SCOPE2 - A randomised Phase II/III trial to study radiotherapy dose escalation in patients with oesophageal cancer treated with definitive chemo-radiation with an embedded Phase II trial for patients with a poor early response using positron emission tomograph

The Cardiff University and the Velindre NHS Trust require access to NHS England data for the purpose of the following research project:

SCOPE2 - A randomised Phase II/III trial to study radiotherapy dose escalation in patients with oesophageal cancer treated with definitive chemo-radiation with an embedded Phase II trial for patients with a poor early response using positron emission tomograph.

The following is the summary of the aims of the clinical trial provided by the Cardiff University and the Velindre NHS Trust.

The SCOPE2 trial is a multicentre randomised study evaluating radiotherapy doses and chemotherapy combinations for oesophageal cancer. The study aims to determine whether a higher dose of radiotherapy improves survival rates and to assess the efficacy and toxicity of an alternative chemotherapy regimen in patients who do not respond to standard treatment.

Research has shown that increasing the dose of radiotherapy improves outcomes in patients with lung, head and neck cancers. This study aims to see whether this is also the case for patients with tumour of the oesophagus. This trial will compare the effects of the standard dose of radiotherapy to a higher dose whilst closely monitoring the side effects.

A comparison will also be made regarding the effects of the standard drugs used in chemotherapy (cisplatin and capecitabine) with an alternative combination (carboplatin and paclitaxel) in patients that do not show a response to chemotherapy with standard drugs early on in treatment. If not responding, patients were randomised to either switch chemotherapy or continue with the same chemotherapy

To accurately assess the primary endpoints, including overall survival (OS) and 24-week treatment failure-free survival (TFFS), access to mortality data is required for participants who provided explicit consent for long-term follow-up.

SCOPE2 closed to recruitment on the 31st of January 2024. The trial recruited 439 participants, 428 of whom went on to be randomised.

The following NHS England Data will be accessed:

• Civil Registration Mortality – necessary to ensure the accuracy of primary endpoints, mortality data collection is required for SCOPE2 participants. Access to civil registration mortality data ensures all deaths are accurately reported and verified, improving the robustness and reliability of the trial’s findings.

The level of data will be:

Identifiable

Although the requested data will consist solely of pseudonymised fields, Cardiff University retain access to the corresponding identifiers. While no efforts will be made to reidentify participants, the technical capability to do so remains.

The Data will be minimised as follows:

• Limited to a study cohort of approximately 400 patients identified by the Cardiff University and who provided their consent for the trial.

The Velindre NHS Trust as the trial sponsors, and the Cardiff University as the main collaborator, 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.

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. The funding is specifically for the trial described. The funder will have no ability to suppress or otherwise limit the publication of findings

The SCOPE2 Trial Management Group (TMG) has always included PPI Research Partners who have given their views and input to the design of the trial from its conception through to its eventual closure and dissemination. The Research Partners have helped to write the Participant Information Sheets and given their input throughout each of the different versions. The request for mortality data from NHS England was verbally discussed with the TMG before an application was submitted and all are aware of the plans for collection of data using this method.

The Cardiff University will transfer data to NHS England. The data will consist of identifying details (specifically NHS number, Date of birth, first and last name, postcode and Study ID) for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the Civil Registration of Death datasets to the Cardiff University. 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 Data will not be transferred to any other location.

The Data will be stored on servers at Cardiff University with management oversight by the Centre for Trials Research (CTR) and Microsoft Azure Cloud.

Cardiff University uses an offsite back up services provided Microsoft Azure Cloud as well as local sites referred to as Cardiff University Backup 1.

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

Cardiff University 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/Wales at any time.

Access is restricted to employees of Cardiff University who have authorisation from the Principal Investigator.

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

The Data will not be linked with any other data.

Analysts/researchers from the University of Cardiff will process/analyse the Data for the purposes described above.

The expected outputs of the processing will be:

The report of the findings will be included in the final analysis, with aggregated (non-identifiable) data incorporated into the study’s results.

Verification of death records to ensure the integrity of the data used for the final analysis. The received mortality data will be cross-checked against case report forms submitted by sites to ensure accuracy

The processed data will inform the final study publication, ensuring reliable reporting of outcomes.

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:

• Medical Journals

• Public events such as the medical meetings

• CTR website ((https://www.cardiff.ac.uk/centre-for-trials-research) accessible the general public

It is hoped the main publication will be made by June 2026 but this might change depending on the event rate and decisions by the Independent Data Monitoring Committee (IDMC).

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 data will verify information which contributes to the primary endpoint of the trial. Without accurate assessment of the event rate, the SCOPE2 trial may not be able to robustly answer the research question it was designed for. We expect this to be done in early 2026 as part of the final analysis.

This data request will show how robust our data checks and methods of communication have been in obtaining accurate data. This learning will be vital when embarking upon future trials.

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.