AspECT EXceL- Aspirin Esomeprazole Chemoprevention Trial- Consenting Subset of the Cohort

The University College London requires access to NHS England data for the purpose of the following Clinical Trial:

AspECT EXceL - Aspirin Esomeprazole Chemoprevention Trial – EXtension Long-term; for the definitive risks vs benefits.

AspECT EXceL is a phase 4 study that involves long term follow-up of individuals previously recruited into the AspECT trial. There are no further direct patient interventions required. This study aims to capture a single data snapshot.

As part of the original AspECT trial, participants were assigned to receive either:

1) Low dose oral Proton Pump Inhibitor (PPI) (Esomeprazole) and no aspirin

2) High dose PPI (Esomeprazole) and no aspirin

3) Low dose PPI (Esomeprazole) and aspirin

4) High dose PPI (Esomeprazole) and aspirin

Inclusion Criteria:

1. Participants recruited to the original AspECT trial.

2. AspECT participants who have signed an AspECT EXceL consent form or have the use of personal data covered by the Data Sharing Agreement (DSA) reference DARS-NIC-776114-J7Q9J (the Section 251 subset of the cohort)

3. Participants who have given consent to allow access to AspECT data or have access covered by DARS-NIC-776114-J7Q9J

Exclusion Criteria:

1. Participants who are alive and unable or unwilling to give consent to participate in AspECT Excel.

2. Participants unwilling to give consent to allow access to AspECT data and are not covered by DARS-NIC-776114-J7Q9J

3. Participants not included in the original AspECT trial

Primary Outcomes:

The primary composite endpoint is time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, whichever occurs first, between randomisation into AspECT and the single data capture of AspECT EXceL.

This will be analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all participantsin the intention-to-treat population.

Key Secondary Outcomes:

1. Effects of combined PPI and aspirin on each of the three components of the primary endpoint separately.

2. Time to progression to low grade dysplasia.

3. Death from oesophageal cancer.

4. New solid Gastrointestinal (GI) tumours.

5. COVID-19 related deaths.

6. The Charlson Comorbidity Index (CCI).

The primary composite endpoint in AspECT was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all participants in the intention-to-treat population. University College London now wish to follow up the same endpoints in AspECT trial participants in the AspECT EXceL study.

The data provided will be more accurate and complete than what can be obtained from hospital sites’ completion of Case Report Forms, which relies on medical records that are often outdated or missing as a result of patients having moved hospitals after the conduct of the original AspECT trial and restructuring of NHS Hospital Trusts. If the analysis confirms that aspirin and PPI use leads to lower rates of oesophageal cancer, this may lead to changes in NICE recommendations/ national guidelines for the use of these drugs in the prevention of oesophageal cancer which is more cost-effective for the NHS compared to the current standard for diagnosis, endoscopy, which often involves 1+ year waiting lists for patients.

The following NHS England Data will be accessed:

Civil Registrations of Death (CRD)- necessary to support the analysis of time to progression to oesophageal cancer and/or death against Aspirin and PPI use.

NDRS Cancer Consolidated Data Set- necessary to support the analysis of time to progression to oesophageal cancer against Aspirin and PPI use.

Medicines Dispensed in Primary Care- necessary to support the analysis of aspirin and PPI use for the prevention of oesophageal cancer.

The level of the Data will be:

• Identifiable

The Data will be minimised as follows:

• Limited to a trial- This subset of the cohort consists of 550 individuals who survived and regained capacity in order to provide informed patient consent to participate in the study.

• Limited to data from

- NHSBSA and NDRS Cancer Consolidated Data Set - 2017 to latest available

- CRD- Latest available

The University College London 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.

UCL has delegated responsibility for the overall management of AspECT EXceL in the Comprehensive Clinical Trials Unit (CCTU) based at the UCL.

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 the Cancer Research UK (CRUK). The funding is specifically for the trial described.

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

There are multiple clinical collaborators and Patient and public involvement (PPI) representatives involved in the management of the trial. They will not be involved with, or advise on data processing, but are likely to help interpret the aggregated results (with small numbers suppressed) for the purpose of the report.

The Oesophageal Patients Association (OPA) has worked with UCL to support the study throughout its duration, with 4 Patient and Public Involvement (PPI) members who bring broad experience to the PPI group.

UCL CCTU will transfer data to NHS England. The data will consist of identifying details specifically NHS Number, Date of Birth, Family Name, Gender and a Study ID for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the Civil Registrations Deaths, NDRS Rapid Cancer Registrations and Medicines Dispensed In Primary Care datasets to UCL..

The Data will

• contain directly identifying data items which are required for analysis purposes and a unique person ID which can be used to link the Data with other record level data already held by the recipient

The Data will be stored on servers at UCL.

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

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).

The Data will not leave England or Wales at any time.

Access is restricted to individuals within the CCTU at UCL who work on the AspECT EXceL trial.

Data will be accessed by an individual (the Chief Investigator) with an honorary contract with UCL. This individual will act as an agent of UCL at all times under supervision from employees of UCL. Aside from this individual, access is restricted to employees or agents of UCL who have authorisation from Principal Investigator.

Oxford Oncology Clinical Trials Office (OCTO (sponsor of original AspECT study) and hospital sites are 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 their data from the original AspECT study obtained from OCTO, in addition to AspECT ExceL trial data obtained from hospital sites.

The identifying details will be stored in a separate database to the linked dataset used for analysis.

The expected outputs of the processing will be:

• A single report of findings to CRUK, the trial funder, upon completion of the trial.

• Single submission to peer reviewed journals upon completion of the trial.

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

• Webinars

• Social media

• Public reports

• Industry newsletters

• Press/media engagement

• Public promotion of the research via journals or presentations

• Participant newsletters

The target period to produce these outputs will be soon after the results obtained from the analysis of the data has been completed, approximately August 2025.

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:

• 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 the need for, or effectiveness of, preventative health and care measures for the Barrett’s oesophagus patient population who are at risk of developing oesophageal adenocarcinoma.

• 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.

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

Specific benefits to patients expected are:

- What is the optimum dose, duration or age to begin aspirin therapy for the prevention of oesophageal cancer

- Prevent Barret’s patients that are often in 1+ years waiting lists for endoscopies (the current standard for diagnosis), from having undiagnosed and untreated oesophageal cancer for a long time.

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. E.g. for NICE to make national recommendations for the use of these drugs to prevent cancer.

CRUK has funded the study, the controller has provided regular updates on the study to CRUK. The controller will also generate a report of the study findings at the end of the study, which will support the findings from the original AspECT study which CRUK also funded.

Yielded Benefits is not a requirement for new applications.