disease or particular responses to treatments, helping ensure that the right patient gets the right treatment at the right time.

Partners involved:
Medical Research Council (MRC)

The scope and what we're doing

MRC’s precision medicine initiative began in 2010 and continues to be a major part of our research strategy, with a commitment of £75 million to fund a range of research consortia.

The overall aim of the initiative is to improve our understanding of how to tailor treatments and interventions to the individual needs of people living with a wide range of diseases and conditions. MRC is coordinating its activities in this area with other charities and funding bodies including Innovate UK, the National Institute of Health Research, the UK Health Departments, the British Heart Foundation, Cancer Research UK and Arthritis Research UK.

MRC and the Association of the British Pharmaceutical Industry (ABPI) inflammation and immunity initiative pilot programmes were launched in 2011 and, following on from this, MRC adopted a disease-focused approach to its precision medicine initiative.

The initiative’s first funding opportunity was in 2012. The consortia that were funded via this opportunity aim to identify and analyse patients to better direct therapy and to gain a deeper understanding of the differing mechanisms of disease and treatment responses. The success of these consortia is based on a multidisciplinary approach, drawing on the expertise of scientists, industry and patient charities, underpinned by the infrastructure of the NHS and the commitment of patients.

In July 2013, MRC held a stratified medicine strategy workshop, to consider how the field’s opportunities and needs had developed. The goal of the workshop was to assess whether, and how, MRC’s precision medicine strategy might need to be changed in order to keep the UK at the forefront of this rapidly developing field. The MRC stratified medicine workshop report contains the workshop background, recommendations and a synopsis of presentations.

In the initiative’s second funding opportunity, held in 2014, we built on lessons learnt from the success of the pilot programmes and the first opportunity. We sought to develop additional UK-wide consortia, each focused on a specific disease area, in order to develop a deeper understanding of the mechanisms underpinning stratification.

The third funding opportunity was held in 2017, where the remit of the call was broadened beyond stratification by response to treatment to include stratification by risk, diagnosis and prognosis. MRC, with co-funding from Cancer Research UK and Arthritis Research UK, supported a further four consortia which had shown a strong case for scientific advancement and major clinical unmet need – paediatric arthritis, prostate cancer, alcoholic hepatitis, and renal disease.

Molecular pathology

Molecular pathology is a discipline that seeks to describe and understand the origins and mechanisms of disease at the level of macromolecules (for example, DNA, RNA and protein) largely using patient samples.

Individual diseases are defined based on a common set of signs and symptoms as well as diagnostic tests. However, these shared signs and symptoms can arise from a variety of disruptions to underlying mechanisms.

For example, patients with type 1 and type 2 diabetes both present with high blood sugar levels over a prolonged period. However, this common presentation has different causes. Type 1 diabetes results from the body’s failure to produce enough insulin and type 2 diabetes from cells failing to respond properly to insulin. This means that not everyone who is classified with the same disease will necessarily experience the same rate of disease progression or respond equally well to the same drugs.

By classifying and understanding the molecular differences between the different groups or strata of people with a shared condition we hope to more accurately diagnose them, better understand how their conditions will progress, and determine which treatments are most likely to be effective. The improved stratification of patients therefore has the potential to deliver significant health and economic benefits.

The UK’s response

In recognition of the potential benefits offered by stratification, UK government and charity funders including MRC, Innovate UK, the National Institute for Health Research, Cancer Research UK and Arthritis Research UK have collectively invested around £200 million in the area, coordinated via the Stratified Medicine Innovation Platform (SMIP).

If the UK is to benefit from this substantial investment and capture the full potential of stratified medicine, it is critical to ensure that there are robust pathways and capabilities to develop and adopt the new diagnostic tests and therapeutic strategies that it will give rise to, as identified in the Academy of Medical Sciences (AMS) 2013 report, Realising the potential of stratified medicine.

Precision medicine consortia

MRC supports a portfolio of 17 consortia, with an investment of around £75 million. Each consortium is a scientific discovery engine with a finely characterised patient population at its heart contributing to a deeper understanding of disease process as well as trialling new and existing treatments in stratified groups for real patient benefit.

The consortia are focused on discovery and understanding of clinically important disease strata, with stratification via response to treatment, diagnosis, prognosis or risk. This is achieved through collaboration between industry, academic, clinical and patient groups. Five consortia are co-funded with charity partners:

  • Cancer Research UK (S-CORT, Re-IMAGINE)
  • Arthritis Research UK (MATURA, CLUSTER)
  • British Heart Foundation (AIM-HY).

Stratified medicine

MRC’s framework for the development, design and analysis of stratified medicine research provides guidance for researchers to consider the fundamental principles of stratified medicine methodology.

The aims of the framework are to:

  • present a pathway for stratified medicine research that starts with the end in mind and covers stratum discovery and verification, leading towards early clinical assessment
  • identify critical questions when designing studies, and draw attention to potential design pitfalls and sources of bias
  • describe methodological approaches and resources to inform study design and analysis, drawing on appropriate guidance and case studies
  • enable investigators working at different phases of the stratified medicine pipeline to integrate their work.

The framework covers six themes:

  1. framing the question and defining the population
  2. designing stratum discovery studies; selecting variables, defining response and powering
  3. assay design; managing complexity and variability
  4. defining strata; data integration, linkage to existing knowledge, linkage to outcome
  5. stratum verification
  6. progression toward clinical utility.

MRC molecular pathology review

In 2013, MRC led a molecular pathology review focusing specifically on defining the need for diagnostics and how they might be addressed, to better enable the potential benefits offered by stratification and molecular pathology to be captured.

The review found there are challenges to the delivery of improved diagnostics from molecular approaches across three domains.

Lack of a defined development path

Compared to therapeutics, the diagnostics development path is complex and poorly linked.

Fragmented landscape

There is separation between the academic, pathology and industry sectors of the diagnostic development landscape.

Complexity of multi-platform signatures

A growing proportion of diagnostic tests will be based upon the assessment of numerous markers drawn from many molecular classes, for example genetic, proteomic and metabolomic. The interpretation of these diagnostic tests will require mathematical algorithms able to identify signatures characteristic of different disease strata.

To address these findings, the review sets out a vision that the UK will provide an optimal environment for the discovery, development and adoption of innovative molecular pathology tests, enhancing the benefits of stratified medicine for patients to deliver clinical, economic and research benefits.

In order to deliver this, the review steering group recommended consideration of three issues – path, proximity and people.

Path

A clear map of the diagnostic development path should be produced, including the evidence needs of the regulatory, evaluation and commissioning organisations along the path. Consideration should also be given to whether these organisations provide appropriate coverage and support.

Proximity

The research base, pathology services and industry have become separated, to the detriment of all. These parties should be brought back into closer proximity.

People

The skills base of the UK should be enhanced, by developing future research.

Find more information in the MRC stratified medicine strategy workshop report (2013).

Why we're doing it

Precision medicine, or stratification, underpinned by a sound understanding of disease, will enable us to pinpoint novel targets for the development of new treatments and biomarkers that tell us more about disease progression and response to treatment within appropriate patient groups.

Past projects, outcomes and impact

Precision medicine consortia

MRC’s precision medicine initiative has drawn on experience gained through investment in three pilot consortia under MRC and the Association of the British Pharmaceutical Industry (ABPI) inflammation and immunity initiative:

  • chronic obstructive pulmonary disease (COPD)
  • rheumatoid arthritis
  • diabetes.

This initiative brought together industry and academic experts – covering basic, clinical and therapeutic development research – to develop disease-focused consortia addressing the challenges of disease stratification and biomarker identification:

  • COPDMAP – the COPD MRC and ABPI partnership (Professor Chris Brightling, University of Leicester)
  • RA MAP – the rheumatoid arthritis consortium (Professors Andrew Cope and John Issacs, King’s College London and Newcastle University)
  • MASTERMIND – MRC and APBI stratification and extreme response mechanism in diabetes (Professor Andrew Hattersley, University of Exeter).

Precision medicine consortia awards

In addition to the three pilot MRC and ABPI programmes, MRC is supporting a further 14 precision medicine consortia focusing on:

  • rheumatoid arthritis – in partnership with Arthritis Research UK
  • hepatitis C
  • a rare genetic condition called Gaucher’s disease
  • the liver disorder primary biliary cholangitis – formerly known as primary biliary cirrhosis
  • schizophrenia
  • psoriasis
  • hypertension – in partnership with British Heart Foundation
  • systemic lupus erythematosus
  • colorectal cancer – in partnership with Cancer Research UK
  • refractory asthma
  • juvenile idiopathic arthritis – in partnership with Arthritis Research UK
  • prostate cancer – in partnership with Cancer Research UK
  • alcoholic hepatitis
  • idiopathic nephrotic syndrome and chronic kidney disease.

The 14 Precision Medicine Consortia were:

  1. MATURA – maximising therapeutic utility for rheumatoid arthritis using genetic and genomic tissue responses to stratify medicine (Professors Anne Barton and Costantino Pitzalis, University of Manchester and Queen Mary, University of London)
  2. STOP-HCV – stratified medicine to optimise treatment for hepatitis C virus infection (Professor Ellie Barnes, University of Oxford)
  3. GAUCHERITE – predictive measures to stratify clinical outcomes in children and adults with Gaucher disease and responses to specific therapies (Professor Tim Cox, University of Cambridge)
  4. UK-PBC – stratified medicine in primary biliary cirrhosis: understanding disease mechanisms and targeting therapies (Professor David Jones, Newcastle University)
  5. STRATA – schizophrenia, treatment resistance and therapeutic advances (Dr James MacCabe, King’s College London)
  6. PSORT – psoriasis stratification to optimise relevant therapy (Professor Chris Griffiths, University of Manchester)
  7. AIM-HY – ancestry and biological informative markers for stratification of hypertension (Professor Phil Chowiencyzk, King’s College London)
  8. MASTERPLANS – maximising SLE therapeutic potential by application of novel and stratified approaches (Professor Ian Bruce, University of Manchester)
  9. S-CORT – stratification in colorectal cancer: from biology to treatment prediction (Professor Tim Maughan, University of Oxford)
  10. RASP-UK – United Kingdom refractory asthma stratification programme (Professor Liam Heaney, Queen’s University, Belfast)
  11. CLUSTER – childhood arthritis and its associated uveitis; stratification through endotypes and mechanisms to deliver benefit (Professor Lucy Wedderburn, University College London)
  12. Re-IMAGINE – the exploitation of a novel image-based risk stratification tool in early prostate cancer (Professor Mark Emberton, University College London)
  13. Minimalising mortality from alcoholic hepatitis (Professor Mark Thursz, Imperial College London)
  14. NURTuRE – changing the landscape of renal medicine to foster a unified approach to stratified medicine (Professor Moin Saleem, University of Bristol)

Molecular pathology nodes

In 2015 MRC and EPSRC funded six molecular pathology nodes, with a total investment of £16 million. Each node is a multidisciplinary centre of innovative molecular diagnostic test discovery and development bringing together the research base, pathology and genetic NHS services and industry.

The six nodes were based at Edinburgh (St Andrews), Glasgow, Leicester, Manchester, Newcastle and Nottingham.

Who to contact

Ask a question about the programme

Email: precision.medicine@mrc.ukri.org

Last updated: 18 October 2022

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