Decompensated LIVER Cirrhosis Research Network

Background:

Liver disease is the 3rd commonest cause of premature death in the UK, and the major burden of morbidity and mortality is due to complications of advanced liver disease (decompensated cirrhosis). Costs to the NHS for liver cirrhosis are estimated to exceed £17 billion annually. Although there have been a number of clinical trials conducted in this population over the last decade, there has been limited impact with no new therapies being successfully translated.

Aim and Objectives:

The overarching aim of De-LIVER is to to establish a nationwide, multi- stakeholder network to address shortfalls in, and improve delivery and impact of, clinical research in decompensated cirrhosis. The specific objectives are:

(i) Establish a prototype multi-stakeholder network to advance cirrhosis research, with emphasis on geographical areas of high disease prevalence or limited research access.

(ii) Co-develop consensus positions on current evidence related to fundamental aspects of UK cirrhosis research, including, but not limited to: a. Nature of, and deficiencies in, research infrastructure for cirrhosis clinical trials

b. Challenges and opportunities for effective partnerships between patients, relatives, clinicians (including trainees), research staff and academics c. Clinical factors affecting research delivery, e.g. variation in (inpatient) care for decompensated cirrhosis d. Clinically important questions of intervention and service delivery to be addressed in the next 5-years.

(iii) Define research priorities, and specific requirements (based on a-d above) for delivery of high-quality, collaborative research within a high-functioning research network. Methods:

Underpinning principles for the network will include: encouraging broad involvement from underrepresented groups, co-design of the network, and reducing barriers to recruitment. The work plan will involve 4 inter-related work packages (WPs).

WP1: Develop a prototype network and co-design consensus topics. An initial prototype of the De-LIVER Network will be established through 2 facilitated, online meetings. We will agree on 4 consensus topics (potentially a-d above), and identify knowledge gaps against these consensus topics. We will also use structured techniques to grow the network.

WP2: Co-develop initial positions on fundamental topics affecting UK cirrhosis research. We will develop questionnaires along the lines of consensus topics (a)-(d), also addressing barriers to research delivery. This will be disseminated as an online survey, with a Delphi process conducted where needed.

WP3: Co-develop consensus positions on these agreed fundamental areas. Facilitated World Cafe´ workshops will be held to gain consensus on the topics identified in WP1 and surveyed in WP2.

WP4: Define research priorities, and specific requirements, for delivery of high- quality research proposals in decompensated cirrhosis. A further virtual workshop will define the consensus research proposal for stage 2 application, and requirements to deliver the research proposal within current UK research infrastructure.

Timeline for delivery: 15 months

Anticipated impact: (i) establish a decompensated cirrhosis network, (ii) develop consensus statements on fundamental issues of UK cirrhosis research, (iii) define high-quality research question for submission to stage 2 proposal, and (iv) increase participation from low-research activity centres.