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19/93 Liver disease commissioning brief



The National Institute for Health Research (NIHR) is interested in receiving research proposals evaluating public health measures, health care interventions and health and social care services to improve the prevention, diagnosis and acute/long-term management of liver disease.

Applicants should justify the importance of their proposed research and identify how the work supports aspirations to reduce health inequalities, improve health outcomes, enable individuals to better manage their own health, extend or support the roles of health and social care staff or improve the delivery of health and social care services. Proposals should also reflect the role of social care in delivering improved outcomes for individuals and the health and social care system. The inclusion of a social care component/outcomes should be included, where appropriate. 

Specifically for the purposes of this call, applicants are encouraged to include geographic populations with high disease burden, which have been historically under served by NIHR research activity in order to ensure that NIHR research is conducted in the areas where health needs are greatest. We would encourage applicants to bring on one or two centres with high disease burden that have been relatively inactive in this area to date.

We would welcome applications that span the remit of one or more of the participating research programmes and which comprise of co-ordinated teams of investigators spanning different specialties/disciplines and geographical centres.  

Applications should be co-produced, demonstrating an equal partnership with service commissioners, providers and service users in order to provide evidence and actionable findings of immediate utility to decision-makers and service users. Applicants may wish to consult the NIHR INVOLVE guidance on co-producing research.

Deadline for proposals:
The deadline for outline applications is 1pm Wednesday 27 November 2019.

A webinar to support applicants will be held on Monday 16 September 2019 at 1:30pm, potential attendees should register their interest at the following email address For support developing applications, applicants are also encouraged to contact their local NIHR Research Design Service (RDS) or equivalent in the first instance. 

Supporting Information
It is estimated that up to 90% of liver disease is preventable yet liver disease mortality has increased by over 250% since 1971 in contrast with mortality from the other major causes of premature mortality (diabetes, cancer, heart disease etc.) which has reduced. [The 2nd Atlas of Variation in risk factors and healthcare for liver disease in England: September 2017]

Notably, there is a nine year gap between the median age at death for patients with liver disease residing in the five most deprived areas compared to those from the least deprived five. Whilst there is a negative correlation between deprivation and age of death, this is even more pronounced for deaths from alcohol-related liver disease where there is a 6 year gap between the five most and least deprived areas.

It can take many years for liver disease to progress to a stage where symptoms develop and/or there is an impact on quality of life, making estimates of the burden of disease in the population difficult. Estimates suggest that between 10-20% of the population of England are potentially at some risk of developing some kind of liver disease during their lifetime and, at any one time, between 600,000 and 700,000 individuals may have a significant degree of liver damage. [The 2nd Atlas of Variation in risk factors and healthcare for liver disease in England]

The Lancet Standing Commission on Liver Disease in the UK recently published its fifth report (Williams et al, 2018) which highlighted the growing burden of liver disease. It also included a financial analysis estimating the full societal costs for alcohol misuse, including crime, lost productivity, and child services to be c£21 billion per year in England and Wales, although this figure could be as high as £52 billion. The report also noted that for obesity, the total cost to society was c£27 billion per annum, with some estimates as high as £45 billion.

Research Following Patient Need
Of note, the locations of NIHR Clinical Research Network (CRN) supported research in liver disease in the UK, as defined by the number of recruiting research studies categorised as ‘hepatology’ since 2010/11, do not map onto regions where liver disease is most concentrated.

The shading in Figure 1A illustrates the number of NIHR CRN supported studies that have recruited participants in each Clinical Commissioning Group (CCG) area in the specialty of ‘hepatology’, while Figure 1B shows the liver disease mortality for individuals aged under 75 mapped by CCG.

Figure 2 indicates that in the North West of England in particular there is significant disparity between liver disease mortality (Fig 2B: areas in red) and number of recruiting studies (Fig 2A), with many of the CCGs there not having recruited to studies.

Figure 1: A: Number of recruiting NIHR CRN supported research studies categorised as ‘hepatology’ in comparison to liver disease mortality for individuals aged under 75 mapped by CCG. (Open Data Platform Research Targeting Tool, NIHR CRN (Accessed 19 June 2019). Data sources: A: NIHR CRN Central Portfolio Management System (CPMS). B: NHS Digital – CCG Outcomes Framework, © Crown Copyright 2019).

Whole of England liver research recruitment and mortality maps.

Figure 2: A map of liver disease mortality (B: areas indicated in red) in the North West of England and number of recruiting NIHR CRN supported studies categorised as hepatology (A). (Open Data Platform Research Targeting Tool, NIHR CRN (Accessed 19 June 2019). Data sources: A: NIHR CRN Central Portfolio Management System (CPMS). B: NHS Digital – CCG Outcomes Framework, © Crown Copyright 2019).

North West England liver research recruitment and mortality maps.


Please note that the enclosed maps are provided to illustrate the potential mismatch between research and burden of disease. The data is derived from the NIHR Clinical Research Network (CRN) in England. The CRN does not have direct responsibility outside of England and currently equivalent data from the Devolved Administrations is not included in the Research Targeting Tool. However, the NIHR is keen to ensure that research is conducted in the areas where health needs are greatest across the UK and therefore, applicants from the Devolved Administrations will also be expected to justify their choice of recruitment sites.        

NIHR Research Development Award
To ensure that NIHR research is conducted in the areas where health needs are greatest, the NIHR is willing to provide a small amount of additional funding to incentivise and support those NHS organisations with limited research activity to undertake high quality research and increase patient participation in NIHR research studies.  Applicants may request up to an additional £10K to support this activity providing clear justification for the need for the award and details of how this additional funding will be used, for example, to ensure protected research time for front line staff. A letter of support from the recipient NHS organisation is required as part of the stage 1 application guaranteeing support for the award and how this would be strategically important to the organisation.  Details of these additional costs and justification should be included in the overall budget as part of the stage 1 application.   

Specific areas of interest for research
For the purpose of this call, several broad themes have been described below with examples of particular areas of interest for research which include the evaluation of both local and National initiatives and all research proposals should address the potential impact on health inequalities and equity of access.

We would particularly welcome applications which address one or more of the eight recommendations highlighted in the Lancet Standing Commission’s fourth report (Williams, 2017).  Applicants may also wish to consider the research priorities identified through the Alcohol-related Liver Disease James Lind Alliance (JLA) Priority Setting Partnership and the Non-alcohol-related liver and gallbladder disorders priority setting partnership in addition to the updated NICE guidance on ‘Alcohol interventions in secondary and further education'.

The following are examples of potential areas of interest for research and do not represent an exhaustive list.

  1. Reducing health inequalities:
    Applications addressing differences in outcomes as well as inequity of access to research.

  2. Identification strategies and engagement between services:
    Strategies to identify patients with liver disease at earlier stages in their natural history, including non-invasive testing and determination of cost-effectiveness
    Evaluation of integrated pathways between primary and secondary care as well as public health and social care including long-term data follow-up and consideration of referral pathways

  3. Behavioural interventions:
    Including brief interventions and use of technology and consideration of the determinations of durability of effect

  4. Management of serious complications of cirrhosis
    Portal-hypertension and ascites
    Acute on chronic liver failure

  5. Organ transplant:
    Studies of machine preservation including determination of cost effectiveness

  6. What to do once liver disease has been identified:
    E.G. delivery of secondary care after admission with liver disease (e.g. care bundle to prevent re-admission)
    Appropriate management in primary care

  7. Non alcohol related fatty Liver:
    Diagnostic tests/biomarkers
    Prevention and management
    Evaluation of new treatments/precision medicine

  8. Hepatitis:
    Identification strategies, particularly in hard to reach groups

  9. Paediatrics:
    Prevention and management of fatty liver
    Management of chronic liver disease(s) including transition to adult services particularly in those with other long term/chronic conditions

How to apply & supporting information:
The Programmes involved in this call are:

Applicants should note that:

  • Proposals must be within the remit of at least one participating NIHR Programme. However, we expect to receive applications which span the remit of one or more programme. To enable applications to be written without concern for individual programme remits or boundaries, applications will be submitted to one cross-programme team, rather than to individual programmes.
  • Patient and public involvement must be included within the application and study design to ensure the research is relevant and appropriate to patients and the public.
  • Ambitious applications consisting of more than one clearly linked work package as well as applications for individual studies will be welcomed. We would also encourage the building of research capacity through the research process. 
  • The participating NIHR programmes fund rigorous, problem-focused research to assess the impact of existing health technologies. Applicants must demonstrate that the proposed methodology is appropriate and robust, with consideration given to methodological limitations. 
  • Applicants should clearly state how their proposed research addresses an explicit evidence gap and how the research adds value to the existing NIHR research portfolio.
  • This call represents an ongoing area of interest for the NIHR and following this opportunity, the NIHR research programmes would still be interested in receiving applications in this area to their researcher-led workstreams.

Contact Information
General questions about the call should be addressed to your local RDS in the first instance or further guidance may be obtained by sending a short summary (max 1 A4 page) of their research proposal, in a structured format including rationale, research question, proposed methodology and outcome/evaluation methods to the following address: