BRITISH Study - Using cardiovascular magnetic resonance identified scar as the Benchmark Risk Indication Tool for Implantable cardioverter defibrillators in patients with non-Ischemic Cardiomyopathy and Severe systolic Heart failure.

The University of Southampton (UoS) and University Hospital Southampton NHS Foundation Trust (UHS) requires access to NHS England data for the purpose of the following research project:

BRITISH Study: Using cardiovascular magnetic resonance identified scar as the Benchmark Risk Indication Tool for Implantable cardioverter defibrillators in patients with Non-Ischemic Cardiomyopathy and Severe systolic Heart failure.

The BRITISH study is a prospective multicentre, parallel group, randomised controlled trial (RCT) and an Observational Registry. The BRITISH RCT aims to identify which patients will benefit from having an ICD (Implantable Cardioverter Defibrillator) and which patients are better off not having an ICD. The BRITISH Registry will provide important information on the routine care patients receive in relation to heart failure. The purpose of this Data Sharing Agreement is to provide data for the RCT.

The following is a summary of the objective of the research project provided by the Controllers:

1) Primary objective is to determine, if implantable cardioverter defibrillators (ICD) therapy reduces all-cause mortality compared to no ICD therapy in patients with non-ischaemic cardiomyopathy (NICM), Cardiac Magnetic Resonance Imaging (CMR)-detected ventricular scar, and Left Ventricular Ejection Fraction (LVEF) ≤35%.

2) Secondary objectives are to determine whether an ICD alters the mode of death or rate of non-fatal events, and affects wellbeing

Recruitment is planned over a 36-month period. The target recruitment for the RCT is 1252 participants. Its is expected that ~500 participants will have been recruited when the first data linkage to the mortality data will take place, and annual linkages will take place to include updated cohorts.

The following NHS England Data will be accessed:

• Civil Registrations of Death – necessary to support understanding of whether ICD reduces cardiac-related deaths.

Date of death necessary to assess all-cause mortality to enable the BRITISH Study to determine whether ICD helps reduce mortality rates. Cause of death is necessary to assess sudden cardiac death. In addition, date and cause of death are required to ensure that the incidence of death has been notified correctly to the University of Southampton from the participating NHS sites.

The level of the Data will be identifiable.

The Data will be minimised as follows:

• Limited to a study cohort identified by the University of Southampton;

• Age ≥ 18 years old;

• Diagnosis of NICM on contrast-enhanced cardiovascular magnetic resonance (CMR) imaging with LV scar on routine CMR

University Hospital Southampton NHS Foundation Trust (UHS) is the research sponsor. The Chief Investigator is employed by the UHS and the study is coordinated by the University of Southampton Clinical Trials Unit (SCTU). The UHS and University of Southampton (UoS) are joint Data Controllers and are 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 British Heart Foundation. The funding is specifically for the study described. Funding is in place until March 2029. The funder will have no ability to suppress or otherwise limit the publication of findings.

The BRITISH study has 3 oversight groups that perform the following functions:

• Data Monitoring and Ethics Committee (DMEC) – Safeguard the interests of the trial participants and meet to monitor the outcome measures including safety.

• Trial Management Group (TMG) – Manage the clinical and practical aspects of the study.

• Trial Steering Committee (TSC) – Provide oversight on behalf of the Sponsor and Funder.

The BRITISH study have the involvement of Patient Participant Engagement (PPIE) throughout the life cycle of the study. PPIE were involved in the submission of the grant application and there is PPIE representation on the TSC and TMG. A PPIE group helped refine the BRITISH study patient facing documents. The group strongly supported the collection of the data for the purposes described above.

The UoS (via the University of Southampton Clinical Trials Unit [SCTU]) will transfer data to NHS England. The data will consist of identifying details NHS Number, Surname, Forename, date of birth and a unique person ID for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the mortality dataset to the UoS Clinical Trials Unit. 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.

The UoS will use the NHS England Data to raise data queries on the pseudonymised clinical trial database. The NHS sites will be contacted and asked to respond to the queries through the provision of follow up information relating to the death. The UoS will not provide the NHS sites with the date of death.

The Data will be stored on servers at the University of Southampton Clinical Trials Unit.

The University of Southampton Clinical Trials Unit (SCTU) uses offsite back-up services provided by the Isilon storage platform.

The Data will be accessed onsite at the premises of The University of Southampton Clinical Trials Unit and will also be accessed by authorised personnel via remote access.

The Controllers 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 the UK. The data will not leave UK at any time.

Access is restricted to employees of the University of Southampton Clinical Trials Unit who have authorisation from the University of Southampton Clinical Trials Unit Data Manager. Only relevant members of The University of Southampton Clinical Trials Unit can download NHS England Data from the relevant database.

The data received from NHS England will be held in the restricted area at the University of Southampton Clinical Trials Unit and linked to NHS England data via the study ID numbers. The statistics team will be the only ones who can link this pseudonymised data with the data from the database.

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

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Researchers from the University of Southampton Clinical Trials Unit will analyse the Data for the purposes described above.

The expected outputs of the processing will be:

• A report of findings to Data Monitoring and Ethics Committee (DMEC) throughout the study to include aggregate information on deaths.

• Presentations to cardiologists, British Heart Foundation, and patient groups and other relevant charities via private communication and/or via conferences and other media at the end of the study

• Publication of results of the study will be published in an academic journal (e.g., New England Journal of Medicine) at the end of the study

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

• Patient Information leaflets

• Participant newsletters

The expected target dates being 2029.

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.

The use of the data could:

• advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations such as those who are eligible for an insertion of an Implantable Cardioverter Defibrillator (ICD).

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

The study hypothesis is that the insertion of an Implantable Cardioverter Defibrillator (ICD), when determined by the presence of CMR-detected ventricular scar, will reduce all-cause mortality in patients with non-ischemic cardiomyopathy (NICM) with severely impaired left ventricular function (LVEF ≤35%) in the context of primary prevention.

If The BRITISH study find evidence to support it's hypothesis, this would stimulate a change in national and international guidelines with the potential to inform new NICE guidelines. It would also change guidelines around the indication for CMR in NICM - this would become a key test in the routine clinical care of these patients. It would be one of the first studies to demonstrate that an imaging test can lead to an improvement in prognosis.

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.

Yielded Benefits is not a requirement for new applications.