Enhanced Liver Fibrosis (ELF) test to Uncover Cirrhosis as an Indication for Diagnosis and Action for Treatable Events (ELUCIDATE).

University of Leeds (UoL) and University College London (UCL) require access to NHS England data for the purpose of the following research project: Enhanced Liver Fibrosis (ELF) test to Uncover Cirrhosis as an Indication for Diagnosis and Action for Treatable Events (ELUCIDATE).

The following is a summary of the aims of the research project provided by University of Leeds:

"The purpose of this study is to assess the potential benefits of biomarkers in liver and renal disease (such as being able to detect and treat disease earlier) for patients and the NHS. Biomarkers are naturally occurring substances that can be measured, often in fluids such as blood or urine, and which provide information about a patient and their illness.

"In our study we are interested in 3 particular biomarkers, together called the “Enhanced Liver Fibrosis” or “ELF” test. The ELF test is a blood test that gives information about liver disease.

"The ELF test is being researched to find out whether or not it can be used for the early detection of cirrhosis. A sample of blood will be taken and analysed using the ELF test from patients every 6 months for 30 months. In this study we are trying to find out if using the ELF test to give early warning of liver damage (cirrhosis) can enable us to reduce the risk of developing later major complications of liver disease (like bleeding, liver failure, or cancer).

"The study team requires access NHS England data in order to carry out a long-term follow-up analysis for the trial investigating whether the use of serum markers of liver fibrosis result in patient benefit through improved survival and reduced liver-related morbidity and mortality."

The following NHS England data will be accessed:

• Hospital Episode Statistics

o Admitted Patient Care

o Accident & Emergency

o Critical Care

o Outpatients

• Emergency Care Data Set (ECDS)

• Civil Registration Mortality

• Cancer Registration

These data are necessary to determine the incidence of outcomes in the two arms of the ELUCIDATE trial, to measure the effectiveness of ELF guided management of Chronic Liver Disease (CLD) and to determine the cost-effectiveness of this strategy.

The level of data will be:

• Identifiable – necessary because a specific field (attendance number) is required to enable health economist analysis to see how many GP referrals are made against patients with liver cancer.

The data will be minimised as follows:

• Limited to a study cohort of 1,279 patients who consented to participate.

• Limited to data between 2010/11 to latest available for all study participants. The primary endpoint is time-to-event, where event is a severe liver-related complication. The more events the study are able to capture, the greater the power of the randomized controlled trial. Therefore, UoL & UCL need data sets that cover the time period from when the active trial closed to current period.

UoL is the research sponsor, and UCL is the employer of the chief investigator. Additionally, both UCL and UoL also employ co-chief investigators for this study. Both UoL and UCL 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.

The public interest for processing these data is to establish the clinical outcomes for participants in the ELUCIDATE study 10 years after enrolment in order to determine the effectiveness of using the Enhanced Liver Fibrosis test to detect cirrhosis and initiate interventions to detect and treat portal hypertension and liver cancer.

The funding is provided by the Royal Free Charity and the University of Leeds. The funding is specifically for the study described.

National Institute for Health and Care Research (NIHR) funded the active phase of the study. The funding ended on 31/12/2015. However, UoL is required to provide NIHR with a report of their findings at the end of the study.

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

Amazon Web Services (AWS) is a processor acting under the instructions of UCL. AWS’ role is limited to secure back-up 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.

Microsoft Azure Cloud is a processor acting under the instructions of UoL. Microsoft’s role is limited to secure back-up of data stored in UoL. This is co-managed via an external contract with ANS Group Limited.

Data will be accessed by an academic researcher with an honorary contract with UCL. The individual will act as an agent of UoL at all times under supervision from employees of UoL & UCL.

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. In recognition many of the critical outcomes would not accrue without the active study of 3 years necessitating the of long-term follow-up.

Public and Patient Involvement and Engagement involvement was sought again for permission to complete the long-term follow-up of the original study. PPIE representatives supported the original inclusion of the request for permission to follow up the participants using their NHS numbers to interrogate routine data sources for health and care outcomes. As part of the development of this request, the study obtained support from different PPIE representatives (necessitated due to the passage of time and death of the original PPIE partners).

UoL will transfer data to NHS England. The data will consist of identifying details NHS Number, Date of Birth, Postcode & Study ID for the cohort to be linked with NHS England data.

NHS England data will provide the relevant records from the HES, ECDS, Cancer Registration and Civil Registration Deaths datasets to UoL. The data will contain no direct identifying data items but will contain a unique person ID (study ID) which can be used to link the data with other record level data already held by the recipient.

UoL will extract a subset of the data and securely transfer this to UCL. The level of data to be shared will be pseudonymised, including no participant identifiers.

The UCL Data Safe Haven provides the server infrastructure for UCL. The Data Safe Haven is located across two data centres, both operated by UCL.

The respective datasets will be stored on servers at the UoL and the Data Safe Haven for UCL.

Amazon Web Services provides cloud hosting services to UCL and will store the data as contracted by UCL.

The Clinical Trials Research Unit (CTRU) server infrastructure is split between two geographically diverse datacentres on the main UoL campus. Backups are taken from this infrastructure to a separate on-campus datacentre then replicated to the UoL colocation facility in a commercial datacentre (ANS Group) on the other side of Leeds City centre. A monthly copy of the data is also securely transmitted to the UoL Microsoft Azure tenant and co-managed via an external contract with ANS Group Limited.

The data will be accessed by authorised personnel via remote access. The data will remain on the servers at UoL and UCL at all times.

The data will not leave England and Wales at any time.

Aside from this individual, access is restricted to employees or agents of UoL & UCL who have authorisation from the Principal Investigators.

Bart’s Health NHS Trust is not permitted to access the data.

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

The data will be linked at person record level with HES datasets, Civil Registration Deaths Data and Cancer Registration Data obtained from NHS England.

There will be no requirement and no attempt to reidentify individuals when using the data.

Researchers from the CTRU (based at UoL) and the UCL will analyse the data for the purposes described above.

The expected outputs of the processing will be:

· A report of findings to the ELUCIDATE steering committee at completion of the analyses or at 1-year.

· Submissions to peer reviewed journals within 18 months of the data being provided to the investigators.

· Presentations at the International Liver Congress (European Association for the Study of the Liver) and The Liver Meeting (American Association for the Study of the Liver).

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 – made available through UCL and UoL website

· Social media

· Public reports

· Posters displayed at national and international liver congresses

· Press/media engagement

· Public promotion of the research through NIHR website

· Participant newsletters

· Reports aimed at participants and research collaborators.

The target date for publication of the results of the analysis of the effectiveness of the use of the ELF test to guide management of cirrhosis in CLD (the primary outcome of ELUCIDATE) will be within 18 months of transfer the data from NHS England.

It is hoped the findings of this research study will contribute to evidence-based decision-making for policymakers, 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. The work could potentially inform strategies for the early detection of liver cirrhosis and liver cancer.

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 or conditions such as obesity and diabetes.

• 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.

It is hoped access to the data will enable UoL and UCL to answer the research questions of ELUCIDATE and thus decide if widespread use of the ELF test could help improve the clinical outcomes of patients with CLD.

It is predicted that CLD will cost the NHS over £17 billion in the next 5 years. If use of the ELF test can reduce the morbidity and mortality attributable to CLD then dissemination of this test could lead to significant improvements in health and also reduce spending on treatment for CLD so that funding can be reinvested to treat other conditions.

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.

The British Liver Trust (leading UK liver charity) has been informed of this work and the results will be communicated to them to help disseminate the findings to patient advocacy groups and other specialist liver charities and patients’ organisations.

Yielded Benefits is not a requirement for new applications.