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Research

Multimorbidity / multiple long-term conditions (MLTC)

Summary

Multimorbidity – defined as the co-existence of two or more chronic conditions in a single individual, including mental and physical conditions and long duration infectious diseases – is increasing, both in absolute terms and relative to single diseases, and is associated with a reduction in quality of life, increased use of health services and reduced life expectancy. Research on multimorbidity has been identified as an urgent priority for the UK and globally and is one of the seven health focus themes outlined in the MRC’s Delivery Plan 2019. We are seeking to support and develop research in this important field and work closely with Councils across UKRI, other funders and stakeholders to facilitate the advance in this complex multi-disciplinary area. 

Content

Background

Around one in four people have two or more serious long-term conditions (according to a study by the Health Foundation). This proportion is considerably higher, reaching two thirds, in people aged 65 years and over. The scale of the multimorbidity burden and challenges it poses to the healthcare system require research across different settings and communities to better understand the causes of multimorbidity and to develop new ways to manage and treat multiple conditions.

In 2018, the Academy of Medical Sciences (AMS) published an international policy report evaluating the growing issue of multimorbidity as a global health challenge. The report summarised the existing evidence around multimorbidity and identified the following priorities for multimorbidity research:

  • What are the trends and patterns in multimorbidity?
  • Which multimorbidity clusters cause the greatest burden?
  • What are the determinants of the most common clusters of conditions?
  • What strategies are best able to facilitate the simultaneous or stepwise prevention of chronic conditions that contribute to the most common multimorbidity clusters?
  • What strategies are best able to maximise the benefits and limit the risks of treatment among patients with multimorbidity?
  • How can healthcare systems be better organised to maximise the benefits and limit the risks for patients with multimorbidity?

Following the report, the Academy, MRC, the National Institute for Health Research (NIHR), and Wellcome agreed to come together to coordinate a 'multimorbidity funders group'. Working alongside other charities, this group published a ’cross-funder multimorbidity research framework' in June 2020, with the goal to help funders coordinate their efforts and initiatives, engage with each other and to collectively reach out to their different research communities facilitating broader academic involvement.

Activities

Workshop “Multimorbidity: Cross-sector opportunities for developing new interventions for patients with multiple long-term conditions” (October 2020)

This Academy of Medical Sciences’ FORUM workshop, held in partnership with the MRC and NIHR, explored cross-sector approaches to harnessing new understanding of disease clustering, underlying biological pathways and clinical trials methodology to develop new effective interventions for patients with multimorbidity.

Workshop “Advancing research to tackle multimorbidity: the UK and LMIC perspectives” (June 2018)

The Academy of Medical Sciences, MRC, NIHR, and Wellcome hosted a joint two-day workshop that explored key research priorities in the field in the UK and in the low- and middle-income countries. The workshop provided a platform for discussing opportunities where research could have the most impact in addressing multimorbidity, as well as the enablers and existing barriers of such research, and how the latter could be overcome to improve the evidence-base. The workshop’s report is available here.

How we support research into multiple long-term conditions

Pump-priming calls 2018/2019

Tackling Multimorbidity at Scale – a UKRI initiative in partnership with the NIHR

The £20M Strategic Priorities Fund (SPF) initiative “Tackling multimorbidity at scale: Understanding disease clusters, determinants & biological pathways” jointly funded by the UK Research and Innovation (UKRI) and the Department of Health and Social Care (DHSC), through the NIHR, was launched in 2019 to improve prevention, management and treatment of multiple long-term conditions through building UK’s capacity for transformative research in this area.

We are seeking to develop this new field by moving away from a ‘one-disease, one mechanism’ approach in order to better understand the diverse determinants of multimorbidity, including biological, environmental, psychological and socioeconomic factors, and ultimately unpick and target the common root causes of multiple long-term conditions.

The initiative is delivered by the MRC and NIHR, in partnership with the Economic and Social Research Council, and in collaboration with the Engineering and Physical Sciences Research Council. It supports a network of multi-disciplinary Research Collaboratives that will utilise and build on the UK’s strength in having well-powered population and clinical cohorts and datasets with extensive patient phenotyping and stratification to capture and interrogate the dynamic disease-disease interactions and to identify points of intervention to prevent the development of multimorbidity and better manage conditions for patient benefit.

Researcher-led applications to MRC research boards and panels

Research into multiple long-term conditions (multimorbidity) is funded across our boards and panels where it fits their remits and applications can be submitted to our regular calls, including by MRC boards:

Please note that multimorbidity is an opportunity area for our Population and Systems Medicine Board, which supports research related to the physiology and pathophysiology of all the major organs and systems.

Research projects are also eligible for all our training investments. More information about training grants, specifically with respect to fellowships and studentships is available at our Skills & Careers pages.

Supported Studies

The SPF “Tackling Multimorbidity at scale” Initiative

The SPF programme “Tackling multimorbidity at scale: Understanding disease clusters, determinants & biological pathways” supported six collaboratives.

Wave 1 awards (PDF, 25KB):

Multimorbidity Mechanism and Therapeutics Research Collaborative (MMTRC). This collaboration between UCL, University of Cambridge, University of Bristol, University Hospitals Birmingham and University of Liverpool is being led by Professor Aroon Hingorani, University College London, and will focus on uncovering common mechanisms underlying diverse diseases. Professor Hingorani said: “The MMTRC seeks to better understand the causes of multiple conditions in the same patient to aid the development of new and optimise use of existing medicines to improve patient care. We will use and compare findings from different large national and international data resources including linked NHS electronic health records, UK Biobank, as well as data from genetic studies and clinical trials to ensure our findings are as reliable as they can be. Patient and public perspectives have had a substantial influence on the planning and development of the programme and will play a central part in all the research activities, as well as the communication and dissemination of the findings.”

ADMISSION UK: Multimorbidity Research Collaborative on MLTC in Hospital: from burden and inequalities to underlying mechanisms. The study, led by Professor Avan Aihie Sayer, Newcastle University, brings together scientists, clinicians and patients from five UK universities and hospitals (Newcastle, Birmingham, Manchester Metropolitan, University College London and Dundee) to transform understanding of multiple long-term conditions in hospital patients. Professor Sayer said: “Living with multiple long-term conditions, also known as multimorbidity, is very common among people admitted to hospital. These patients often stay in hospital for longer, are more likely to die and, for patients who recover, this may take much longer. However, the way that care is delivered in hospital is not ideal; in a system that was designed for the treatment of single conditions, the care of patients with multimorbidity can be unsatisfactory, inefficient and expensive. To date there has been little research on multimorbidity in hospital patients which is crucial to understand how services need to be changed.

Harnessing the power of ‘big data’ from routinely-collected hospital, primary and social care records, along with research studies such as UK Biobank and the Scottish Health Research Register (SHARE), ADMISSION will use cutting-edge data science, computing and statistical techniques, care pathway analysis, qualitative methods, genetic epidemiology and phenotypic characterisation. This will enable identification of clusters of long-term conditions in hospital patients, the occurrence of inequalities, the biological causes underlying these clusters, and their consequences. ADMISSION will lay foundations for new approaches to the recognition and treatment of multimorbidity in hospital and inform the design of future care, with potential to improve health outcomes for the millions of patients with multimorbidity admitted to hospital each year.”

Consolidator grants:

Eleven groups were awarded 6-month developmental Consolidator grants to help them develop and test their approaches, acquire preliminary data or expand the expertise of the team. The list of the supported projects could be downloaded here.

Wave 2 awards (PDF, 134KB):

Multimorbidity and Pregnancy: Determinants, Clusters, Consequences and Trajectories (MuM-PreDiCT). The study is being led by Dr Krishnarajah Nirantharakumar, University of Birmingham, and brings together clinicians, researchers and patients’ groups from all four UK nations to address an important clinical problem of multiple long-term conditions in pregnant women. Dr Nirantharakumar said: “Having two or more long-term health conditions may make pregnancy more challenging for women. With women at the heart of our research, MuM-PreDiCT aims to use data-driven research to characterise and understand what makes having two or more long-term conditions more likely for pregnant women and the consequences for mother and child; and to predict and prevent adverse outcomes. We will use data from routine health records and birth cohorts from all four nations in the UK and European registries of congenital anomalies to study how health conditions accumulate, how combinations of medications are used in pregnancy, quantify how having multiple conditions and medications affect pregnant women and their children, and predict the chances of developing long-term conditions following pregnancy complications. This will provide valuable information to help women and clinicians make informed decisions and identify points for prevention and intervention. We will also explore the experiences of maternity care for women with two or more long-term conditions and work with families and health/social care professionals to produce recommendations on how to plan and design services that meet the needs of women and their families before, during and after pregnancy.”

Genetic Evaluation of Multimorbidity towards INdividualisation of Interventions (GEMINI). This international collaborative, led by Professor Timothy Frayling, University of Exeter, is focusing on mechanistic research uncovering new genetic links between causally related multiple long-term conditions aiming to advance individualised treatment approaches. Professor Frayling said: “The GEMINI collaborative brings together experts in multimorbidity in primary and secondary care, statisticians, geneticists and patients to tackle the complex problem of multimorbidity using a new approach. This group of researchers, headed by a team in Exeter, but also including those in Oxford, East Anglia and Barcelona, aim to identify new biological links between long-term conditions such as type 2 diabetes, osteoarthritis, asthma and dementia. These conditions are just some of the estimated 50-60 long-term conditions that are most common and cause the greatest burden on the NHS and patients’ quality of life. The new approach involves taking genetic information about each of these 50-60 conditions to establish potential new causal pathways. There may be several types of pathways. Some pathways may be as simple as one disease leading to another, for example, does the joint pain of osteoarthritis lead to weight gain and metabolic disease? Other pathways may be more complex, such as genes being switched on in specific cell types leading to several conditions. We will combine the information from genetics with that from patients’ medical records to understand the consequences of new combinations of risk factors and conditions. Patients with multimorbidity will be involved in the research throughout, especially when deciding which are the most debilitating consequences of multimorbidity.”

Physical and mental health multimorbidity across the lifespan (LIfespaN multimorbidity research Collaborative (LINC)). The LINC collaborative network, led by Professor Marianne Van den Bree, Cardiff University, includes investigation of population-based cohorts that span childhood, adolescence and different stages of adulthood taking into account ethnicity, sex and socioeconomic factors. Professor Van den Bree said: “Physical and mental health disorders frequently occur together and, when they do, are associated with poorer outcomes. Our aim is to understand how such multimorbidity develops over the lifespan. This will enable us to identify those at risk before multimorbidity sets in and to work with others to develop tailored early interventions. A particularly common example of physical and mental health multimorbidity is internalizing disorders (anxiety and depression) co-occurring with cardiometabolic diseases (such as type 2 diabetes and cardiovascular disorder). Our multidisciplinary LIfespaN multimorbidity research Collaborative (LINC) combines investigators from the universities of Cardiff, Bristol, Leeds, Queen Mary London, Exeter and the Wellcome Sanger Institute and Mental Health Services Capital Region of Denmark. LINC aims to study the development of multimorbidity between internalizing and cardiometabolic disorders across the lifespan. We have brought together five large longitudinal population-based cohorts including three young cohorts and four adult cohorts. Our cohorts contain rich data on health and social environment, early-life factors and genomics.  This resource is ethnically and socioeconomically diverse, allowing investigation of the reasons for population differences in multimorbidity development. We will examine the effects of key shared genetic factors, including common (polygenic scores for relevant traits) as well as rare genetic variants. We will investigate the role of neurodevelopmental disorders (such as intellectual disability, ADHD, and autism) and childhood adverse experiences (such as deprivation and maltreatment) on the development of multimorbidity. We will disseminate rapidly to the research community, and work in concert with policymakers to develop multiple-stakeholder interventions to better support those at elevated risk of multimorbidity between internalizing and cardiometabolic disorders.”

DEfining MechanIsms Shared across mulTI-organ FIbrosis to prevent the development of long-term multi-morbidity (DEMISTIFI-Multimorbidity). This academic-industry collaborative led by Professor Jenkins, Imperial College London, aims to uncover etiological mechanisms of multi-organ fibrosis in order to prevent the development of multimorbidity. Professor Jenkins said: "Visceral fibrosis occurs in various organs, consequential to many common diseases, dramatically altering the function of affected organs and leading to 30% of deaths worldwide. Environmental risk factors for fibrosis include smoking, alcohol, obesity, and infectious diseases such as COVID-19. Genetic risk factors also promote fibrosis and impact how people respond to environmental risk factors. It is likely that distinct combinations of genetic and environmental risk factors lead to clusters of fibrotic diseases. The DEfining MechanIsms Shared across mulTI-organ FIbrosis (DEMISTIFI) consortium aims to identify fibrotic clusters, termed Fibrotic Multi-Morbidity (FMM), and to understand how the fibrosis develops in each organ and why it gets progressively worse. Magnetic Resonance Imaging (MRI) will be used to measure fibrosis in different organs and generate a Total Body Fibrosis Score, enabling the identification of early disease and the development of progressive fibrosis both within and across organ systems. We will also use large general population and organ-specific datasets to identify clusters of FMM. The DEMISTIFI consortium will use these data to develop therapeutic strategies for fibrosis before it leads to established disease in multiple organs, thus preventing multiple long-term problems."

Pump-priming call Multimorbidity in the UK population: understanding disease clustering

This joint MRC-NIHR call aimed to pump-prime research that would systematically identify or explore common disease clusters, their distributions in diverse groups and explore multimorbidity trajectories across the life course. Five projects were supported through this call (download the list).

GCRF Global Multimorbidity – Seed-funding

The GCRF global multimorbidity seed-funding call was an MRC initiative developed in collaboration with Wellcome, NIHR, and AMS. The call supported seed-funding projects seeking to develop and test innovative ideas, foster interdisciplinary collaboration, build capacity, and lay the groundwork for future large-scale activity aimed at understanding and tackling multimorbidity in LMICs. 13 projects were supported through this call (download the list (PDF, 88KB)).

Contact

For any queries or for more information related to multimorbidity, please contact multimorbidity@mrc.ukri.org.