Management of patients with chronic liver disease admitted to hospital as an emergency

London School of Hygiene and Tropical Medicine (LSHTM) and Kings College Hospital NHS Foundation Trust (KCH) require access to NHS England data for the purpose of the following research project: Management of patients with chronic liver disease admitted to hospital as an emergency

The following is a summary of the aims of the research project provided by LSHTM and KCH:

The overall aim is to identify which characteristics of treatments and services for acutely ill people with chronic liver disease (CLD) impact on care processes and outcomes, in order to improve the national organisation and delivery of care for all people acutely ill with CLD.

Specific objectives include:

• Describe critical care use and clinical outcomes after a first emergency admission in patients with CLD.

• Explore the impact of regional clinical networks on referral patterns, by creating “super-spells” for each patient and identifying within this super-spell the hospital of the admission and the hospital trust where most of the care was provided. The configuration and characteristics of these networks will be compared, as will regional and organisation changes in referral patterns as a result of the Covid-19 pandemic.

• Explore the impact of regional, hospital and patient characteristics, and the impact of the Covid-19 pandemic at a hospital and regional level, on critical care use of chronic liver disease patients who had a first emergency admission.

• Explore the regional variation in the use of liver transplantation in the first year after an emergency admission

The following NHS England data will be accessed:

Hospital Episode Statistics:

• Admitted Patient Care/ Critical Care – necessary to describe time trends in acute secondary care for patients with chronic liver disease and its outcomes, including admission to critical care and its duration, clinical condition at critical care admission, proportion of cases for whom critical care was withdrawn, total length of hospital stay, readmission rate, and total time spent in hospital within the first year.

• Outpatients – necessary to describe the impact of coordinated specialist outpatient review after discharge on readmissions, referral for transplantation, and mortality, by comparing the outcomes of patients who are discharged from hospitals that offer coordinated specialist outpatient review with patients from hospitals where this type of outpatient review is not available.

• Accident & Emergency/ the Emergency Care Data Set – necessary to examine short-term outcomes including readmissions and total time spent in hospital.

Civil Registration of Death

The level of the data will be pseudonymised.

The data will be minimised as follows:

· Limited to a study cohort identified by NHS England as meeting the following criteria: all patients older than 18 years (or with missing age) with CLD who were admitted with an emergency hospital admission between 1 April 2018 to latest available data.

LSHTM will further minimise the data by identifying when each individual had their first emergency admission for CLD.

KCH as the research sponsor, and LSHTM as the main collaborator, are joint controllers as the organisations responsible for ensuring that the data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding is provided by National Institute for Health Research (NIHR). The funding is for the programme of work and is not specifically limited to the study described.

The British Liver Trust is involved in the wider project in an advisory capacity only for the patient engagement and dissemination stages, and will have no access to the data or involvement in data analysis.

University of Exeter and King’s College London are involved in social science work packages of the wider project, and will have no access to the NHS England data or involvement in data analysis.

Data will be accessed by:

· Substantive employees of LSHTM

· PhD students registered at LSHTM. Any student working with the data held under this Agreement must have completed relevant data protection and confidentiality training and are subject to LSHTM’s policies on data protection and confidentiality. Any students accessing the data will do so under the supervision of a substantive employee of LSHTM. LSHTM would be responsible and liable for any work carried out by students. These students would only work on the data for the purposes described in this Agreement.

· Individuals holding an honorary contract under the supervision of a substantive employee of LSHTM for the purposes described in this DSA only. LSHTM must maintain records in a single location that cover the following details of each individual given access under an honorary contract:

o Their substantive employer;

o Their role in respect of the purpose for the processing specified in the DSA;

o The start date and end date of the duration in which the Data will be accessed by the individual under an honorary contract;

o The necessity for the Data to be accessed by the person(s) holding an honorary contract, instead of a substantive employee of an organisation named as controller or a processor in this DSA;

o Confirmation that an appropriate contract is in place which follows the relevant guidance and is countersigned by the substantive employer of the honorary contract holder.

Consultation with people with liver disease was undertaken at the very earliest initial planning stages of this project. Informal discussion was first held with people hospitalised with CLD at KCH, and with their next of kin, and following an encouraging response an initial research plan was developed.

Through research partners (the British Liver Trust), an online survey of 57 people with CLD from across the UK was conducted to understand their attitudes to the goals and basic research methods under consideration. This sample was representative of the patients with CLD who would be in the proposed study cohort in respect of age, sex and cause of liver disease. More than 80% had required hospitalisation as a consequence of CLD. More than 90% felt it “extremely important” to understand regional variations in outcome of CLD. More than 90% supported the research and felt it to be addressing an important subject, endorsing the approaches proposed to be utilised, including the use of de-identified linked electronic health records. Thirty-three of the respondents volunteered to join an online patient consultation group for the research project.

A face-to face focus group was then conducted with 19 people who had liver transplant for CLD, many of whom had experienced emergency admission at an early stage of their illness. This group also confirmed support for the proposed research and its methodology.

A patient representative with lived experience of CLD, emergency admission and liver transplant is now a grant co-applicant and member of the research team, as is a representative of a patient organisation, the British Liver Trust (BLT). As members of the research team they will be involved in all stages of the research cycle including prioritising research questions, advising upon and managing the research process and routes to data opt-out, analysing and interpreting the results of research, with a prominent role in dissemination of findings.

A Patient Advisory Group (PAG) is to be recruited that will include people with liver disease and lived experience of drug and alcohol services and homelessness. The PAG will be convened at 6 monthly intervals to consider and advise on research questions, conduct and the actions that should follow its findings, feeding back to the research team.

NHS England will generate a study cohort of patients older than 18 years, or with age missing from the dataset at the time of first admission, with chronic liver disease (CLD), who were admitted with an emergency hospital admission between 1 April 2018 till latest available.

NHS England will provide the relevant records from the Hospital Episode Statistics (HES) Admitted Patient Care (APC), Critical Care (CC), Outpatient (OP) and , alongside the Emergency Care Data Set (ECDS) to the London School of Hygiene & Tropical Medicine (LSHTM).

The data will contain no direct identifying data items but will contain a unique person ID which can be used to link the data with other record level data already held by the recipient. Individuals cannot be reidentified through linkage with other data in the possession of the recipient.

The data will not be transferred to any other location.

The data will be stored on a secure server at LSHTM.

The data will be accessed onsite at the premises of LSHTM, or by authorised personnel via remote access. The data will remain on the servers at LSHTM at all times.

The Controller(s) must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract.

For remote access:

- Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA;

- Access controls granting users the minimum level of access required are in place;

- Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data;

- Multifactor authentication (MFA) is required for remote access;

- Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

- All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

The data will not leave England at any time.

Data will be accessed by individuals with an honorary contract with LSHTM. The individuals will act as an agent of LSHTM at all times under supervision from employees of LSHTM. Aside from these individuals, access is restricted to employees or PHD students of LSHTM who have authorisation from the Principal Investigator or co-PI

King’s College Hospital NHS Foundation Trust (KCH) are only permitted to access anonymised data including information derived from NHS England data. Such datasets will adhere to the relevant small number suppression rules to minimise the risk of individuals being identified.

All personnel accessing the data have been appropriately trained in data protection and confidentiality.

The data will be linked at a person record level with datasets obtained from the Intensive Care National Audit & Research Centre (ICNARC).

The ICNARC data will be intensive care clinical data.

Under DARS-NIC-708052-S1L9J, for the NHS England-derived cohort described above, NHS England will supply the following identifiers to ICNARC for linkage with ICNARC data: NHS number, sex, date of birth, postcode and a unique person ID.

ICNARC will link this cohort to ICNARC data, then pseudonymise the ICNARC dataset before supplying the clinical data to LSHTM.

Researchers from LSHTM will analyse the data for the purposes described above.

The expected outputs of the processing will be:

• Reports and papers:

The research team will contribute to a final research report for the funder (NIHR) detailing research methods, findings and conclusions, including recommendations for practice and an extensive summary for patients and the wider public.

The research team will prepare manuscripts to submit for publication in peer-reviewed academic journals, in line with the research objectives outlined above.

The outputs will not contain NHS England data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the datasets from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• The research team intend to organise an end-of-project workshop to formulate recommendation for practice. Participants of this workshop are expected to include NHS England’s Specialised Commissioning Team (or its relevant successor), the British Association for the Study of the Liver (BASL), the British Society for Gastroenterology (BSG) and the Intensive Care Society (ICS). This workshop is planned to produce messages that fit the research team’s audiences (e.g., patient and public, commissioners, clinicians, regulators and policy makers). The recommendations are intended to be summarised in a report that will be disseminated across all the research team’s stakeholders.

The research team expect to produce policy advice targeting NHS England at national level to the Specialised Commissioners, and at a regional level by engagement with regional medical directors through formal meetings to discuss the findings and inform change at the local commissioning level. In addition to formal commissioning, the research team plan to engage lead hepatologists in NHS Trusts via the BASL and BSG liver networks and ensure they are aware of the findings and the value of introducing change to their organisations.

The research team intend to feed back to The National Institute for Health and Care Excellence (NICE) on findings relating to NICE Pathways on the management of acutely ill patients in hospital, and NICE guidelines on gastrointestinal bleeding, acute kidney injury, complications of cirrhosis, and recognising and responding to deterioration. The research team plan to prepare a training package and associated resources aimed at relevant professional bodies, including the BSG, BASL, ICS, and NHS Blood and Transplant, and which can be used by clinicians and drug and alcohol services to give information, address stigma and improve patient engagement.

The target dates for production and dissemination of the outputs are Q4 2023- Q3 2024.

The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of chronic liver disease (CLD) patients.

The research is expected to provide a better understanding of three interacting complexities: the complexity of CLD and its treatment options, the complexity of the life situation of many CLD patients, and the complexity of the healthcare system. The study’s findings are expected to lead to recommendations about how the services for patients with CLD can be made safer and more effective.

The use of the data could :

· help the system to better understand the health and care needs of populations.

· lead to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience.

· advance understanding of regional and national trends in health and social care needs.

· inform planning health services and programmes, for example to improve equity of access, experience and outcomes.

· inform decisions on how to effectively allocate and evaluate funding according to health needs.

· provide a mechanism for checking the quality of care. This could include identifying areas of good practice to learn from, or areas of poorer practice which need to be addressed.

· support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients.

Patient representatives with lived experience of CLD are members of the research team and will be involved in analysing and interpreting the results of the study, with a prominent role in dissemination of findings.

Recognising patients and the public as key stakeholders in the research, the dissemination plan includes webinars, presentations and reports for patients and patient organisations. Patient representatives will be involved to ensure that all relevant organisations are engaged and that the style and format of publications is accessible to these audiences.

The data provided by NHS England has been used to develop and validate methods to identify first emergency hospital admissions for advanced chronic liver disease (CLD). The methods are published in the open access peer-reviewed journal JHEP Reports: doi: 10.1016/j.jhepr.2024.101322. This is publicly available and includes the full algorithm so that it can be used by other researchers, as well as by the research team in its further research.

The algorithm has been applied to the data provided by NHS England to answer four more research questions so far, as described below.

1. To describe the national time trends in outcome of first emergency admission for CLD. The stark findings of this analysis of more than 80,000 patients have confirmed the need for this project, for earlier diagnosis in primary care and more consistent and effective management in secondary care. A publication describing these findings has been submitted for consideration of publication in JHEP Reports.

2. To further explore regional variation in first emergency admission for CLD. The results of this analysis were presented at the British Association for the Study of the Liver in October 2024. These demonstrated a more than 2-fold variation in incidence of first emergency admission for CLD between Integrated Care Boards across England with markedly higher rates in the North and striking variation in the incidence of specific aetiologies of CLD. The research is being written up as a publication for a peer-reviewed journal.

3. To understand patient, disease and geographic factors in access to liver transplant amongst first emergency admissions for CLD. The results of this analysis were presented at the British Association for the Study of the Liver in October 2025. These demonstrated that only a very small proportion of these patients receive a liver transplant, with stark differences in access by aetiology of CLD, structural factors and region. The research is being written up as a publication for a peer-reviewed journal.

4. To understand survival in first emergency admissions for CLD, according to geography, aetiology and disease severity. The results of this analysis were presented at the British Association for the Study of the Liver in October 2025. These demonstrated that the mortality burden of CLD is exceptional, with differential survival reported across CLD sub-groups and geographic regions. The research is being written up as a publication for a peer-reviewed journal.