Equity of access to liver transplantation in the UK (EquiLT-UK): impact of socio-demographic characteristics on registration, organ offering, allocation and transplant outcomes.

NHS Blood and Transplant (NHSBT) requires access to NHS England data for the purpose of the following research project:

Equity of access to liver transplant in the UK (EquiLT-UK): impact of socio-demographic characteristics on registration, organ offering, allocation and transplant outcomes

The project will be conducted in relation to a PhD qualification at University College London. The burden of liver disease is worryingly increasing and data from 2019 estimate that liver cirrhosis is amongst the top 3 causes of death in people between 30- and 60-year-old in the UK (World Health Organization, WHO 2019). Liver transplantation (LT) remains today the only cure for end stage liver disease, therefore it is of utmost importance that equitable access to this life-saving procedure is guaranteed to everyone in need.

However, the LT process is long, selective, and meticulous and barriers can arise at any stage.

Whilst NHSBT has been collecting data about all the patients registered for liver transplantation, the lack of a chronic liver disease database represent an important barrier to understand the need for liver transplantation in the general population.

Usually, use of data for research is obtained by contacting the participants of the study individually to obtain their consent, but for the purpose of this study, it would be impractical to gain individual consent for such large number of participants, especially as many of this cohort would have unfortunately died.

Therefore, since these data are routinely collected and stored within NHS England, the request is for a list of all patients admitted to English hospitals with liver disease, diagnosed with liver cancer or died of liver disease in the past 20 years.

This is because the history of liver transplantation has been affected by 2 major events: the introduction of the United Kingdom Model for End-Stage Liver Disease (UKELD) score and Local offer allocation in 2008 and the introduction of the Transplant Benefit Score (TBS) and National Liver Offering Scheme (NLOS) in 2018. These two changes in transplant practice would have inevitably affected access to LT and the aim is to capture the changes that have occurred in 3 eras of transplantation: 2004-2008 / 2008-2018 / 2018-2024.

The following is a summary of the aims of the research project provided by or on behalf of NHSBT:

To identify in patients with liver disease the incidence of waiting list registrations, organ offers, transplantations, waiting list mortality and graft/patient survival post-LT, as stratified by sociodemographic factors (including age group, sex/gender, race/ethnicity, SES, and aetiology of liver disease)

The aim is to establish if the demographics and social status of patients who successfully receive a LT are reflective of the ones in need or if they represent a privileged elite. It is an opportunity to assess the fairness of the transplant process, to evaluate different allocation systems over the years and to explore how the COVID pandemic has impacted patients' selection and survival.

This observational study is a retrospective cohort study. It will be divided into three main phases, each linked to a project objective and following a quantitative research design.

1. Phase 1: Analysis of the Waiting List outcomes

Objective: To describe the graft offers and the clinical outcomes of the patients registered for a liver transplant by their sociodemographic characteristics. These will be assessed according to different allocation models and type of registration, with subanalyses by country of registration.

2. Phase 2: Analysis of post-LT outcomes by the main axis of inequalities

Objective: To describe the post-liver transplant clinical outcomes of the patients who received a liver transplant by their sociodemographic characteristics. These will be assessed according to different allocation models, urgency of registration, with subanalyses by country of registration and COVID pandemic status and adjusted by donor factors.

3. Phase 3: National evaluation of the need for liver transplantation in the general population – Access to the Waiting list

Objective: To estimate the need for LT in the general population using a sample of patients available from national databases and to describe the impact of sociodemographic characteristics on the likelihood of being (or not) registered on the liver transplant waiting list.

The following NHS England Data will be accessed:

• Hospital Episode Statistics Admitted Patient Care – necessary to identify patients with indications for liver transplantation and those who had contraindications (for example who were elderly, frail, with dementia, with widespread cancer, with cancer outside of criteria for transplant).

• NDRS Cancer Consolidated Data Set – necessary to identify patients with indications for liver transplantation and those who had contraindications (for example who were elderly, frail, with dementia, with widespread cancer, with cancer outside of criteria for transplant).

• Civil Registrations of Death– is required to identify those who met the criteria for transplant (as established from previous 2 datasets) but were not registered for one (not linked to the UK transplant registry) and died without transplant. This enables the study team to estimate the gap between need and transplants provided.

The level of the Data will be;

• Identifiable – Although pseudonymised data is required back from NHS England, the data (regarding individuals that appear in the United Kingdom Transplant Registry (UKTR) cohort only) still classifies as identifiable as the technical ability to re-identify the NHS England data with the UKTR identifiers remain.

The Data will be minimised as follows:

• Limited to a study cohort identified by NHS England as meeting the criteria: Adults aged 17 years and above, with a recognised indication for liver transplant, during the study period 2004-2024.

• Limited to data between April 2004 – March 2024

• Limited to conditions relevant to the study identified by specific ICD-10 codes provided by NHSBT to NHS England in the range between B15-B19, C22, I81, I85, between K70- K77, plus additional rare disease (E83.0, E83.1) OPCS-4 codes; describing Patients in need for LT" (chronic liver disease with decompensation, end-stage liver disease, liver cancer, etc. Amendments to these codes will be considered based on clinical appropriateness.

• Limited to the following geographic area of England.

NHSBT is the research sponsor and the controller as the organisation 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.

The study is in the public interest because it aims to produce information to guide future decisions over patients’ care. NHSBT is a Health and Social Care Institution and as such will be making the results publicly available and promote changes of public health interest.

The funding comes from multiple sources. Funders include:

• NHSBT – Funding is in place until September 2026.

• Royal Free Charity – Funding is in place until September 2026.

Additional costs related to data requests that cannot be covered by NHSBT, will be supported by the Royal Free Charity (Special Purpose Fund).

The funders will have no ability to suppress or otherwise limit the publication of findings.

Data will be accessed by two individuals, the Principal Investigator and Senior Statistician who are both substantive employees of NHSBT.

Patient and Public Involvement and Engagement (PPIE) activity has been sought through the NHSBT PPIE team, to inform the design, implementation, and outputs for this project.

The NHSBT PPAG (Patient and Public Advisory Group) includes people at all stages of the transplant continuum and their relatives or carers. They represent a heterogenous group of different age, gender, ethnicity, socio-economic status and include individuals with disabilities.

A call for participation has been sent out and members of the NHSBT PPAG had the opportunity to express their interest. Two individuals were selected as part of the Steering Committee to review the research protocol and attend an introductory meeting with the CI. Following this, at least one of them will be required every 6 months for 1-hour meetings to discuss progress and provide feedback. The Project Steering Group has exclusively an advisory role.

Further PPAG support has been sought in the form of focus groups within NHSBT PPAG. 30mins were allocated to the CI to explain the research aims and plan. 1hour time was reserved for participant’s feedback, comments and question.

As a result of the feedback (verbal and written) obtained by the focus group meetings, the following recommendations were acknowledged and implemented:

• Additional discussions took place to clarify that NHS England data of participants who did not apply for NDOO and are not on NHSBT databases will still be included in the study in pseudonymised form in phase 3 of the study (will affect English patients only). A Data Privacy Notice was written and edited by members of the PPAG with experience in patients’ communication and health literacy.

Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

The NHSBT research team will transfer a list of ICD-10 and OPCS-4 codes describing "Patients in need for LT" (chronic liver disease with decompensation, end-stage liver disease, liver cancer, etc.) and will request NHS England to retrieve all patients matching those diagnosis in the past 20 years on 3 linked datasets: HES-APC, NDRS Cancer Consolidated Data Set and Civil Registration of Death.

This will represent the core group of participants of the study and will be referred to as the "Denominator database".

Alongside this, NHSBT research team will create an extract derived from the central UKTR database, containing data specifically of the patients registered for liver transplantation during the study period, including each participant’s NHS number, date of birth, gender, and postcode (patients’ identifiers) and their liver waiting list Recipient ID number (UKTR Recipient ID). This extract will contain no clinical data and will be sent electronically and securely via Secure Electronic File Transfer (SEFT) to NHS England, where it will be linked to the Denominator database.

At this point, the entire linked database (Denominator + UKTR) will be pseudonymised. NHS England will create a randomly generated study ID for each participant on the denominator database. For participants on the UKTR the corresponding UKTR Recipient ID will be included prior to returning the full database to NHSBT.

NHS England will provide the relevant records from the following datasets to NHSBT.

• Hospital Episode Statistics Admitted Patient Care (HES APC)

• Civil Registrations of Death

• NDRS Cancer Consolidated Data Set

The only Data which will be identifiable from NHS England are NHSBT patients on UKTR as the extract received from NHS England will contain the UKTR Recipient ID. For patients who are not on the UKTR no identifiable data will be included.

The Data will not be transferred to any other location.

NHSBT will store Data on the NHSBT secure servers only, any Data back ups that are made will be stored on NHSBT secure servers.

The Data will be accessed by authorised personnel via remote access.

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).

Access is restricted to individuals within the Statistics and clinical Research Team at NHSBT who have authorisation from the Principal Investigator. All such individuals are substantive employees of NHSBT

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

The only linkage that will be performed after the NHS England extract is received, is the linkage of clinical information to those UKTR patients whose NHS numbers, recipient ID, date of birth and sex were sent to NHS England for linkage. For this reason, it was requested that NHS England keep recipient IDs on the extract.

No other datasets will be linked.

No data will be added to patients who were not on the UKTR list sent by the investigators to NHS England.

The following information regarding, Opt-Outs will be available on the patient information privacy sheet and will be published on the NHS Blood & Transplant Research Projects Page https://www.nhsbt.nhs.uk/research-and-development/current-research/research-projects/ where both national opt out and study specific opt outs apply.

National Opt-Out: “If you’ve already opted out of having your NHS data used for research, we

won’t use your data. You can also visit the NHS website to opt out, if you haven’t already:

https://www.nhs.uk/your-nhs-data-matters/”

Study-Specific Opt-Out "If you’re okay with your NHS data being used for other studies but not this one, you can contact the lead researcher, and your data will be removed from this study. However, if you live in England, please be aware that your hospital information is still routinely collected by NHS England and may be included in the analysis without your name (pseudonymised). If you’re not happy with this, you can opt out of NHS data sharing (www.nhs.uk/your-nhs-data-matters) and then opt back in after the study ends. This only applies to people living in England. No hospital data will be used from Scotland, Wales, or Northern Ireland." This opt-out is relevant to participants in the UKTR cohort”.

No identifiable data will be used for non NHSBT patients. For NHSBT patients, identifiable data will be stored separately, and no attempts will be made to re-identify individuals, unless the study PI receives direct opt-out notification from those individuals as stated above. In that case identifiable data will be used to retrieve the patients’ information and remove them.

The personal data that will be retained by the research team will be restricted to the minimum necessary to perform the analysis and include age at admission (no date of birth), Index of deprivation measures (no postcodes), month/year of death (no full date of death).

The database will be kept at NHSBT for the minimum time estimated to be necessary to undertake statistical analyses, in accordance with the retention period established in the NHS Records Management Code of Practice for 2023. This time should not exceed 3 years. Once the analyses will be completed, the de-identified data will be archived for additional 2 years and finally safely deleted by 5 years from their acquisition. NHSBT cyber security team will witness deletion of the data and sign the data destruction document, there will be a video recording of this as confirmation.

There will be no requirement and no attempt to re-identify individuals when using the Data.

The expected outputs of the processing will be:

• Submissions to peer reviewed journals Hepatology, Liver Transplantation, Frontline Gastroenterology, one submission per year.

• Presentations at British and European Associations for Study of the liver (BASL and EASL) between May and September 2025/26, Royal Society of Medicine (January 2026) International Liver transplant society (ILTS), European society of organ transplantation (ESOT). The dates for presentations are dependent on when the data is received from NHS England.

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 dataset(s) from which the information was derived.

The findings from this study will be presented in accordance with guidelines presented in the STROBE statement for observational studies (Strengthening the Reporting of Observational Studies in Epidemiology, 2023).

Channels for dissemination will include academic journals, workshops, professional newsletters, social media, Royal Free Charity channels, public promotion of the research and meetings, such as the British Association for Study of the Liver (BASL), the British Liver Transplant Group (BLTG), the British Transplant Society (BTS), the British Society of Gastroenterology (BSG), the European and American Association for Study of the Liver (EASL and AASLD).

Preliminary data will be presented as abstracts/presentations at conferences within the first 3 years of the project, whilst final data will be submitted for journals publication and disseminated to various channels to members of the public and of different healthcare disciplines (Hepatology, transplant surgery, public health) after completion of the study (3 to 5 years).

The results of this study will address an important evidence gap and will be of direct relevance to patients and their clinicians.

From a public perspective, it will provide transparency in the decision-making around listing and allocation of organs; while from an academic point of view, it will provide evidence about Hepatology care provision across the country of national and international relevance.

Enhancing the understanding of the registration, allocation, transplantation, and post LT care processes will provide progress towards tangible solutions to improve equity of access at each level.

This study will help to identify groups of patients and/or geographic areas that would benefit from additional financial or educational support and will be the starting point for further research into targeted interventions.

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.

• advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations

• 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).

The overarching goal is for equitable access to better clinical outcomes in patients with advanced liver disease, in line with the ambitions of the NHS Long Term Plan (NHS, 2019), the Core20PLUS5 initiative (NHS, 2021) and the NHSBT “Meeting the Need” report (NHSBT, 2021).

The study results will add to the body of evidence required to identify groups of patients and/or geographic areas that would benefit from additional financial or educational support. Therefore, it aims to be a starting point for further research into targeted interventions and policy decisions within the NHS. For example, significant findings generated by this research may suggest a review of the current offering and allocation schemes and promote their equitability.

The British Liver Trust, the Royal Free Charity, as well as NHSBT, have strong patients and public engagement groups, who have been advocating for patients’ perspectives since the infancy of this research proposal and will support the research team in advertising the findings to a wider audience.

Yielded Benefits is not a requirement for new applications.