EVenti: The Prognostic Performance of the Enhanced Liver Fibrosis Test in UK Patients with Chronic Liver Disease Assessed 20 Years After Recruitment to the EUROGOLF study (EVenti).

University College London (UCL) requires access to NHS England data for the following research project: EVenti: The Prognostic Performance of the Enhanced Liver Fibrosis Test in UK Patients with Chronic Liver Disease Assessed 20 Years After Recruitment to the EUROGOLF study (EVenti).

The following is a summary of the aims of the research project:

• More than twenty years have now passed since the EUROGOLF study, and this study aims to assess the prognostic performance of the enhanced liver fibrosis (ELF) test, liver biopsy and liver blood tests, and understand the value of ELF and/or blood tests as part of an evaluation of liver disease risk in middle life.

• Understand the incidence of liver-related outcomes including hospital admissions for bleeding varices, ascites, hepatic encephalopathy, liver cancer, liver transplantation and death from liver disease or any cause identified

• Understand the influence of the aetiology of liver disease, age, gender and socio-economic status on outcomes

• Understand the costs associated with chronic liver disease in the UK over the past 23 years.

Between 1998 and 2000 the European Group on Live Fibrosis (EUROGOLF) study recruited 921 patients with mixed chronic liver disease at 13 European centres, including 497 English patients, to identify a new diagnostic test for liver fibrosis.

All those who participated provided a blood sample and a liver biopsy. Over 40 biomarkers of liver fibrosis were evaluated for their ability to detect liver fibrosis stages, which were assessed against the liver biopsy taken at the same time as the blood sample. The study identified and validated a minimal set of 3 markers combined in an algorithm to generate a score known as the ELF test.

Under this Data Sharing Agreement, this study is now a follow up study. The Controller (UCL) have obtained Section 251 support from the Confidentiality Advisory Group (CAG) in order to obtain data in order to address the common law duty of confidentiality.

The following NHS England Data will be accessed:

• Hospital Episode Statistics

o Admitted Patient Care – necessary to answer the research question about the number, date and reasons for admission to hospital during the study period and to determine the health economics of chronic liver disease managed in England.

To identify episodes involving cirrhosis, a severe liver-related complication, primary liver cancer, or varices without bleeding

o Accident & Emergency – necessary because it will allow the study to determine the effectiveness and cost effectiveness of ELF and to address the health economic consequences of chronic liver disease in England.

o Critical Care – necessary because it will allow the study to determine the clinical outcomes and health economic outcomes of participants.

o Outpatients – necessary because it will allow the determination of the health economic consequences of chronic liver disease in England and the effectiveness and cost effectiveness of the Eventi study.

• Emergency Care Data Set (ECDS) – necessary because it will allow the study to determine the effectiveness and cost-effectiveness of ELF and to address the health economic consequences of chronic liver disease in England after 2019/20.

• Civil Registration Mortality – necessary to better understand patient outcomes and cause of death.

• Cancer Registration – necessary because it will allow the study to determine what cancers, if any, the participants developed and whether the ELF test can aid in the prediction of liver cancer.

The level of the Data will be:

• Identifiable – necessary to enable linkage of the data with data collected from other sources, including the participants themselves.

The Data will be minimised as follows:

• Limited to a cohort of 497 individuals who were recruited in English Centres that participated in the original EUROGOLF study.

• Limited to data between 1998 until the 23rd annual anniversary of each individual’s date of inclusion into the study. With respect to Cancer Registration Data and Civil Registrations of Death, this will be limited to the latest available at the time of dissemination.

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

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

Amazon Web Services provides IT hosting services that support the UCL Data Safe Haven and will store the Data as contracted by UCL.

Data will be accessed by:

A PhD student enrolled with University College London. The individual has completed mandatory data protection and confidentiality training and is subject to University College London's policies on data protection and confidentiality. The individual accessing the data will do so under the supervision of a substantive employee of University College London. University College London would be responsible and liable for any work carried out by the individual. The PhD student would only work on the data for the purposes described in this Data Sharing Agreement (DSA).

A Public and Patient Involvement and Engagement group helped refine the purpose of the research. The group strongly supported the collection of the data for the purposes described above, believing this to be in the overwhelming interests of patients and the public and in accordance with the purpose of the original EUROGOLF study to discover accurate biomarkers of liver disease prognosis.

UCL are aiming to assess the prognostic performance and cost effectiveness of the enhanced liver fibrosis (ELF) test. The ELF test is a commercial product that is available to be purchased. As a result of the findings from the Eventi research study, there is a possibility that the ELF test may benefit from the publicity of the findings which may result in increased purchases.

UCL will transfer data to NHS England. The data will consist of identifying details, specifically: NHS Number, Date of Birth, Gender and a unique person ID. This will allow for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the HES/ECDS, Deaths and Cancer Registration datasets to the recipient. 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.

Once received, the requested data will be uploaded to the UCL Data Safe Haven. Amazon Web Services (AWS) is a processor acting under the instructions of UCL. AWS’ role is limited to secure backup of data stored in UCL’s Data Safe Haven. UCL uses offsite data centre services provided by VIRTUS data centre. VIRTUS does not have access to the data.

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

The Controller 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).

Remote processing will be from secure locations within England. The data will not leave England at any time.

Access is restricted to substantive employees or agents of UCL who have authorisation from the Principal Investigator.

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

The Data will be linked at the person record level with data collected during the original EUROGOLF study.

Researchers from UCL will process the Data for the purposes described above.

The expected outputs of the processing will be:

• Submissions to peer reviewed journals. It is anticipated that at least two publications will be submitted within 12 months of receipt of the data from NHS England.

• Presentations to the original participating sites in England that participated in EUROGOLF so that the results can be disseminated to colleagues and patients in the year following completion of the data analyses.

• Presentations at the British Association for the Study of the Liver annual meeting, the European Association for the Study of the Liver annual meeting and the American Association for the Study of the Liver meeting in the cycle of the year following completion of the analyses.

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

• Journals

• Social media

• Posters displayed at appropriate conferences.

• Press/media engagement

• Public promotion of the research via the UCL webpages and the study’s own webpages

Outputs will be produced from ~ six months post receipt of the data, and will be produced on an on-going basis.

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 health care users relevant to the subject matter of the study.

Chronic liver disease is the third most common cause of death in the UK. In all cases, liver injury leads to liver fibrosis that accumulates to cause cirrhosis which may lead to fatal complications including liver failure and liver cancer. Liver fibrosis does not cause symptoms and is silent in most cases until complications of cirrhosis develop. At this point treatment is often too late.

New tests have recently made it possible to detect liver fibrosis before serious irreversible harm has developed. The EUROGOLF study set out to identify a blood test that could assess liver fibrosis without the need for a liver biopsy (inserting a needle into the liver). Through the EUROGOLF study, The Enhanced Liver Fibrosis (ELF) test was discovered through the examination of blood samples obtained from 921 patients with chronic liver disease between 1998 and 2000, including 457 patients in the UK. Twenty years after the initial recruitment of this cohort UCL want to determine the long-term prognostic performance of the ELF test.

This work may:

• Better inform those planning health services and programmes for those with liver cirrhosis

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.

Measures will be taken to attempt to disseminate the results to the general public through press releases to major media outlets including the print press and radio and television journalists. The British Liver Trust is aware of this work and will be informed of the results, along with the British Liver Alliance.

Yielded Benefits is not a requirement for new applications.